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Sample records for phys stat sol

  1. Preface: phys. stat. sol. (a) 202/12

    NASA Astrophysics Data System (ADS)

    Neumann, Wolfgang; Stutzmann, Martin; Hildebrandt, Stefan

    2005-09-01

    The present special issue contains a collection of Original Papers dedicated to Professor Johannes Heydenreich on the occasion of his 75th birthday.Johannes Heydenreich, born on 20 June 1930 in Plauen/Vogtland near Dresden, studied physics at the Pädagogische Hochschule Potsdam, where he obtained his first academic degree Dipl. Phys. in 1958. He received his doctoral degree at the Martin Luther University in Halle in 1961 and the Habilitation degree in 1969. Already during his studies in Potsdam, he showed an interest in electron microscopy due to the influence of his teacher and supervisor Prof. Picht, one of the pioneers in electron optics. His interests were strengthened when Johannes Heydenreich did the experimental work for his Diploma degree at the Institute for Experimental Physics of the University of Halle, where he met Prof. Heinz Bethge for the first time. This was the beginning of a fruitful and longstanding collaboration. In 1962 Johannes Heydenreich joined the team of the later Institute for Solid State Physics and Electron Microscopy of the Academy of Sciences of the GDR, in Halle, for which the basis was laid by Prof. Bethge in 1960.Heydenreich has been working as Assistant Director for many years and played a decisive role in introducing and organising the various techniques of electron microscopy in the institute.The research activities of Prof. Heydenreich covered a broad spectrum over the years. At the beginning of his career he made significant contributions in the field of electron mirror microscopy. After that, his main interests were focused on transmission electron microscopy, ranging from diffraction contrast analysis of crystal defects to high-resolution electron microscopy and image processing. His favourite field was studies of defect-induced phenomena in advanced materials. The so-called Bethge-Heydenreich, the book Electron Microscopy in Solid State Physics, published at first in a German edition in 1982 and later in a revised

  2. Preface: phys. stat. sol. (c) 1/9

    NASA Astrophysics Data System (ADS)

    Leitch, Andrew; Botha, Reinhardt

    2004-08-01

    The Conference on Photo-responsive Materials took place at the Kariega Game Reserve in the Eastern Cape, South Africa from 25-29 February 2004. More than 60 delegates from 12 different countries participated in the four-day event.The purpose of the conference was to bring together scientists working on various aspects of photo-responsive materials, so as to stimulate this important field of solid state physics in Southern Africa. As may be seen from the list of papers appearing in these proceedings, there was much interest in copper indium diselenide as a thin film material for photovoltaic applications. Also worth mentioning were the valuable contributions on ZnO, GaN and other materials that are currently attracting attention worldwide.The conference program allowed sufficient time for interaction and exchanging of views. Being in a game reserve in the heart of the beautiful Eastern Cape, delegates were also taken on game drives and had the opportunity of taking a river cruise up the Kariega River to view the majestic fish eagle.The members of the academic program committee were: Vivian Alberts (Rand Afrikaans University), Danie Auret (University of Pretoria), Darrell Comins (University of the Witwatersrand), and Reinhardt Botha and Andrew Leitch (University of Port E All papers appearing in these proceedings underwent a strict reviewing process separate from the conference. We express our appreciation to the referees for their diligence in this important task. The conference was organized by the Department of Physics at the University of Port Elizabeth, under the auspices of the Condensed Matter Physics and Materials Science (CMPMS) subgroup of the South African Institute of Physics. It was sponsored by EMF Limited (UK), Sensors Unlimited Inc. (USA), and Carl Zeiss (Pty) Ltd. Special thanks must go to Dr Eunete van Wyk for her professional assistance in the preparation of these proceedings.

  3. Preface: phys. stat. sol. (b) 242/9

    NASA Astrophysics Data System (ADS)

    Sánchez, Maria

    2005-07-01

    The XVII Latin American Symposium on Solid State Physics took place in the conference rooms of the Convent San Francisco de Asis, in the heart of the Old Havana. The sixteen previous editions were organized in eight different countries; the last two were in Colombia (Cartagena, 1999) and Venezuela (Merida, 2002). After eighteen years the meeting came back to Havana in 2004.The program topics included: Surfaces and interfaces analysis; Spintronics; Magnetism; Materials and energy; Ab-initio methods, simulations and modeling in solids; Nanophysics, nanomaterials and nanotechnology; New materials, properties and applications; Preparation of materials, thin films and characterization; High temperature superconductivity; Techniques of structural analysis in solids. The program included 6 plenary talks, 13 invited talks, 58 oral presentations (in eight sessions) and 200 poster contributions (in four poster sessions).The meeting attracted more than 200 participants from 14 countries. The physica status solidi Young Researcher Award sponsored by Wiley-VCH was conferred at the meeting. This prize was divided between two participants: Clara Calderón (Study of electrical transport properties of ZnO thin films used as front contact of solar cells) from Colombia and Aim?? Pelaiz Barranco (AC behavior in lanthanum modified PZT ferroelectric ceramics) from Cuba. Special Mentions went to Val??rie Halté (Femtosec-ond dynamics of transmission of gold arrays of sub-wavelength holes) from France, Erick Larramendi Cancio (Cd desorption induced by Zn exposure during atomic layer epitaxy of CdxZn1-xTe) and Julio Cesar Rimada Herrera (Quantum and conversion efficiency calculation of AlGaAs/GaAs multiple quantum well solar cells) from Cuba.Nanostructures and in general low dimensional physics related to different systems was a very hot topic during the meeting. Some talks and presentations were devoted to optoelectronic materials and devices. Characterization of solids by different structural and optical techniques together with modeling and simulations were also important subjects of the symposium.The XVIII Symposium will be held in Mexico in 2006.The editors wish to thank all the participants who contributed to the success of the meeting and hope that it helped to develop close links between researchers and institutions of Latin America.

  4. Preface: phys. stat. sol. (b) 242/2

    NASA Astrophysics Data System (ADS)

    Szopa, Marek; Mierzejewski, Marcin; Lisowski, Mariusz

    2005-02-01

    This issue contains the Proceedings of the 28th International Conference of Theoretical Physics, ICTP2004 - Electron Correlations in Nano- and Macrosystems, which was held in Ustro, Poland, from 2-7 September 2004. ICTP2004 followed the series of conferences organized by the Institute of Physics of the University of Silesia in Katowice, devoted biannually to the physics of condensed matter.The main objective of the Conference was to bring together specialists working on the physics of electron correlations in nano- and macro-regimes, with the intention of enhancing their mutual understanding and cooperation. The Conference was an international forum for the presentation and discussion of novel scientific ideas and experimental results. The programme of the conference consisted of 25 invited lectures, 11 contributed lectures and 27 papers presented during poster session. The contributions were devoted to problems related to the following subjects: Transport in low dimensional systems Carbon nanotubes and fullerenes Non Fermi liquid systems Superconductivity and Magnetism Quantum phase transitions New materials in magnetoelectronics Among the participants were 88 scientists from 10 countries and 3 continents. The invited talks were presented by distinguished physicists: Hélène Bouchiat, Liviu Chibotaru, Ulrich Eckern, Klaus Ensslin, Jim Freericks, Raymond Frésard, Peter Hänggi, Heike Herper, Carsten Honerkamp, Helmut Keiter, Stefan Krompiewski, Tadeusz Lulek, Kazumi Maki, Nina Markovi, Roman Micnas, Volker Meden, Andrzej M. Ole, Thomas Pruschke, Marek Przybylski, Ken-ichi Sasaki, Uri Sivan, Józef Spaek, Frank Steglich, Michael Thorwart and Roland Zeyher. The Organizing Committee would like to express our gratitude to the International Scientific Committee and to all the speakers and contributors for their talks and posters. Special thanks are addressed to all the participants for their valuable discussions and stimulating atmosphere of the meeting. We express our thanks to the referees. Their work improved significantly the quality of papers presented in this issue. We are also indebted to the editorial staff of physica status solidi for their help. Our cooperation was smooth and efficient. Last but not least, we thank all the sponsors of the conference (see list).

  5. Preface: phys. stat. sol. (b) 241/10

    NASA Astrophysics Data System (ADS)

    Demkov, Alex; Gilmer, David; Liang, Yong; Fonseca, Leonardo; Liu, Chun-Li

    2004-08-01

    The following 15 papers were presented at the 5th Motorola Workshop on Computational Materials and Electronics held 13-14 November 2003 in Austin, Texas, USA . Not every talk given at the workshop is represented with a paper in this selection; however, the reader should be able to come up with a general picture and the scope of the workshop.Traditionally, the Motorola Workshop on Computational Materials and Electronics has covered materials theory, nano-device physics and semiconductor processing. The main focus of the 2003 Workshop was Alternative Gate Dielectrics for CMOS Technology. This year we again expanded the scope of the Workshop to include experiment, in addition to the computational materials, quantum transport, and molecular electronics. The participants came from fifteen US and one European university, four National Laboratories, International SEMATECH, and Motorola's Semiconductor and Corporate research organizations. The Workshop illustrates our continuing commitment to longer-term research, and to the research community. We hope you will enjoy the reading.

  6. Preface: phys. stat. sol (a) 203/9

    NASA Astrophysics Data System (ADS)

    Duewski, P.; Bristowe, P.; Maurice, J.-L.; Komninou, P.

    2006-07-01

    This special issue contains a selection of papers that were presented at a symposium on Interfacial Processes and Properties of Advanced Materials (IPAM05) held at the E-MRS Fall Meeting, Warsaw, Poland on 5-7 September 2005. The symposium was conceived and inspired by the success of its predecessor (IPAM04) held at the University of Caen, France in June 2004.The symposium attracted over sixty contributions and was organized around five areas: Interfaces and dislocations in compound semiconductors, Gate oxide interfaces, Interfaces and defects in electroceramics, Metal-metal interfaces and interfacial modeling, and Interfaces in nano-structured and amorphous thin-film systems. The focus was on the influence of buried interfaces on the functionality of various electronic and opto-electronic devices such as lasers, ferroelectric memories, CMOS and magnetic disks. Therefore the materials addressed at the symposium included compound semiconductors (e.g. GaN, CdTe, ZnO), perovskites (e.g. SrTiO3), dielectrics (e.g. HfO2, SiO2, Al2O3), and metals (e.g. Fe/V superlattices). The aim of the symposium was to bring together leading interface experts, both experimental and theoretical, to explore the connection between interfacial properties (atomic and electronic structure, segregation, diffusion, kinetics) and materials performance in a device application. Papers were presented that described the use of a variety of sophisticated experimental techniques to explore the interfacial properties including HRTEM, X-ray high-resolution diffraction, Raman spectroscopy, STM, AFM, PL spectroscopy, SIMS and electrical and magnetic measurements. The theoretical work included applications of density functional theory, atomistic simulations, dislocation theory and finite element modeling. The program stimulated many exciting and productive discussions between experimentalists and theorists. The ultimate objective was to improve our knowledge of the role of interfaces on the properties of current and emerging device materials. It is hoped that these proceedings represent a step towards that goal and will encourage further conferences in this area in the future.The organisers gratefully acknowledge funding from the US Office of Naval Research Global (ONRG) Conference Support Program. They also would like to thank E-MRS for their administrative support and the Institute of Physics, Polish Academy of Sciences and the Warsaw University of Technology for hosting the symposium.

  7. Preface: phys. stat. sol. (b) 242/13

    NASA Astrophysics Data System (ADS)

    Esser, Norbert; Zahn, Dietrich R. T.

    2005-11-01

    Wolfgang Richter celebrated his 65th birthday on 2 January 2005. On such an occasion, usually marking retirement, achievements and breakthroughs in research are reviewed. But Wolfgang Richter is not retiring: he has accepted an offer of a professorship at the University Rome II Tor Vergata. As he explained to us with his famous smile, he plans to concentrate his future efforts even more on his true love in science - the optical diagnostics of interfaces.Wolfgang Richter has been working in the field of optical spectroscopy of solids since his PhD studies at the University of Cologne. Having finished his PhD in 1969 in the field of infrared spectroscopy he decided to reduce the probed volume by increasing the energy of probing photons: Raman spectroscopy! During his postdoctoral and Habilitation periods (1970-1979) at Pennsylvania State University, Max-Planck-Institut für Festkörperforschung, and RWTH Aachen, he pursued his interest in resonance Raman spectroscopy on semiconductors.In 1979 he received his first appointment as full professor at the University of Ulm. He returned to RWTH Aachen in 1981 and discovered his true destiny: semiconductor interfaces. At that time in the Department of Semiconductor Technology, metal-organic vapour phase epitaxy (MOVPE) was under development as a new technique for growing semiconductor layers. The underlying processes in MOVPE were known to be complex and very difficult to analyse with available experimental techniques, due to the unfriendly, reactive gas phase environment. Optical diagnostics turned out to be the key to a better understanding of MOVPE processes. Wolfgang Richter moved from RWTH Aachen to TU Berlin at the end of 1988 and began building a strong research group concentrating on interface analysis from two complementary sides: on the one hand, tracking MOVPE growth processes online by in situ optics and, on the other hand, advancing the fundamental understanding of optical spectra of interfaces by relating the optical response to atomic structures. Combining both aspects has finally led to considerable progress in surface and interface optics, as well as in vapour phase epitaxy and, moreover, the in situ optical tools developed are nowadays available as standard options in commercial MOVPE machines.The advances largely concerned the development of reflectance anisotropy spectroscopy and spectroscopic ellipsometry as in situ optical tools. However, considerable progress in Raman spectroscopy was also made: analysis of surfaces, ultrathin layers down to a single monolayer or even sub-monolayer coverages, and sub-wavelength spatial resolution were demonstrated in recent years. Current challenges concern, in particular, organic materials, molecule-solid interfaces and bio-interfaces, which will help in the development of many new applications and devices. Interfaces will play a crucial role in many of these developments and optical spectroscopy offers promising capabilities for analysing such interfaces. Wolfgang Richter and his group at University of Rome II Tor Vergata are sure to be active in this emerging field for a long time to come.Based on a symposium on Optical Spectroscopy of Interfaces at the Spring Meeting of the German Physical Society in Berlin 2005, we have asked former and present colleagues of Wolfgang Richter to contribute to this special issue of physica status solidi (b) on Advanced Optical Diagnostics of Surfaces, Nanostructures and Ultrathin Films. We think that the collection of 26 papers gives an excellent overview on recent achievements and future developments in the field of linear optics. In addition to a number of Original Papers on experimental work and some Review Articles, the issue includes examples of the current approaches of computational theory to solid state optics and interface optics. We hope that this issue will stimulate the expansion of the growing field of optical analysis of interfaces, nanostructures and ultrathin layers into new areas of basic and applied science. After the success in characterising inorganic materials, it is surely time that the potential of optical spectroscopy techniques for probing thin films and interfaces of composite (organic-inorganic) materials was considered.5 October 2005

  8. Editorial: phys. stat. sol. (a) 201/5

    NASA Astrophysics Data System (ADS)

    Stutzmann, Martin

    2004-04-01

    Physica status solidi was founded in 1961 by a number of eminent solid state physicists as an attempt to overcome the iron curtain, which then separated East and West, at least in the field of science. Since that time our world has changed quite a bit, and so have the boundary conditions of science publishing. However, one thing has not changed: then as now, the general policy and development of a respectable scientific journal should be determined by a board of independent scientists, who volunteer to assume responsibility for the scientific content of the journal, to assure a fair and critical peer review process for all submitted manuscripts, and, in cases of conflict, to finally decide which papers will be published and which will not.As a matter of fact, an international Board of Editors which consists of scientists coming from different countries and continents, with a good reputation in their respective community, and without any conflict of interest with the Publisher of the journal is, in my opinion, these days more important than ever. As our daily scientific work becomes increasingly specialized, but at the same time also increasingly interdisciplinary, we are more and more forced to trust the quality and reliability of published scientific results in the literature, without really having a chance to come to an independent opinion on our own. This is one of the reasons why the many recent cases of plagiarism, scientific misconduct, or outright fraud have caused such a high level of public awareness. It is quite clear that without a serious peer review there would be an even larger number of such cases in the literature, and that without the responsible action taken by concerned Journal Editors, many of the revealed cases probably would have remained under the carpet.It is, therefore, a particular pleasure for me to introduce to you on the following pages the current Editorial Board of physica status solidi (a) in the form of a brief curriculum vitae, a photograph, and an e-mail address (in case you want to contact our Editors directly!). Of course, since 1961 the Editorial Board of our journal has undergone many changes and will continue to do so, but we always have attempted to maintain a good balance between the different areas of solid state physics, between theory and experiment, and between different countries. And although nothing is perfect, I hope that you will find at least one or two board members, who are known to you through their contributions to the literature in solid state physics.For me, this is the perfect occasion to thank all Members of the Editorial Board, past and present, for their advice, continuing support, and dedication! Vielen herzlichen Dank!

  9. Editorial: phys. stat. sol. (b) 241/5

    NASA Astrophysics Data System (ADS)

    Stutzmann, Martin

    2004-04-01

    Physica status solidi was founded in 1961 by a number of eminent solid state physicists as an attempt to overcome the iron curtain, which then separated East and West, at least in the field of science. Since that time our world has changed quite a bit, and so have the boundary conditions of science publishing. However, one thing has not changed: then as now, the general policy and development of a respectable scientific journal should be determined by a board of independent scientists, who volunteer to assume responsibility for the scientific content of the journal, to assure a fair and critical peer review process for all submitted manuscripts, and, in cases of conflict, to finally decide which papers will be published and which will not.As a matter of fact, an international Board of Editors which consists of scientists coming from different countries and continents, with a good reputation in their respective community, and without any conflict of interest with the Publisher of the journal is, in my opinion, these days more important than ever. As our daily scientific work becomes increasingly specialized, but at the same time also increasingly interdisciplinary, we are more and more forced to trust the quality and reliability of published scientific results in the literature, without really having a chance to come to an independent opinion on our own. This is one of the reasons why the many recent cases of plagiarism, scientific misconduct, or outright fraud have caused such a high level of public awareness. It is quite clear that without a serious peer review there would be an even larger number of such cases in the literature, and that without the responsible action taken by concerned Journal Editors, many of the revealed cases probably would have remained under the carpet.It is, therefore, a particular pleasure for me to introduce to you on the following pages the current Editorial Board of physica status solidi (b) in the form of a brief curriculum vitae, a photograph, and an e-mail address (in case you want to contact our Editors directly!). Of course, since 1961 the Editorial Board of our journal has undergone many changes and will continue to do so, but we always have attempted to maintain a good balance between the different areas of solid state physics, between theory and experiment, and between different countries. And although nothing is perfect, I hope that you will find at least one or two board members, who are known to you through their contributions to the literature in solid state physics.For me, this is the perfect occasion to thank all Members of the Editorial Board, past and present, for their advice, continuing support, and dedication! Vielen herzlichen Dank!

  10. Preface: phys. stat. sol. (a) 203/4

    NASA Astrophysics Data System (ADS)

    Kittler, Martin; Yang, Deren

    2006-03-01

    This issue of physica status solidi (a) contains the majority of papers presented at the 2nd Sino-German Symposium The Silicon Age which was held at the Lindner Hotel Cottbus, Germany, 19-24 September 2005. This meeting followed the 1st Symposium Progress in Silicon Materials held in June 2002 in Hangzhou, P.R. China. 8 Chinese and 14 German scientists from universities, research institutes and industry were invited to present their views about different aspects of silicon.There was a continuous progress in silicon materials development during the last 40-50 years, driven by the need of the IC industry for better and larger monocrystalline silicon wafers. Moreover, low-cost crystalline silicon now dominates the world's production of solar cells in the photovoltaics industry. Furthermore, there are intensive research activities worldwide for on-chip integration of Si-based photonics in CMOS technology. In addition, new areas being connected with silicon are starting to appear, namely Si-based biochips and nanoelectronics. Silicon, one can reasonably argue, is already the most investigated of all materials. However, there is still a need for continuation of research and development regarding numerous aspects of Si and also SiGe, including related technologies, advanced diagnostics or the role of crystal defects, which are the working fields of many laboratories all over the world. This was also shown by the presentations at the symposium and can be found in the contributions contained in this issue.The organizers would like to thank the participants for their high level contributions and discussions during the symposium. This intensive and open communication allowed the participants to create synergies between the different fields of silicon research and also to build up relationships for cooperation between Chinese and German research groups.Finally, we would like to thank the Sino-German Science Center for the financial support of the symposium.

  11. Preface: phys. stat. sol. (c) 1/7

    NASA Astrophysics Data System (ADS)

    Cheikhrouhou, Abdelwaheb

    2004-05-01

    The Third International Conference on Magnetic and Superconducting Materials (MSM03) belongs to a series of conferences, held biannually, aiming at providing a forum to the scientists in the magnetic and superconducting materials areas over the world.The first conference of the series (MSM99) was held in Iran with the proceedings published by World Scientific in 2000, and the second conference (MSM01) was held in Jordan with the proceedings published in Physica B 321 (2002).MSM03 was organized by the Materials Physics Laboratory, Sfax University (Laboratoire de Physique des Matériaux de la Faculté des Sciences de Sfax), with many domestic and international supporting institutions. It was held in Monastir (Tunisia), 1-4 September 2003, with over 150 participants and keynote lecturers attending from the following countries: Algeria, Austria, China, Czech Republic, Egypt, France, Germany, Hungary, Iran, Italy, Japan, Jordan, Morocco, Netherlands, Pakistan, Poland, Russia, Spain, Sudan, Sultanate of Oman, Taiwan, Tunisia, United Kingdom and United States of America.Altogether, about 170 papers on a variety of subjects relevant to the topic of the conference were presented, out of which 42 were keynote lectures. The submissions were peer-reviewed, and ultimately 115 articles were selected for publication in this journal. However, it must be noted that 13 of 39 keynote speakers did not submit their manuscripts for publication. Invited and other speakers were distinguished members of the international scientific community who are interested in pure sciences and materials research, and involved in the fabrication, characterization and investigation of the physical properties of magnetic and superconducting materials. High-caliber scientists attended the conference contributing to its success and the event resulted in new international relationships in research and cooperation. The Chairman of the Organizing Committee was Professor Abdelwaheb Cheikhrouhou, Materials Physics Laboratory, Sciences Faculty of Sfax (Tunisia) and the Co-Chairmen were Professor Sami Mahmood, Dean of Sciences at Yarmouk University (Jordan) and Professor Mohamed Akhavan from the Sharif University of Technology (Iran). The four-day conference consisted of several oral and poster sessions, followed by social programs in the evenings. The success of the event could be measured during the closing session on the last day, when several delegates emphasized the high-quality science that had been evident at the conference. A post conference three-day tour to the south of Tunisia (Matmata, Douz City: the gate of desert and the mountains oasis: Tamerza, Mides and Chebika) was also arranged. The conference was generously sponsored by: - The Tunisian Ministry of High Education, Scientific Research and Technology - The Tunisian Secretary of State for Scientific Research and Technology - The Tunisian National Office of Tourism - The Abdus Salam International Centre for Theoretical Physics (ICTP) - French Institute for Cooperation in Tunisia - Tunisian-Italian Scientific Partnership - British Gas - Tunisian Society for Electricity and Gas - Imex Olive Oil -Confiserie TRIKI Le Moulin The next MSM conference in 2005 will be held in Morocco.

  12. Preface: phys. stat. sol. (b) 241/9

    NASA Astrophysics Data System (ADS)

    Morawetz, Klaus

    2004-07-01

    Modelling and Simulation in Molecular Systems, Mesoscopic Structures, and Material Science was the title of a workshop held at the University of Technology in Chemnitz from 21 to 23 April 2004. This workshop coincided with the 50th birthday of Michael Schreiber. Therefore, the idea to publish a special issue is supported by two good reasons. First, a topical collection is appropriate for giving an overview about a field and to initiate further studies. This is one intention of the present issue. Second, the birthday is a suitable occasion for reflecting on the status of the different fields where Michael Schreiber has been active himself. Motivated by the characteristic name of the workshop (MS4), which expresses the broad range of his activities, the contributions are grouped into three main chapters: Disorder and Interaction, Phase Transitions and Criticality, and Transport Properties.The first part starts with the currently intensively discussed topic of composite Fermions in the paper by B. Kramer et al. This method of rewriting correlations as new quasiparticles has amongst other things the merit of explaining such exciting phenomena as the fractional quantum Hall effect. The methodological questions of Ward identities, causality, and conservation laws are the focus of the systematic investiga-tion in the second article by V. Janis et al. which concentrates on the problem of disorder and configura-tional averaging. The interplay between disorder and correlation is treated in the third contribution by C. Schuster et al., where different theoretical methods are tested on the problem of Friedel oscillations within the one-dimensional Heisenberg and Hubbard model. In the next contribution, M. Berciu et al. focus on localization as one consequence of disorder. The localized and extended electronic states are treated, together with the magnetic degrees of freedom, like spin waves. One of the astonishing consequence of localiza-tion is the observation of resonant Rayleigh backscattering. This is investigated by random matrix theory in the next article by E. Runge et al. and extended to exciton transitions in semiconductor nanostructures. In order to characterize localization, A. Eilmes et al. consider the two-dimensional Anderson model in the following article with special focus on the critical exponents for the localization length. The chapter on disorder ends with a contribution by A. Aldea et al. where the disorder effects are investigated in twodimensional systems with perpendicular magnetic fields such that the interplay between Landau levels and localized states can be considered.The second chapter in the collection is devoted to critical phenomena and phase transitions. It starts with an overview of the most prominent example of critical phenomena, high-Tc superconductivity. A. Sherman presents a review on magnetic and spectral properties of cuprate perovskites within t - J models. The long-range hopping problem and the extraction of critical exponents are the topic of the contribution by E. Cuevas, who calculated the level spacing distribution as well as the correlation dimen-sion in the strong coupling limit. The critical points and the thermodynamics of quenched spatial disordered systems are then treated by T. Vojta et al. Here it is shown that different parts of a system might undergo phase transitions controlled by different parameter values. Different microstructures are important when phenomena like the growth of crystals are considered. Consequently the latter problem is treated in the next contribution by H. Emmrich et al., who develop an analytical solution and compare it to simulations in order to provide insights into the universality of diffusion-limited crystal growth. That the applications of critical phenomena are quite versatile is demonstrated in a short paper by J. Stäring et al. who show how statistical methods can be employed to optimize networks of wireless communication. This chapter on critical phenomena ends with a methodological investigation by U. Grimm. This concerns the often applied random matrix theory, and a method to calculate the level spacing distribution by using coupled differential equations.The third chapter is devoted to transport. It starts with an article about conductance fluctuations by M. Ortuno et al. These quantum fluctuations are considered in localized systems which is directly related to the topics in the first chapter. M. Schröder et al. present in the next article a method to propagate wave functions by approximating them by multi-dimensional wave packets. In contrast to variational methods, this method is based on stochastic calculus. In the case where only a few electrons are transferred, as in the reaction of donor-acceptor complexes and molecular wires, a unified description is presented in the contribution by V. May et al. The transfer rate and the stationary current are calculated and their depend-ence on the length of the molecular system is shown. The method of Green's functions based on local orbitals is used in the next article by M. Albrecht et al. to calculate molecular charge transport. This results into a Landauer theory for the calculation of the transmission coefficient. The special role of elec-tron-electron interaction in the transport properties of disordered wires is considered by H. Mori et al. Here the interplay of interaction and disorder is investigated and the different roles of interaction for the localization phenomena are discussed. We close this chapter on transport by an investigation of electronic transport through nanoparticle arrays. The self-assembled nanoparticle structures are considered within the contri-bution by K. Nicolic whose structures represent very promising nanoelectronic devices.The broad-range approaches and applications selected in these three chapters demonstrate the exciting interplay between structure, disorder, and correlations and suggest the kind of future developments which are to be expected within this field. Finally, in the name of all authors and workshop participants: Happy birthday to Michael Schreiber and all best wishes for exciting future scientific activities!

  13. Preface: phys. stat. sol. (c) 1/6

    NASA Astrophysics Data System (ADS)

    Kavokin, Alexey

    2004-04-01

    This volume contains some of the papers presented at the Third International Conference on Physics of Light-Matter Coupling in Nanostructures (PLMCN3) which took place in Acireale, Sicily, from 1 to 4 October 2003. This meeting was fourth in the series started by PLMCN (St. Nectaire, 2000) and continued by PLMCN1 (Rome, 2001) and PLMCN2 (Rithymnon, 2002). All four conferences had the same format (about 70 participants), similar subject scope (interface between fundamental physics of light-matter coupling phenomena and applied research on new semiconductor materials and low-dimensional structures), and the proceedings of all of them have been published in physica status solidi.During these four years, a huge progress has been achieved in the understanding of exciton-polariton effects in microcavities. From the discovery of stimulated scattering of polaritons in 1999 to the first experimental reports of polariton Bose condensation and lasing, attention to this rapidly developing research area has been increased drastically. It is clear now that realization of a new generation of opto-electronic devices, referred to as polariton devices, is a realistic task for the coming decade. To achieve this target, much work has to be done both in fundamental research on dynamics of exciton-polaritons in microcavities and experimental realization of high-quality microcavities presumably based on wide-band gap semiconductors like GaN, ZnO, ZnSe, suitable for the observation of strong exciton-light coupling at room temperature. Forty nine research teams from twelve European countries have created a Polariton Consortium aimed at integration of the European research effort towards fabrication of polariton devices. PLMCN3 was not only an international conference devoted, in particular, to the research on polariton devices, but also the first scientific meeting of this community.The PLMCN meetings since the very first one have been sponsored by the US Army European Research Office (ERO). This time, with the initiative of Jim Harvey from ERO, a special session has been organized on the devices of 21st century, where a number of intriguing ideas have been proposed on new light sources, polariton lasers, and quantum memory elements based on microcavities. A special prize for the most crazy but realizable idea has been won by Misha Portnoi (Exeter) for the concept of a white diode based on a microcavity.Each PLMCN meeting brings participants from new countries. This time, the traditionally strong participation from Japan, Russia, the European Union and the USA has been enforced by a representative delegation from Israel and two speakers from Mexico. We are looking forward for new-comers from other countries not yet involved in the PLMCN community, to join us for the next meeting to be held in St. Petersburg on 29 June-3 July 2004. Sergey Ivanov from the A. F. Ioffe Institute chairs the local Organizing Committee of this future conference. We are going to keep a unique informal and creative atmosphere being characteristic of the PLMCN meetings. We invite all those who wish to know more about light-matter coupling in solids or to present any new interesting results in this area and at the same time to enjoy the beautiful city of St. Petersburg, to contact Sergey Ivanov (ivan@beam.ioffe.rssi.ru) or myself (kavokin@lasmea.univ-bpclermont.fr). We are looking forward to welcoming you in St. Petersburg!

  14. Preface: phys. stat. sol. (a) 201/11

    NASA Astrophysics Data System (ADS)

    Goovaerts, Etienne; Nistor, Sergiu V.

    2004-09-01

    We are glad to introduce in this issue of physica status solidi (a) a series of papers which were presented at the international workshop on Defects and Impurities in Crystalline Boron Nitride Compounds, held in Diepenbeek-Hasselt, Belgium, on 20-21 February 2004. Because of the strong scientific connections, this workshop was jointly organised with the 9th International Workshop on Surface and Bulk Defects in CVD Diamond Films (18-20 February 2004) and this led to the joint publication of the contributions in the present issue. For several years boron nitride, and in particular cubic boron nitride, is back in the centre of materials research activities because of new potential applications as a wide band gap semiconductor for electronics and opto-electronics in extreme conditions. However, important efforts are needed to understand the role of defects and impurities in controlling its semiconducting properties and growth processes in order to realise these promises. An international group of researchers (30 participants from 12 countries: Belarus, Belgium, Czech Republic, Germany, Italy, Japan, Latvia, Romania, Russia, Sweden, Ukraine, USA; among which 8 invited) has gathered to discuss the present status of research on the following topics: Impurities and morphology, Synthesis and microstructure, Optical and electrical properties, and Point defects characterisation. Contributions were presented on boron nitride single crystals, on p-n junctions formed with this material, but also on crystalline powders, thin films and B-C-N nanotubes. Among the characterisation methods which have been discussed, we mention optical spectroscopy (absorption, luminescence, Raman), multifrequency electron spin resonance, high resolution and analytical electron microscopy and analytical micro ion beam techniques.This workshop was organised as a final activity of the Flemish-Romanian scientific and technological cooperation project Defects in diamond-like materials of the B/C/N system, involving from the Flemish side both the Experimental Condensed Matter Physics Laboratory at the Physics Department of the University of Antwerp and the Materials Physics Division at the Institute for Materials Research of the Limburgs Universitair Centrum, and from the Romanian side the Microstructure of Defects in Solids Laboratory of the National Institute for Materials Physics in Magurele-Bucuresti.We gratefully acknowledge the financial support of the Flemish and Romanian governments through the above mentioned international bilateral project, as well as the organisational support of all three home institutions along the duration of the whole project.We also wish to personally thank Miloš Nesládek and Ken Haenen for the invaluable and continuous assistance in the practical organisation of this workshop.

  15. Preface: phys. stat. sol. (a) 201/5

    NASA Astrophysics Data System (ADS)

    Avelino Pasa, André

    2004-04-01

    This issue contains scientific contributions to the 4th German/Brazilian Workshop on Applied Surface Science. The workshop was held in Germany at the beautiful Castle Ringberg conference site of the Max Planck Society, located 60 km from Munich, from 21-26 September 2003. The meeting was attended by about 50 participants, with 21 invited talks and 18 contributed presentations (8 oral and 10 posters) on relevant topics of surface science.As in previous meetings (1995 in Portobello, RJ, Brazil, 1998 in Döllnsee, Berlin, Germany, and 2001 in Itapema, SC, Brazil), a significant number of important questions in surface science were covered from both the theoretical and the experimental point of view. In the field of materials science, emphasis was given to the description of the structural, physical and chemical properties of nanostructures and films of inorganic (metals, alloys and oxides) and organic (polymers and biological molecules) materials.A substantial part of the success of the meeting can be attributed to the relaxed atmosphere at the castle, near the lake Tegernsee, where excellent scientific presentations were mixed with intense discussions among both senior and younger researchers. The event also led to the development of new and ongoing collaborations between partners from Brazil and Germany.The organizers of the Workshop, Israel J. R. Baumvol (Porto Alegre, Brazil), Hajo Freund (Berlin, Germany), Wolfgang H. P. Losch (Natal, Brazil), Horst Niehus (Berlin, Germany), André A. Pasa (Florianópolis, Brazil) and Eberhard Umbach (Würzburg, Germany), are greatly indebted to the following organizations for financial support: Deutsche Forschungsgemeinschaft (DFG), Fritz-Haber-Institut Berlin (FHI), Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Universidade Federal de Santa Catarina (UFSC) and the specially created intergovernmental agreement between CAPES and DFG to promote such meetings.

  16. Editorial: phys. stat. sol. (b) 243/1

    NASA Astrophysics Data System (ADS)

    Stutzmann, Martin

    2006-01-01

    Dear Colleagues and Friends,on behalf of the Publishers, the Editorial Office, and the Editors of physica status solidi we wish you all the best for the coming year 2006! It is our sincere hope that your personal and professional experience with our journal has been a positive one and that you will continue to choose physica status solidi for the publication of your scientific findings in solid state physics also in the future.In doing so, you will be in increasingly good company! As a matter of fact, 2005 has been a year of exceptional growth in the number of manuscripts submitted to physica status solidi . Thus, the number of Original Papers which have reached our Editorial Office in Berlin has increased by as much as 30% compared to the long term average over the last ten years. For the Rapid Research Letter section, the corresponding increase has been even more impressive: more than +100% just in the last two years. We view this development as a confirmation of our longstanding efforts to ensure a timely publication service of high scientific quality. One relevant indicator for the high scientific standards expected from articles which are submitted for publication in physica status solidi is the average acceptance rate, which currently is less than 40%. This rate has continuously decreased from a value of about 60% ten years ago and bears witness to our efforts to strive for quality rather than quantity.Also, physica status solidi has been able to continue its long tradition as a truly international journal, despite of the strong competition in an established field such as solid state physics. In 2005, submitted papers have originated almost equally from the Americas, Europe, and Asia, with a clearly growing contribution from China, India, and Japan. We are actively working together with our international Editorial Boards and the Regional Editors to maintain a reasonable balance among papers from different parts of the world. The increasing international visibility of physica status solidi is impressively documented by the ever rising numbers of article downloads via the internet: on the average, each of the 2000 articles published annually in physica status solidi is presently accessed about 100 times via the www.Finally, let me mention some other recent developments, which are not so directly visible from the outside. Thus, a new all electronic publishing system has become operative in our Berlin Editorial Office in 2005, which allows a more efficient and timely handling of manuscripts from submission to publication (www.manuscriptXpress.com) and is particularly valuable for the editing of conference proceedings (conferences.wiley-vch.de). In addition, the functionality of the journal within the Wiley InterScience website has been enhanced by new features such as Citation Tracking. Together with the ongoing digitization of all physica status solidi issues since the 1960s, which is expected to be complete in 2006, this makes the physica status solidi homepage at Wiley InterScience a very valuable tool for literature search in solid state physics, past and present. Try it out at www.interscience.wiley.com!All of us from physica status solidi would like to convey to you our very best wishes for good health and success in the coming year 2006!

  17. Editorial: phys. stat. sol. (c) 3/1

    NASA Astrophysics Data System (ADS)

    Stutzmann, Martin

    2006-01-01

    Dear Colleagues and Friends,on behalf of the Publishers, the Editorial Office, and the Editors of physica status solidi we wish you all the best for the coming year 2006! It is our sincere hope that your personal and professional experience with our journal has been a positive one and that you will continue to choose physica status solidi for the publication of your scientific findings in solid state physics also in the future.In doing so, you will be in increasingly good company! As a matter of fact, 2005 has been a year of exceptional growth in the number of manuscripts submitted to physica status solidi . Thus, the number of Original Papers which have reached our Editorial Office in Berlin has increased by as much as 30% compared to the long term average over the last ten years. For the Rapid Research Letter section, the corresponding increase has been even more impressive: more than +100% just in the last two years. We view this development as a confirmation of our longstanding efforts to ensure a timely publication service of high scientific quality. One relevant indicator for the high scientific standards expected from articles which are submitted for publication in physica status solidi is the average acceptance rate, which currently is less than 40%. This rate has continuously decreased from a value of about 60% ten years ago and bears witness to our efforts to strive for quality rather than quantity.Also, physica status solidi has been able to continue its long tradition as a truly international journal, despite of the strong competition in an established field such as solid state physics. In 2005, submitted papers have originated almost equally from the Americas, Europe, and Asia, with a clearly growing contribution from China, India, and Japan. We are actively working together with our international Editorial Boards and the Regional Editors to maintain a reasonable balance among papers from different parts of the world. The increasing international visibility of physica status solidi is impressively documented by the ever rising numbers of article downloads via the internet: on the average, each of the 2000 articles published annually in physica status solidi is presently accessed about 100 times via the www. Finally, let me mention some other recent developments, which are not so directly visible from the outside. Thus, a new all electronic publishing system has become operative in our Berlin Editorial Office in 2005, which allows a more efficient and timely handling of manuscripts from submission to publication (www.manuscriptXpress.com) and is particularly valuable for the editing of conference proceedings (conferences.wiley-vch.de). In addition, the functionality of the journal within the Wiley InterScience website has been enhanced by new features such as Citation Tracking. Together with the ongoing digitization of all physica status solidi issues since the 1960s, which is expected to be complete in 2006, this makes the physica status solidi homepage at Wiley InterScience a very valuable tool for literature search in solid state physics, past and present. Try it out at www.interscience.wiley.com! All of us from physica status solidi would like to convey to you our very best wishes for good health and success in the coming year 2006!

  18. Editorial: phys. stat. sol. (a) 203/1

    NASA Astrophysics Data System (ADS)

    Stutzmann, Martin

    2006-01-01

    Dear Colleagues and Friends,on behalf of the Publishers, the Editorial Office, and the Editors of physica status solidi we wish you all the best for the coming year 2006! It is our sincere hope that your personal and professional experience with our journal has been a positive one and that you will continue to choose physica status solidi for the publication of your scientific findings in solid state physics also in the future.In doing so, you will be in increasingly good company! As a matter of fact, 2005 has been a year of exceptional growth in the number of manuscripts submitted to physica status solidi. Thus, the number of Original Papers which have reached our Editorial Office in Berlin has increased by as much as 30% compared to the long term average over the last ten years. For the Rapid Research Letter section, the corresponding increase has been even more impressive: more than +100% just in the last two years. We view this development as a confirmation of our longstanding efforts to ensure a timely publication service of high scientific quality. One relevant indicator for the high scientific standards expected from articles which are submitted for publication in physica status solidi is the average acceptance rate, which currently is less than 40%. This rate has continuously decreased from a value of about 60% ten years ago and bears witness to our efforts to strive for quality rather than quantity.Also, physica status solidi has been able to continue its long tradition as a truly international journal, despite of the strong competition in an established field such as solid state physics. In 2005, submitted papers have originated almost equally from the Americas, Europe, and Asia, with a clearly growing contribution from China, India, and Japan. We are actively working together with our international Editorial Boards and the Regional Editors to maintain a reasonable balance among papers from different parts of the world. The increasing international visibility of physica status solidi is impressively documented by the ever rising numbers of article downloads via the internet: on the average, each of the 2000 articles published annually in physica status solidi is presently accessed about 100 times via the www.Finally, let me mention some other recent developments, which are not so directly visible from the outside. Thus, a new all electronic publishing system has become operative in our Berlin Editorial Office in 2005, which allows a more efficient and timely handling of manuscripts from submission to publication (www.manuscriptXpress.com) and is particularly valuable for the editing of conference proceedings (conferences.wiley-vch.de). In addition, the functionality of the journal within the Wiley InterScience website has been enhanced by new features such as Citation Tracking. Together with the ongoing digitization of all physica status solidi issues since the 1960s, which is expected to be complete in 2006, this makes the physica status solidi homepage at Wiley InterScience a very valuable tool for literature search in solid state physics, past and present. Try it out at www.interscience.wiley.com!All of us from physica status solidi would like to convey to you our very best wishes for good health and success in the coming year 2006!

  19. Dedication: phys. stat. sol. (a) 202/15

    NASA Astrophysics Data System (ADS)

    Albrecht, Martin

    2005-12-01

    The papers in this issue are dedicated to Professor Horst Paul Strunk on the occasion of his 65th birthday and his retirement from active teaching. This volume honours a scientist who has made a lasting impact on the field in electron microscopic characterisation of growth and relaxation phenomena in epitaxial growth of semiconductors. Born in The Hague, The Netherlands, on 13 June 1940, he studied physics in Stuttgart where he received his degree in Physics in 1968. He joined the group of Prof. Seeger at the Max-Planck-Institut für Metallforschung and defended his Ph.D. on defects in NaCl at Stuttgart University in 1973. He spent one year at Cornell University as a visiting Professor before joining Technische Universität Hamburg-Harburg in 1983. There he created the Zentralbereich Elektronenmikroskopie and was a professor for materials analytics from 1983 till 1989. In 1989 he changed to the University of Erlangen-Nürnberg, where he established the Verbundlabor für hochauflösende Elektronenmikroskopie and directed the Lehrstuhl Mikrocharakterisierung at the Institut für Werkstoffwissenschaften of the same university. He spent two research periods at the Universities of Rennes in France and Campinas in Brazil. Together with his colleague Prof. Jürgen Werner he created the series of conferences on polycrystalline semiconductors POLYSE which he has been supervising together with Jürgen Werner since 1990.The research activities of Horst P. Strunk are focused on microstructure of materials and their relation to macroscopic physical properties. Main topics are dislocations, their formation and interaction mechanisms, strain relaxation as well as fundamental mechanisms of epitaxial growth. The spectrum of materials covers a wide range starting from metals over ionic crystals, e.g. NaCl to elemental and compound semiconductors. From the beginning, the main tool of study has been the transmission electron microscope. However, Horst P. Strunk recognised that a thorough understanding of materials problems would require the combined use of structural characterisation, advanced spectroscopy and modelling. Therefore he complemented electron microscopic approaches by optical methods e.g. Raman spectroscopy and cathodoluminescence. Modelling of strain states by finite elements and of defect structures by ab-initio calculations became an important topic especially in the last years. It is characteristic for the scientific approach of Horst Strunk that methodological developments were not an end in itself but linked to problems in solid state physics and materials sciences. Among the scientific works of Strunk, a few examples should be highlighted which mark important stages in his scientific career. Pioneering work has been done on the influence of dislocations in homoepitaxial growth of Si and GaAs in collaboration with Elisabeth Bauser in Stuttgart. Strunk correlated growth spirals on the surface to dislocations that caused these step sources. Studying the dislocation structure of heteroepitaxial Ge/GaAs layers, Strunk discovered that a new dislocation multiplication source works which, later known as Hagen-Strunk source, had a strong impact on understanding of relaxation processes by dislocations in heteroepitaxial semiconductor systems. Work on electrical and structural properties of grain boundaries in silicon was performed together with Jürgen Werner. This was the starting point of a long lasting research on photovoltaic materials that accompanies Strunk till today. Fundamental studies on heteroepitaxial growth were performed in the system SiGe grown from solution. In this context, finite elements were established for the first time in the study of nanostructured materials. In the last years correlated studies on structural and optical properties on III-nitride heterostructures were done by cathodoluminescence in the transmission electron microscope. The impact of Horst P. Strunk's work is evident from the fact that his lab became part of collaborative international projects based on the unique facilities at the Verbundlabor für Hochauflösende Elektronenmikroskopie and the profound knowledge in the field of crystal growth and solid state physics present in his group. The articles in this issue contain original research results contributed by his friends, collaborators and former students. They are a testimony of the lasting impact of Horst P. Strunk's work and they express the authors' gratefulness for benefiting from his work. This volume gives us a unique opportunity to say thank you to Horst P. Strunk and to wish him a new period in his life that should continue to be scientifically as fruitful as up to now but less affected by the burden of administrative work than during the last years.

  20. Preface: phys. stat. sol. (a) 203/12

    NASA Astrophysics Data System (ADS)

    Jackman, Richard B.; Nesládek, Milo; Haenen, Ken

    2006-09-01

    The 30 papers gathered in this issue of physica status solidi (a) give a thorough overview over different topics that were presented during the 11th edition of the International Workshop on Surface and Bulk Defects in CVD Diamond Films (SBDD), which took place from 22 to 24 February 2006, at the Hasselt University in Diepenbeek-Hasselt, Belgium. Since its start more than 10 years ago, the SBDD Workshop has grown into a well-established, yearly early bird meeting place, addressing new emerging science related to the progress in the CVD diamond field. The 10 invited lectures, 29 contributed oral presentations and 26 posters were presented in several sessions during an intense two and a half day long meeting.The number of participants reached 115 this year with participants coming from fifteen countries: Austria, Belgium, Czech Republic, France, Germany, Israel, Italy, Japan, Mexico, Poland, Russia, Singapore, Slovak Republic, Sweden, UK, and USA. The mixture of young and established scientists, including a great proportion of students, made this meeting a hot spot of lively discussions on a wide range of scientific subjects, not only during the meeting itself, but also at several occasions throughout many social events offered by the hospitality of the city of Hasselt.It stands for itself that the workshop would not have been possible without the support of many people and institutions. For financial aid we are especially indebted to the Scientific Research Community Surface Modification of Materials of the F.W.O.-Vlaanderen (Belgium), whose incessant support plays an important role in keeping this meeting going. We also thank the Hasselt University for offering the lecture hall and infrastructure facilities and Seki Technotron Corp. for sponsoring the poster reception and their presence with a table top exhibit. Finally we highly appreciate the active approach of the editorial staff of physica status solidi in this conference and would like to thank most notably Stefan Hildebrandt, Ron Schulz-Rheinländer, Christoph Lellig, and Julia Hübner, for their excellent and patient work, bringing the number of successfully published proceedings of SBDD in pss (a) up to 8 already!To finish, we would all like to invite you to the 12th edition of the SBDD series, newly renamed as Hasselt Diamond Workshop, to be held at its established location of Diepenbeek-Hasselt. We look forward meeting you again at SBDD XII in 2007:Hasselt Diamond Workshop - SBDD XII28 February-2 March 2007Hasselt University, Diepenbeek-Hasselt, Belgiumhttp://www.imo.uhasselt.be/SBDD2007London, Paris, Hasselt, August 2006

  1. Preface: phys. stat. sol. (a) 201/11

    NASA Astrophysics Data System (ADS)

    Bergonzo, Philippe; Haenen, Ken; Nebel, Christoph; Nesládek, Milo; Vanek, Milan

    2004-09-01

    The present issue of physica status solidi (a) contains a collection of 24 papers presented at the 9th International Workshop on Surface and Bulk Defects in CVD Diamond Films held in Diepen- beek-Hasselt, Belgium, 18-20 February 2004. The concept of this workshop originated in 1996 with the idea of bringing together scientists who are active and innovative in the field of electronic and optical properties of thin film diamond. Since then, this meeting have grown up to a regular conference devoted to new issues in CVD diamond research and related to diamond as a material for electronics and nanobioelectronics. This year the programme was spread over two and a half days, including 8 invited lectures from a total of 39 talks, and a poster session featuring 15 posters. In addition we were able to connect this meeting with a workshop on Defects and Impurities in Crystalline Boron Nitride Compounds, scientifically organized from the University of Antwerp and leading finally to a joint meeting lasting four days. The papers from the BN workshop are joining this proceeding issue on pages 2559-2598.At SBDD IX, topics ranged from homo- and heteroepitaxial growth, doping, hydrogen induced surface conductivity, defects and their characterization, to devices including bio-sensing applications. As usual, very intense and lively discussions took place among participants, from young students to established scientists, after talks, during breaks and in the evenings while enjoying the hospitality of the Limburgs Universitair Centrum and especially the city of Hasselt. The number of participants reached a record breaking 96 this year, with participants coming from fifteen different countries (Australia, Austria, Belgium, Czech Republic, France, Germany, Israel, Italy, Japan, Mexico, Romania, Russia, Sweden, UK, USA). This yearly increasing number indicates that this workshop is continuing to be very attractive to a large scientific community, as it summarizes the up-to-date research on diamond as a wide band gap semiconductor.The workshop would have not been possible without the support of many people and institutions. For financial aid we are especially indebted to the Scientific Research Community Surface Modification of Materials of the F. W. O.-Vlaanderen (Belgium) and its continuous support since starting this workshop 9 years ago. We also thank the Limburgs Universitair Centrum for offering the lecture hall and infrastructure facilities. Finally we highly appreciate the active approach of the editorial staff of physica status solidi in this conference and would like to thank most notably Stefan Hildebrandt and Katharina Fröhlich, for their excellent and patient work, making this already the sixth successfully published proceedings of SBDD in pss (a).To finish, we would all like to invite you for the 10th anniversary of the SBDD series in February 2005 in Diepenbeek-Hasselt and we look forward to seeing you at:Surface and Bulk Defects in CVD Diamond Films, X23-25 February 2005Limburgs Universitair Centrum, Diepenbeek - Hasselt, Belgiumhttp://www.imo.luc.ac.be/SBDD2005

  2. Preface: phys. stat. sol. (a) 202/11

    NASA Astrophysics Data System (ADS)

    Bergonzo, Philippe; Nesládek, Milo

    2005-09-01

    The present issue of physica status solidi (a) contains a collection of 31 papers presented at the 10th International Workshop on Surface and Bulk Defects in CVD Diamond Films held in Diepenbeek-Hasselt, Belgium, 23-25 February 2005. The 10th anniversary of the meeting proved the success of the concept, which originated in 1996 with the idea of bringing together scientists who are active and innovative in the field of electronic and optical properties of thin film diamond. This year the programme contained 9 invited oral talks, 14 contributed oral talks and 34 posters. 103 Participants from 14 countries (Austria, Belgium, Czech Republic, Finland, France, Germany, Japan, Mexico, Poland, Slovak Republic, Sweden, Switzerland, UK, USA) took part in the meeting. The meeting was traditionally directed towards topics ranging from defects and their characterization as well as electrical transport in CVD diamond towards modern diamond thin film devices including bio-sensing applications. Also, diamond homoepitaxial and heteroepitaxial growth, doping, hydrogen induced surface conductivity and several other topics including defects in boron nitride materials were addressed. Intense and lively discussions were as usual part of this meeting to which the hospitality of the city of Hasselt contributed greatly.The workshop would have not been possible without the support of many people and institutions. We also acknowledge the financial support of the Scientific Research Community of the F.W.O.-Vlaanderen (Belgium) and the University of Hasselt. We also thank the editorial staff of physica status solidi, most notably Stefan Hildebrandt, for their excellent and patient work. Finally, we would like to thank Ken Haenen, whose skills for the successful organization are gratefully acknowledged.August 2005

  3. Preface: phys. stat. sol. (b) 243/5

    NASA Astrophysics Data System (ADS)

    Artacho, Emilio; Beck, Thomas L.; Hernández, Eduardo

    Between 20 and 24 June 2005 the Centre Européen de Calcul Atomique et Moléculaire - or CECAM, as it is more widely known - hosted a workshop entitled State-of-the-art, developments and perspectives of real-space electronic structure methods in condensed-matter and chemical physics, organized with the support of CECAM itself and the ?k network. The workshop was attended by some forty participants coming from fifteen countries, and about thirty presentations were given. The workshop provided a lively forum for the discussion of recent methodological developments in electronic structure calculations, ranging from linear-scaling methods, mesh techniques, time-dependent density functional methods, and a long etcetera, which had been our ultimate objective when undertaking its organization.The first-principles simulation of solids, liquids and complex matter in general has jumped in the last few years from the relatively confined niches in condensed matter and materials physics and in quantum chemistry, to cover most of the sciences, including nano, bio, geo, environmental sciences and engineering. This effect has been propitiated by the ability of simulation techniques to deal with an ever larger degree of complexity. Although this is partially to be attributed to the steady increase in computer power, the main factor behind this change has been the coming of age of the main theoretical framework for most of the simulations performed today, together with an extremely active development of the basic algorithms for its computer implementation. It is this latter aspect that is the topic of this special issue of physica status solidi.There is a relentless effort in the scientific community seeking to achieve not only higher accuracy, but also more efficient, cost-effective and if possible simpler computational methods in electronic structure calculations [1]. From the early 1990s onwards there has been a keen interest in the computational condensed matter and chemical physics communities in methods that had the potential to overcome the unfavourable scaling of the computational cost with the system size, implicit in the momentum-space formalism familiar to solid-state physicists and the quantum chemistry approaches more common in chemical physics and physical chemistry. This interest was sparkled by the famous paper in which Weitao Yang [2] introduced the Divide and Conquer method. Soon afterwards several practical schemes aiming to achieve linear-scaling calculations, by exploiting what Walter Kohn called most aptly the near-sightedness of quantum mechanics [3], were proposed and explored (for a review on linear-scaling methods, see [4]). This search for novel, more efficient and better scaling algorithms proved to be fruitful in more than one way. Not only was it the start of several packages which are well-known today (such as Siesta, Conquest, etc.), but it also leads to new ways of representing electronic states and orbitals, such as grids [5, 6], wavelets [7], finite elements, etc. Also, the drive to exploit near-sightedness attracted computational solid state physicists to the type of atomic-like basis functions traditionally used in the quantum chemistry community. At the same time computational chemists learnt about plane waves and density functional theory, and thus a fruitful dialogue was started between two communities that hitherto had not had much contact.Another interesting development that has begun to take place over the last decade or so is the convergence of several branches of science, notably physics, chemistry and biology, at the nanoscale. Experimentalists in all these different fields are now performing highly sophisticated measurements on systems of nanometer size, the kind of systems that us theoreticians can address with our computational methods, and this convergence of experiment and theory at this scale has also been very fruitful, particularly in the fields of electronic transport and STM image simulation. It is now quite common to find papers at the cutting edge of nanoscience and nanotechnology co-authored by experimentalists and theorists, and it can only be expected that this fruitful interplay between theory and experiment will increase in the future.It was considerations such as these that moved us to propose to CECAM and ?k the celebration of a workshop devoted to the discussion of recent developments in electronic structure techniques, a proposal that was enthusiastically received, not just by CECAM and ?k, but also by our invited speakers and participants. Interest in novel electronic structure methods is now as high as ever, and we are therefore very happy that physica status solidi has given us the opportunity to devote a special issue to the topics covered in the workshop. This special issue of physica status solidi gathers invited contributions from several attendants to the workshop, contributions that are representative of the range of topics and issues discussed then, including progress in linear scaling methods, electronic transport, simulation of STM images, time-dependent DFT methods, etc. It rests for us to thank all the contributors to this special issue for their efforts, CECAM and ?k for funding the workshop, physica status solidi for agreeing to devote this special issue to the workshop, and last but not least Emmanuelle and Emilie, the CECAM secretaries, for their invaluable practical help in putting this workshop together

  4. The Phys4Entry database

    NASA Astrophysics Data System (ADS)

    Laricchiuta, Annarita

    2012-10-01

    The Phys4Entry DB is a database of state-selected dynamical information for elementary processes relevant to the state-to-state kinetic modeling of planetary-atmosphere entry conditions. The DB is intended to the challenging goal of complementing the information in the existing web-access databases, collecting and validating data of collisional dynamics of elementary processes involving ground and excited chemical species, with resolution on the electronic, vibrational and rotational degrees of freedom. Four relevant classes of elementary processes are considered, i.e. electron-molecule collisions, atom/molecule-molecule collisions, atom/molecule surface interaction and photon-induced processes, constructing a taxonomy for process classification. Data populating the DB are largely originated by the coordinated research activity done in the frame of the Phys4Entry FP7 project, considering different theoretical approaches from quantum to semi-classical or quasi-classical molecular dynamics. Nevertheless the results, obtained in the Bari plasma chemistry labs in years of research devoted to the construction of reliable state-to-state kinetic models for hydrogen and air plasmas, are also transferred to the DB. Two DB interfaces have been created for different roles allowed to different actions: the contributor, uploading new processes, and the inquirer, submitting queries, to access the complete information about the records, through a graphical tool, displaying energy or roto-vibrational dependence of dynamical data, or through the export action to download ascii datafiles. The DB is expected to have a significant impact on the modeling community working also in scientific fields different from the aerothermodynamics (i.e. fusion, environment, ), making practicable the state-to-state approach.

  5. STAT1 and STAT3 in tumorigenesis

    PubMed Central

    Avalle, Lidia; Pensa, Sara; Regis, Gabriella; Novelli, Francesco; Poli, Valeria

    2012-01-01

    The transcription factors STAT1 and STAT3 appear to play opposite roles in tumorigenesis. While STAT3 promotes cell survival/proliferation, motility and immune tolerance and is considered as an oncogene, STAT1 mostly triggers anti-proliferative and pro-apoptotic responses while enhancing anti-tumor immunity. Despite being activated downstream of common cytokine and growth factor receptors, their activation is reciprocally regulated and perturbation in their balanced expression or phosphorylation levels may re-direct cytokine/growth factor signals from proliferative to apoptotic, or from inflammatory to anti-inflammatory. Here we review the functional canonical and non-canonical effects of STAT1 and STAT3 activation in tumorigenesis and their potential cross-regulation mechanisms. PMID:24058752

  6. Summary of PhysPAG Activities

    NASA Astrophysics Data System (ADS)

    Ritz, Steven M.

    2013-01-01

    The Physics of the Cosmos (PCOS) Program Analysis Group (PhysPAG) provides an important interface between the scientific community and NASA in matters related to PCOS objectives, and also provides opportunities for community discussions. An Executive Committee facilitates the work of several subgroups, including an Inflation Probe Science Analysis Group (IPSAG), an X-ray group (XRSAG) , a gamma-ray,group (GRSAG), a gravitational wave group (GWSAG), and a cosmic-ray group (CRSAG). In addition to identifying opportunities and issues, these groups also help articulate technology needs. Membership in all the SAGs is completely open, with information and newsletter signups available on the PhysPAG pages at the PCOS program website. The PhysPAG reports to the Astrophysics Subcommittee of the NASA Advisory Council. A summary of PhysPAG activities will be given, along with time for questions and discussion.

  7. Summary of PhysPAG Activity

    NASA Astrophysics Data System (ADS)

    Nousek, John A.

    2014-01-01

    The Physics of the Cosmos Program Analysis Group (PhysPAG) is responsible for solicitiing and coordinating community input for the development and execution of NASA's Physics of the Cosmos (PCOS) program. In this session I will report on the activity of the PhysPAG, and solicit community involvement in the process of defining PCOS objectives, planning SMD architecture, and prioritizing PCOS activities. I will also report on the activities of the PhysPAG Executive Committee, which include the chairs of the Science Analysis Groups/ Science Interest Groups which fall under the PhysPAG sphere of interest. Time at the end of the presentation willl be reserved for questions and discussion from the community.

  8. Stats About Paralysis

    MedlinePlus

    ... Living with Paralysis > Stats about paralysis Stats about paralysis ☷ ▾ Page contents Prevalence of paralysis in the United ... is this research important? What’s next? Prevalence of paralysis in the United States In 2013, the Christopher & ...

  9. STAT5 acetylation

    PubMed Central

    Kosan, Christian; Ginter, Torsten; Heinzel, Thorsten; Krämer, Oliver H

    2013-01-01

    The cytokine-inducible transcription factors signal transducer and activator of transcription 5A and 5B (STAT5A and STAT5B) are important for the proper development of multicellular eukaryotes. Disturbed signaling cascades evoking uncontrolled expression of STAT5 target genes are associated with cancer and immunological failure. Here, we summarize how STAT5 acetylation is integrated into posttranslational modification networks within cells. Moreover, we focus on how inhibitors of deacetylases and tyrosine kinases can correct leukemogenic signaling nodes involving STAT5. Such small molecules can be exploited in the fight against neoplastic diseases and immunological disorders. PMID:24416653

  10. Acanthamoeba castellanii STAT Protein

    PubMed Central

    Kicinska, Anna; Leluk, Jacek; Jarmuszkiewicz, Wieslawa

    2014-01-01

    STAT (signal transducers and activators of transcription) proteins are one of the important mediators of phosphotyrosine-regulated signaling in metazoan cells. We described the presence of STAT protein in a unicellular, free-living amoebae with a simple life cycle, Acanthamoeba castellanii. A. castellanii is the only, studied to date, Amoebozoan that does not belong to Mycetozoa but possesses STATs. A sequence of the A. castellanii STAT protein includes domains similar to those of the Dictyostelium STAT proteins: a coiled coil (characteristic for Dictyostelium STAT coiled coil), a STAT DNA-binding domain and a Src-homology domain. The search for protein sequences homologous to A. castellanii STAT revealed 17 additional sequences from lower eukaryotes. Interestingly, all of these sequences come from Amoebozoa organisms that belong to either Mycetozoa (slime molds) or Centramoebida. We showed that there are four separated clades within the slime mold STAT proteins. The A. castellanii STAT protein branches next to a group of STATc proteins from Mycetozoa. We also demonstrate that Amoebozoa form a distinct monophyletic lineage within the STAT protein world that is well separated from the other groups. PMID:25338074

  11. Summary of PhysPAG Activities

    NASA Astrophysics Data System (ADS)

    Ritz, Steven M.

    2012-01-01

    The Physics of the Cosmos (PCOS) Program Analysis Group (PhysPAG) provides an important interface between the scientific community and NASA in matters related to PCOS objectives. An Executive Committee facilitates the work of several subgroups, including a Technology Science Analysis Group and an Inflation Probe Science Analysis Group. Work is also starting in areas of X-ray, gamma-ray, and gravitational wave astrophysics. The PAG reports to the Astrophysics Subcommittee of the NASA Advisory Council. A summary of PhysPAG activities will be given, along with time for questions and discussion.

  12. Expanding the PhysTEC Coalition

    NASA Astrophysics Data System (ADS)

    Stein, Fredrick

    2003-04-01

    The Physics Teacher Education Coalition (PhysTEC) is a community of physics departments representing scientists and educators at institutions dedicated to improving the science preparation of future K-12 teachers. Now in its second year, PhysTEC requires physics and education faculty to work together to provide an education for future teachers that emphasizes interactive engagement and a student-centered approach to learning science. The first six Coalition members are the physics departments at Ball State University, Oregon State University, University of Arizona, University of Arkansas, Western Michigan University, and Xavier University of Louisiana. PhysTEC is creating a broad, active Coalition of physics departments that have implemented or are interested in implementing one or more of the PhysTEC Program Components. · A long-term, active collaboration among the physics department, the department of education, and the local schools. · A Teacher-in-Residence (TIR) program that provides for a full-time participant in assisting faculty in course revisions. · The redesign of physics courses based on results from physics education research. · The redesign of elementary and secondary science methods courses with an emphasis on inquiry-based teaching and learning. · The establishment of a mentoring program to provide a valuable induction experience for novice science teachers. · The participation of physics faculty in the improvement and expansion of school experiences. www.phystec.org

  13. STAT inhibitors for cancer therapy

    PubMed Central

    2013-01-01

    Signal Transducer and Activator of Transcription (STAT) proteins are a family of cytoplasmic transcription factors consisting of 7 members, STAT1 to STAT6, including STAT5a and STAT5b. STAT proteins are thought to be ideal targets for anti-cancer therapy since cancer cells are more dependent on the STAT activity than their normal counterparts. Inhibitors targeting STAT3 and STAT5 have been developed. These included peptidomimetics, small molecule inhibitors and oligonucleotides. This review summarized advances in preclinical and clinical development of these compounds. PMID:24308725

  14. PeriStats: Perinatal Statistics

    MedlinePlus

    ... can narrow your results by year or health indicator or compare with another region. To get the ... the data on PeriStats? How are the health indicators on PeriStats calculated? Is it possible to suggest ...

  15. Montana StreamStats

    USGS Publications Warehouse

    2016-04-05

    About this volumeMontana StreamStats is a Web-based geographic information system (http://water.usgs.gov/osw/streamstats/) application that provides users with access to basin and streamflow characteristics for gaged and ungaged streams in Montana. Montana StreamStats was developed by the U.S. Geological Survey (USGS) in cooperation with the Montana Departments of Transportation, Environmental Quality, and Natural Resources and Conservation. The USGS Scientific Investigations Report consists of seven independent but complementary chapters dealing with various aspects of this effort.Chapter A describes the Montana StreamStats application, the basin and streamflow datasets, and provides a brief overview of the streamflow characteristics and regression equations used in the study. Chapters B through E document the datasets, methods, and results of analyses to determine streamflow characteristics, such as peak-flow frequencies, low-flow frequencies, and monthly and annual characteristics, for USGS streamflow-gaging stations in and near Montana. The StreamStats analytical toolsets that allow users to delineate drainage basins and solve regression equations to estimate streamflow characteristics at ungaged sites in Montana are described in Chapters F and G.

  16. Fast wave power flow along SOL field lines in NSTX

    NASA Astrophysics Data System (ADS)

    Perkins, R. J.; Bell, R. E.; Diallo, A.; Gerhardt, S.; Hosea, J. C.; Jaworski, M. A.; Leblanc, B. P.; Kramer, G. J.; Phillips, C. K.; Roquemore, L.; Taylor, G.; Wilson, J. R.; Ahn, J.-W.; Gray, T. K.; Green, D. L.; McLean, A.; Maingi, R.; Ryan, P. M.; Jaeger, E. F.; Sabbagh, S.

    2012-10-01

    On NSTX, a major loss of high-harmonic fast wave (HHFW) power can occur along open field lines passing in front of the antenna over the width of the scrape-off layer (SOL). Up to 60% of the RF power can be lost and at least partially deposited in bright spirals on the divertor floor and ceiling [1,2]. The flow of HHFW power from the antenna region to the divertor is mostly aligned along the SOL magnetic field [3], which explains the pattern of heat deposition as measured with infrared (IR) cameras. By tracing field lines from the divertor back to the midplane, the IR data can be used to estimate the profile of HHFW power coupled to SOL field lines. We hypothesize that surface waves are being excited in the SOL, and these results should benchmark advanced simulations of the RF power deposition in the SOL (e.g., [4]). Minimizing this loss is critical optimal high-power long-pulse ICRF heating on ITER while guarding against excessive divertor erosion.[4pt] [1] J.C. Hosea et al., AIP Conf Proceedings 1187 (2009) 105. [0pt] [2] G. Taylor et al., Phys. Plasmas 17 (2010) 056114. [0pt] [3] R.J. Perkins et al., to appear in Phys. Rev. Lett. [0pt] [4] D.L. Green et al., Phys. Rev. Lett. 107 (2011) 145001.

  17. FastStats: Contraceptive Use

    MedlinePlus

    ... Inflicted Injury Life Stages and Populations Age Groups Adolescent Health Child Health Infant Health Older Persons' Health ... Contraceptive Use Infertility Reproductive Health Notice Regarding FastStats Mobile Application Get Email Updates To receive email updates ...

  18. FastStats: Sinus Conditions

    MedlinePlus

    ... please visit this page: About CDC.gov . FastStats Homepage Diseases and Conditions Anemia or Iron Deficiency Arthritis ... Statistics Tables for U.S. Adults: National Health Interview Survey, 2014, Table A-2 [PDF - 219 KB] Physician ...

  19. STAT Overview and SCENIC Functional Concept

    NASA Technical Reports Server (NTRS)

    Welch, Bryan

    2016-01-01

    This is an overview of the guiding principles of STAT derivation from back in early 2012. This includes a functional view of STAT operations, a STAT demonstration, as well as how the STAT functional view is an excellent model, in my perspective, how the necessary functional view for the SCENIC Analysis Tool.

  20. Research-based resources on PhysPort

    NASA Astrophysics Data System (ADS)

    Sayre, Eleanor

    2017-01-01

    PhysPort (http://physport.org) is a website that supports physics faculty in implementing research-based teaching practices in their classrooms. We provide expert recommendations and practical information about teaching methods and assessment. The PhysPort Data Explorer is an intuitive online tool for physics faculty to analyze their assessment data. Faculty upload their students' responses using our secure interface. The Data Explorer matches their pre/post data, scores it, compares it to national data, and graphs it in an interactive and intuitive manner. The Periscope collection on Physport brings together classroom video of students working groups with professional development materials for faculty, pre-service teachers, and learning assistants. To support PhysPort's development efforts, we conduct research on faculty needs around teaching and assessment, secondary analysis of published PER studies, and primary analysis of assessment data. In this talk, I'll introduce some of PhysPort's research-based resources and the research results which support them.

  1. STAT5-Interacting Proteins: A Synopsis of Proteins that Regulate STAT5 Activity

    PubMed Central

    Able, Ashley A.; Burrell, Jasmine A.; Stephens, Jacqueline M.

    2017-01-01

    Signal Transducers and Activators of Transcription (STATs) are key components of the JAK/STAT pathway. Of the seven STATs, STAT5A and STAT5B are of particular interest for their critical roles in cellular differentiation, adipogenesis, oncogenesis, and immune function. The interactions of STAT5A and STAT5B with cytokine/hormone receptors, nuclear receptors, transcriptional regulators, proto-oncogenes, kinases, and phosphatases all contribute to modulating STAT5 activity. Among these STAT5 interacting proteins, some serve as coactivators or corepressors to regulate STAT5 transcriptional activity and some proteins can interact with STAT5 to enhance or repress STAT5 signaling. In addition, a few STAT5 interacting proteins have been identified as positive regulators of STAT5 that alter serine and tyrosine phosphorylation of STAT5 while other proteins have been identified as negative regulators of STAT5 via dephosphorylation. This review article will discuss how STAT5 activity is modulated by proteins that physically interact with STAT5. PMID:28287479

  2. Function of shrimp STAT during WSSV infection.

    PubMed

    Wen, Rong; Li, Fuhua; Li, Shihao; Xiang, Jianhai

    2014-06-01

    JAK/STAT signaling pathway plays key roles in the antiviral immunity of mammals, fish and insect. However, limited knowledge is known about the function of JAK/STAT signaling pathway in the antiviral immunity of shrimp although virus disease has caused severe mortality in shrimp aquaculture. In order to understand the function of JAK/STAT signaling pathway in the antiviral immunity of shrimp, dsRNA interfering technique was used to silence the expression of STAT gene in Litopenaeus vannamei, and the mortality of shrimp was detected after WSSV infection. Furthermore, the expressions of some potential target genes regulated by STAT or genes related to RNA interfering pathway were detected in STAT silenced shrimp during WSSV infection. The WSSV copy number in STAT silenced shrimp was 10(2)-10(3) copies/ng DNA which was much lower than that in the control. The mortality in STAT silenced shrimp caused by WSSV infection decreased very significantly compared to their controls. The function of STAT was verified in vitro cultured cells of hematopoietic tissue of crayfish Cherax quadricarinatus by adding specific inhibitor of STAT3(S3I-201), and the cultured cells treated with S3I-201 showed much less WSSV copy number than their controls, which further suggested that STAT might be helpful for the replication of WSSV. Expression analysis on the potential STAT target genes and genes in RNA interfering pathway provide important information for understanding the functional mechanism of STAT in antiviral immunity of shrimp.

  3. STAT6 — EDRN Public Portal

    Cancer.gov

    STAT6 is a member of the STAT family of transcription factors. STAT family members are phosphorylated by the receptor associated kinases in response to cytokines and growth factors and are involved in signal transduction and activation of transcription. There are several transcript variants produced by alternative splicing.

  4. A Sequence of the CIS Gene Promoter Interacts Preferentially with Two Associated STAT5A Dimers: a Distinct Biochemical Difference between STAT5A and STAT5B

    PubMed Central

    Verdier, Frédérique; Rabionet, Raquel; Gouilleux, Fabrice; Beisenherz-Huss, Christian; Varlet, Paule; Muller, Odile; Mayeux, Patrick; Lacombe, Catherine; Gisselbrecht, Sylvie; Chretien, Stany

    1998-01-01

    Two distinct genes encode the closely related signal transducer and activator of transcription proteins STAT5A and STAT5B. The molecular mechanisms of gene regulation by STAT5 and, particularly, the requirement for both STAT5 isoforms are still undetermined. Only a few STAT5 target genes, among them the CIS (cytokine-inducible SH2-containing protein) gene, have been identified. We cloned the human CIS gene and studied the human CIS gene promoter. This promoter contains four STAT binding elements organized in two pairs. By electrophoretic mobility shift assay studies using nuclear extracts of UT7 cells stimulated with erythropoietin, we showed that these four sequences bound to STAT5-containing complexes that exhibited different patterns and affinities: the three upstream STAT binding sequences bound to two distinct STAT5-containing complexes (C0 and C1) and the downstream STAT box bound only to the slower-migrating C1 band. Using nuclear extracts from COS-7 cells transfected with expression vectors for the prolactin receptor, STAT5A, and/or STAT5B, we showed that the C1 complex was composed of a STAT5 tetramer and was dependent on the presence of STAT5A. STAT5B lacked this property and bound with a stronger affinity than did STAT5A to the four STAT sequences as a homodimer (C0 complex). This distinct biochemical difference between STAT5A and STAT5B was confirmed with purified activated STAT5 recombinant proteins. Moreover, we showed that the presence on the same side of the DNA helix of a second STAT sequence increased STAT5 binding and that only half of the palindromic STAT binding sequence was sufficient for the formation of a STAT5 tetramer. Again, STAT5A was essential for this cooperative tetrameric association. This property distinguishes STAT5A from STAT5B and could be essential to explain the transcriptional regulation diversity of STAT5. PMID:9742102

  5. The PhysTEC Teacher Education Program at FIU

    NASA Astrophysics Data System (ADS)

    Kramer, Laird

    2010-10-01

    The FIU PhysTEC Project is an integral component of the Physics Department's educational transformation that has led to more than a ten-fold increase in majors. The transformation seeks to increase the quality and quantity of physics majors and future physics teachers, including those from historically underrepresented groups. Elements of the efforts include transformed introductory physics courses, establishment of a physics research and learning community, engagement of stakeholders spanning high school through the university administration, and advocacy by a physics education research group. The PhysTEC Project supports future physics teachers through a Learning Assistant program coupled to newly revised secondary education programs. The Learning Assistant program is an experiential program that recruits new students into teaching careers while providing a mechanism for transforming courses - undergraduates experience the rewards and intellectual challenges of teaching through providing interactive engagement learning experiences for their peers in introductory physics courses. Students that continue in the program enroll in a multidisciplinary teacher preparation program and may receive significant financial support. FIU is a minority-serving urban public research institution in Miami, Florida serving over 39,000 students, of which 64% are Hispanic, 13% are Black, and 56% are women. Programmatic strategies and impacts of the program will be provided.

  6. STAT5 in Cancer and Immunity.

    PubMed

    Rani, Aradhana; Murphy, John J

    2016-04-01

    Signal transducers and activators of transcription 5 (STAT5a and STAT5b) are highly homologous proteins that are encoded by 2 separate genes and are activated by Janus-activated kinases (JAK) downstream of cytokine receptors. STAT5 proteins are activated by a wide variety of hematopoietic and nonhematopoietic cytokines and growth factors, all of which use the JAK-STAT signalling pathway as their main mode of signal transduction. STAT5 proteins critically regulate vital cellular functions such as proliferation, differentiation, and survival. The physiological importance of STAT5 proteins is underscored by the plethora of primary human tumors that have aberrant constitutive activation of these proteins, which significantly contributes to tumor cell survival and malignant progression of disease. STAT5 plays an important role in the maintenance of normal immune function and homeostasis, both of which are regulated by specific members of IL-2 family of cytokines, which share a common gamma chain (γ(c)) in their receptor complex. STAT5 critically mediates the biological actions of members of the γ(c) family of cytokines in the immune system. Essentially, STAT5 plays a critical role in the function and development of Tregs, and consistently activated STAT5 is associated with a suppression in antitumor immunity and an increase in proliferation, invasion, and survival of tumor cells. Thus, therapeutic targeting of STAT5 is promising in cancer.

  7. The PhysTec Project of APS, AIP, and AAPT

    NASA Astrophysics Data System (ADS)

    Jansen, Henri

    2002-04-01

    We will describe the development of the PhysTEC program at Oregon State University. The goal of this program is to enhance the number of secondary physics teachers and to improve the physics training of primary teachers and secondary teachers in related fields. Key elements of the plan include: (1) a seamless five-year program leading to a M.S. in science education and a B.S. in physics with a specialty in physics education, which takes advantage of our unique undergraduate physics curriculum (the Paradigms project); (2) a teacher-in-residence with joint duties in the Department of Physics and the Department of Science and Math Education; (3) inquiry-based and pedagogically-oriented lab and recitation sections in calculus-based introductory physics; (4) an inquiry-based physical science course for preservice elementary teachers; (5) outreach projects that enhance the preservice experience and support the methods and pedagogy training offered elsewhere in the curriculum.

  8. Antagonizing STAT5B dimerization with an osmium complex

    PubMed Central

    Liu, Li-Juan; Wang, Wanhe; Kang, Tian-Shu; Liang, Jia-Xin; Liu, Chenfu; Kwong, Daniel W. J.; Wong, Vincent Kam Wai; Ma, Dik-Lung; Leung, Chung-Hang

    2016-01-01

    Targeting STAT5 is an appealing therapeutic strategy for the treatment of hematologic malignancies and inflammation. Here, we present the novel osmium(II) complex 1 as the first metal-based inhibitor of STAT5B dimerization. Complex 1 exhibited superior inhibitory activity against STAT5B DNA binding compared to STAT5A DNA binding. Moreover, 1 repressed STAT5B transcription and blocked STAT5B dimerization via binding to the STAT5B protein, thereby inhibiting STAT5B translocation to the nucleus. Furthermore, 1 was able to selectively inhibit STAT5B phosphorylation without affecting the expression level of STAT5B. PMID:27853239

  9. Density Limit due to SOL Convection

    NASA Astrophysics Data System (ADS)

    D'Ippolito, D. A.; Myra, J. R.; Russell, D. A.

    2004-11-01

    Recent measurements on C-Mod(M. Greenwald, Plasma Phys. Contr. Fusion 44), R27 (2002). suggest there is a density limit due to rapid convection in the SOL: this region starts in the far SOL but expands inward to the separatrix as the density approaches the Greenwald limit. This idea is supported by a recent analysis(D. A. Russell et al., Lodestar Report LRC-04-99 (2004).) of a 3D BOUT code turbulence simulation(X. Q. Xu et al., Bull. APS 48), 184 (2003), paper KP1-20. with neutral fueling of the X-point region. Our work suggests that rapid outwards convection of plasma by turbulent coherent structures (``blobs'') occurs when the X-point collisionality is sufficiently large. Here, we calculate a density limit due to loss of thermal equilibrium in the edge plasma due to rapid radial convective heat transport. We expect a synergistic effect between blob convection and X-point cooling. The cooling increases the parallel resistivity at the X-point, ``disconnects'' the blobs electrically from the sheaths, and increases their radial velocity,(D.A. D'Ippolito et al., 2004 Sherwood Meeting, paper 1C 43.) which in turn further cools the X-points. Progress on a theoretical model will be reported.

  10. STAT5 Outcompetes STAT3 To Regulate the Expression of the Oncogenic Transcriptional Modulator BCL6

    PubMed Central

    Walker, Sarah R.; Nelson, Erik A.; Yeh, Jennifer E.; Pinello, Luca; Yuan, Guo-Cheng

    2013-01-01

    Inappropriate activation of the transcription factors STAT3 and STAT5 has been shown to drive cancer pathogenesis through dysregulation of genes involved in cell survival, growth, and differentiation. Although STAT3 and STAT5 are structurally related, they can have opposite effects on key genes, including BCL6. BCL6, a transcriptional repressor, has been shown to be oncogenic in diffuse large B cell lymphoma. BCL6 also plays an important role in breast cancer pathogenesis, a disease in which STAT3 and STAT5 can be activated individually or concomitantly. To determine the mechanism by which these oncogenic transcription factors regulate BCL6 transcription, we analyzed their effects at the levels of chromatin and gene expression. We found that STAT3 increases expression of BCL6 and enhances recruitment of RNA polymerase II phosphorylated at a site associated with transcriptional initiation. STAT5, in contrast, represses BCL6 expression below basal levels and decreases the association of RNA polymerase II at the gene. Furthermore, the repression mediated by STAT5 is dominant over STAT3-mediated induction. STAT5 exerts this effect by displacing STAT3 from one of the two regulatory regions to which it binds. These findings may underlie the divergent biology of breast cancers containing activated STAT3 alone or in conjunction with activated STAT5. PMID:23716595

  11. SOL Thermal Instability due to Radial Blob Convection

    NASA Astrophysics Data System (ADS)

    D'Ippolito, D. A.

    2005-10-01

    C-Mod datafootnotetextM. Greenwald, Plasma Phys. Contr. Fusion 44, R27 (2002). suggests a density limit when rapid perpendicular convection dominates SOL heat transport. This is supported by a recent analysisfootnotetextD.A. Russell et al., Phys. Rev. Lett. 93, 265001 (2004). of BOUT code turbulence simulations, which shows that rapid outwards convection of plasma by turbulent blobs is enhanced when the X-point collisionality is large, resulting in a synergistic effect between blob convection and X-point cooling. This work motivates the present analysis of SOL thermal equilibrium and instability including an RX-regime modelfootnotetextJ.R. Myra and D.A. D'Ippolito, Lodestar Report LRC-05-105 (2005). of blob particle and heat transport. Two-point (midplane, X-point) SOL thermal equilibrium and stability models are considered including both two-field (T) and four-field (n,T) treatments. The conditions under which loss of thermal equilibrium or thermal instabilities occur are established, and relations to the C-Mod data are described.

  12. PREFACE: Prospects in Neutrino Physics 2013 - NuPhys2013

    NASA Astrophysics Data System (ADS)

    2015-04-01

    The first "Prospects in Neutrino Physics 2013 - NuPhys2013" conference was held at the Institute of Physics, IoP, London, 19-20 December 2013 and was attended by about 130 delegates from institutions worldwide. Lunch and coffee breaks allowed discussions among delegates and speakers to take place in an informal setting. This conference is unique in discussing the worldwide strategy to address unresolved issues in neutrino physics, and shape the future directions of particle physics. We discussed the current status and focussed especially on the prospects of future experiments, their performance and physics reach. It is particularly timely due to the recent measurements in neutrino physics and planned worldwide experiments. The following topics were addressed: • Theory and Phenomenology Perspectives • Future Long and Short Baseline Neutrino Oscillation Experiments • Reactor neutrino and flux • Neutrinoless double beta decays • Solar, atmospheric, supernova neutrinos • Neutrino cosmology in which both the phenomenological and experimental aspects were equally addressed. World-leading experts in the different neutrino areas were invited to give review talks. To encourage and facilitate the participation of early-career researchers and PhD students, a poster session formed a key aspect of this meeting. The conference was organized by Francesca Di Lodovico and Silvia Pascoli. It was sponsored by the IoP through their Topic Research Meeting Grant, and also supported by Durham IPPP, ERC-207282, FP7 invisibles project, Queen Mary University of London.

  13. Sol-gel coatings for high pressure polarized ^3He nuclear targets

    NASA Astrophysics Data System (ADS)

    Deur, Alexandre; Cates, Gordon D.; Chaput, Julien; Singh, Jaideep; Tobias, William A.

    2001-11-01

    Sol-gel coated glass cells have been shown to exhibit longitudinal lifetimes T1 in excess of 350 hours for ^3He that is polarized by spin-exchange optical pumping.( Ming F. Hsu shape et al, Appl. Phys. Lett.) series 77 (2000) 2069. The sol-gel technique was designed to minimize spin-relaxation due to wall collisions so that only dipole-dipole interactions between colliding ^3He atoms dominate in the relaxation process. Until now, sol-gel technology has not been applied to high pressure ^3He gas targets used in nuclear scattering experiments. Latest developments on incorporating the sol-gel technique in the production of these ^3He targets will be presented.

  14. Screening approaches to generating STAT inhibitors

    PubMed Central

    Walker, Sarah R.; Frank, David A.

    2012-01-01

    STAT transcription factors are regulators of critical cellular processes such as proliferation, survival, and self-renewal. While the activity of these proteins is tightly regulated under physiological conditions, they can become constitutively activated in a broad range of human cancers. This inappropriate STAT activation leads to enhanced transcription of genes that can directly lead to the malignant phenotype. Since STATs are largely dispensable for normal cell function, this has raised the possibility that STATs might be key targets for cancer therapy. Although a number of structure-based strategies have been used to develop STAT inhibitors, an alternate approach is to use cell-based assays that make use of the transcriptional function of STATs. Employing these systems, one can screen large chemical libraries to identify compounds that specifically block the function of a given STAT. This approach can lead to the identification of compounds that inhibit STATs by a variety of mechanisms, and can suggest novel targets for therapy. This type of functional screening strategy has already identified a drug that potently inhibits STAT3, and which is now being evaluated in a clinical trial for patients with chronic lymphocytic leukemia. PMID:24058786

  15. Acetylation modulates the STAT signaling code.

    PubMed

    Wieczorek, Martin; Ginter, Torsten; Brand, Peter; Heinzel, Thorsten; Krämer, Oliver H

    2012-12-01

    A fascinating question of modern biology is how a limited number of signaling pathways generate biological diversity and crosstalk phenomena in vivo. Well-defined posttranslational modification patterns dictate the functions and interactions of proteins. The signal transducers and activators of transcription (STATs) are physiologically important cytokine-induced transcription factors. They are targeted by a multitude of posttranslational modifications that control and modulate signaling responses and gene expression. Beyond phosphorylation of serine and tyrosine residues, lysine acetylation has recently emerged as a critical modification regulating STAT functions. Interestingly, acetylation can determine STAT signaling codes by various molecular mechanisms, including the modulation of other posttranslational modifications. Here, we provide an overview on the acetylation of STATs and how this protein modification shapes cellular cytokine responses. We summarize recent advances in understanding the impact of STAT acetylation on cell growth, apoptosis, innate immunity, inflammation, and tumorigenesis. Furthermore, we discuss how STAT acetylation can be targeted by small molecules and we consider the possibility that additional molecules controlling STAT signaling are regulated by acetylation. Our review also summarizes evolutionary aspects and we show similarities between the acetylation-dependent control of STATs and other important molecules. We propose the concept that, similar to the 'histone code', distinct posttranslational modifications and their crosstalk orchestrate the functions and interactions of STAT proteins.

  16. Telltale Animation (Sol 9)

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This animation of the NASA's Phoenix Mars Lander's telltale was made from five images taken by Phoenix's Stereo Surface Imager (SSI) just after 4:37 PM local Mars time on the ninth Martian day of the mission, or Sol 9 (June 3, 2008). The images were taken with a blue filter (450 nanometer, R6) that focuses at items on the deck rather than the workspace or horizon.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  17. Telltale Animation (Sol 9)

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This animation of the NASA's Phoenix Mars Lander's telltale was made from five images taken by Phoenix's Stereo Surface Imager (SSI) near 3:00 PM local Mars time on the ninth Martian day of the mission, or Sol 9 (June 3, 2008). The images were taken with a blue filter (450 nanometer, R6) that focuses at items on the deck rather than the workspace or horizon.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  18. Telltale Animation (Sol 8)

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This animation of the NASA's Phoenix Mars Lander's telltale was made from five images taken by Phoenix's Stereo Surface Imager (SSI) just after 1:10 PM local Mars time on the eighth Martian day of the mission, or Sol 8 (June 2, 2008). The images were taken with a blue filter (450 nanometer, R6) that focuses at items on the deck rather than the workspace or horizon.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  19. Rapid change of blob structure in the outer scrape-off layer (SOL)

    NASA Astrophysics Data System (ADS)

    Cohen, R. H.

    2005-10-01

    Nonlinear structures (``blobs'') driven by the magnetic field curvature and highly elongated along the field lines may exist in the tokamak SOL.footnotetextS.I. Krasheninnikov. Phys. Lett. A 283, 368 (2001) The contact of the blob end with the divertor plate significantly affects the blob structure and velocity. However, the strong shearing of the flux-tube near the X-point makes impossible direct electrical contact of the blob in the upper SOL and the divertor, so that the sheath boundary condition (BC) has to be replaced by a BC imposed near the X point.footnotetextD. Ryutov, R.H. Cohen. Contr. Pl. Phys 44, 168 (2004) We show that, at larger distances from the separatrix, in the far SOL, the connection between the upper SOL and the divertor plate is re-established, and the sheath BC becomes again relevant. During the blob's outward radial motion, this event is reflected in a sudden change of its length, from the blob extending only to the X point to the blob extending down to the plate. Likewise, a blob initially existing only in the divertor leg becomes suddenly longer, and extends to the whole SOL.

  20. Nanocrystal/sol-gel nanocomposites

    DOEpatents

    Petruska, Melissa A.; Klimov, Victor L.

    2007-06-05

    The present invention is directed to solid composites including colloidal nanocrystals within a sol-gel host or matrix and to processes of forming such solid composites. The present invention is further directed to alcohol soluble colloidal nanocrystals useful in formation of sol-gel based solid composites.

  1. Nanocrystal/sol-gel nanocomposites

    SciTech Connect

    Petruska, Melissa A; Klimov, Victor L

    2012-06-12

    The present invention is directed to solid composites including colloidal nanocrystals within a sol-gel host or matrix and to processes of forming such solid composites. The present invention is further directed to alcohol soluble colloidal nanocrystals useful in formation of sol-gel based solid composites

  2. STATs in cancer inflammation and immunity: a leading role for STAT3.

    PubMed

    Yu, Hua; Pardoll, Drew; Jove, Richard

    2009-11-01

    Commensurate with their roles in regulating cytokine-dependent inflammation and immunity, signal transducer and activator of transcription (STAT) proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer. Persistently activated STAT3 and, to some extent, STAT5 increase tumour cell proliferation, survival and invasion while suppressing anti-tumour immunity. The persistent activation of STAT3 also mediates tumour-promoting inflammation. STAT3 has this dual role in tumour inflammation and immunity by promoting pro-oncogenic inflammatory pathways, including nuclear factor-kappaB (NF-kappaB) and interleukin-6 (IL-6)-GP130-Janus kinase (JAK) pathways, and by opposing STAT1- and NF-kappaB-mediated T helper 1 anti-tumour immune responses. Consequently, STAT3 is a promising target to redirect inflammation for cancer therapy.

  3. STATs in cancer inflammation and immunity: a leading role for STAT3

    PubMed Central

    Yu, Hua; Pardoll, Drew; Jove, Richard

    2016-01-01

    Commensurate with their roles in regulating cytokine-dependent inflammation and immunity, signal transducer and activator of transcription (STAT) proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer. Persistently activated STAT3 and, to some extent, STAT5 increase tumour cell proliferation, survival and invasion while suppressing anti-tumour immunity. The persistent activation of STAT3 also mediates tumour-promoting inflammation. STAT3 has this dual role in tumour inflammation and immunity by promoting pro-oncogenic inflammatory pathways, including nuclear factor-κB (NF-κB) and interleukin-6 (IL-6)–GP130–Janus kinase (JAK) pathways, and by opposing STAT1- and NF-κB-mediated T helper 1 anti-tumour immune responses. Consequently, STAT3 is a promising target to redirect inflammation for cancer therapy. PMID:19851315

  4. STAT signaling in the pathogenesis and treatment of myeloid malignancies

    PubMed Central

    Bar-Natan, Michal; Nelson, Erik A.; Xiang, Michael; Frank, David A.

    2012-01-01

    STAT transcription factors play a critical role in mediating the effects of cytokines on myeloid cells. As STAT target genes control key processes such as survival, proliferation and self-renewal, it is not surprising that constitutive activation of STATs, particularly STAT3 and STAT5, are common events in many myeloid tumors. STATs are activated both by mutant tyrosine kinases as well as other pathogenic events, and continued activation of STATs is common in the setting of resistance to kinase inhibitors. Thus, the targeting of STATs, alone or in combination with other drugs, will likely have increasing importance for cancer therapy. PMID:24058751

  5. The role of STAT3 in autophagy.

    PubMed

    You, Liangkun; Wang, Zhanggui; Li, Hongsen; Shou, Jiawei; Jing, Zhao; Xie, Jiansheng; Sui, Xinbing; Pan, Hongming; Han, Weidong

    2015-01-01

    Autophagy is an evolutionarily conserved process in eukaryotes that eliminates harmful components and maintains cellular homeostasis in response to a series of extracellular insults. However, these insults may trigger the downstream signaling of another prominent stress responsive pathway, the STAT3 signaling pathway, which has been implicated in multiple aspects of the autophagic process. Recent reports further indicate that different subcellular localization patterns of STAT3 affect autophagy in various ways. For example, nuclear STAT3 fine-tunes autophagy via the transcriptional regulation of several autophagy-related genes such as BCL2 family members, BECN1, PIK3C3, CTSB, CTSL, PIK3R1, HIF1A, BNIP3, and microRNAs with targets of autophagy modulators. Cytoplasmic STAT3 constitutively inhibits autophagy by sequestering EIF2AK2 as well as by interacting with other autophagy-related signaling molecules such as FOXO1 and FOXO3. Additionally, the mitochondrial translocation of STAT3 suppresses autophagy induced by oxidative stress and may effectively preserve mitochondria from being degraded by mitophagy. Understanding the role of STAT3 signaling in the regulation of autophagy may provide insight into the classic autophagy model and also into cancer therapy, especially for the emerging targeted therapy, because a series of targeted agents execute antitumor activities via blocking STAT3 signaling, which inevitably affects the autophagy pathway. Here, we review several of the representative studies and the current understanding in this particular field.

  6. Spirit Traverse Map, Sol 680

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Annotated Spirit Traverse Map

    This image shows the route that NASA's Mars Exploration Rover Spirit has driven inside Gusev Crater from its first Martian day (sol 1) to its 680th sol (Dec. 1, 2005), more than a complete Martian year. The underlying image (previously released as PIA07849) is a mosaic of images from the Mars Orbiter Camera on NASA's Mars Global Surveyor orbiter. The scale bar at lower left is 500 meters (0.31 mile). As of sol 680, Spirit had driven a total of 5,495 meters (3.41 miles).

  7. Physics of the Cosmos Program Analysis Group (PhysPAG) Report

    NASA Astrophysics Data System (ADS)

    Nousek, John A.

    2015-01-01

    The Physics of the Cosmos Program Analysis Group (PhysPAG) serves as a forum for soliciting and coordinating input and analysis from the scientific community in support of the PCOS program objectives. I will outline the activities of the PhysPAG over the past year, since the last meeting during the AAS meeting in National Harbor, and mention the activities of the PhysPAG related Scientific Interest Groups.

  8. STAT1 and STAT3 in tumorigenesis: A matter of balance.

    PubMed

    Avalle, Lidia; Pensa, Sara; Regis, Gabriella; Novelli, Francesco; Poli, Valeria

    2012-04-01

    The transcription factors STAT1 and STAT3 appear to play opposite roles in tumorigenesis. While STAT3 promotes cell survival/proliferation, motility and immune tolerance and is considered as an oncogene, STAT1 mostly triggers anti-proliferative and pro-apoptotic responses while enhancing anti-tumor immunity. Despite being activated downstream of common cytokine and growth factor receptors, their activation is reciprocally regulated and perturbation in their balanced expression or phosphorylation levels may re-direct cytokine/growth factor signals from proliferative to apoptotic, or from inflammatory to anti-inflammatory. Here we review the functional canonical and non-canonical effects of STAT1 and STAT3 activation in tumorigenesis and their potential cross-regulation mechanisms.

  9. Employing Introductory Statistics Students at "Stats Dairy"

    ERIC Educational Resources Information Center

    Keeling, Kellie

    2011-01-01

    To combat students' fear of statistics I employ my students at a fictional company, Stats Dairy, run by cows. Almost all examples used in the class notes, exercises, humour and exams use data "collected" from this company.

  10. FastStats: Older Persons' Health

    MedlinePlus

    ... 11 [PDF - 4.4 MB] Leading causes of death of persons age 65 and over Heart disease ... More data Adult Day Services Centers AgingStats.gov Deaths From Unintentional Injury Among Adults Aged 65 and ...

  11. The JAK-STAT Pathway at Twenty

    PubMed Central

    Stark, George R.; Darnell, James E.

    2014-01-01

    We look back on the discoveries that the tyrosine kinases TYK2 and JAK1 and the transcription factors STAT1, STAT2, and IRF9 are required for the cellular response to type I interferons. This initial description of the JAK-STAT pathway led quickly to additional discoveries that type II interferons and many other cytokines signal through similar mechanisms. This well-understood pathway now serves as a paradigm showing how information from protein-protein contacts at the cell surface can be conveyed directly to genes in the nucleus. We also review recent work on the STAT proteins showing the importance of several different posttranslational modifications, including serine phosphorylation, acetylation, methylation, and sumoylation. These remarkably proficient proteins also provide noncanonical functions in transcriptional regulation and they also function in mitochondrial respiration and chromatin organization in ways that may not involve transcription at all. PMID:22520844

  12. Alternative Splicing of STAT3 Is Affected by RNA Editing.

    PubMed

    Goldberg, Lior; Abutbul-Amitai, Mor; Paret, Gideon; Nevo-Caspi, Yael

    2017-03-09

    A-to-I RNA editing, carried out by adenosine deaminase acting on RNA (ADAR) enzymes, is an epigenetic phenomenon of posttranscriptional modifications on pre-mRNA. RNA editing in intronic sequences may influence alternative splicing of flanking exons. We have previously shown that conditions that induce editing result in elevated expression of signal transducer and activator of transcription 3 (STAT3), preferentially the alternatively-spliced STAT3β isoform. Mechanisms regulating alternative splicing of STAT3 have not been elucidated. STAT3 undergoes A-to-I RNA editing in an intron residing in proximity to the alternatively spliced exon. We hypothesized that RNA editing plays a role in regulating alternative splicing toward STAT3β. In this study we extend our observation connecting RNA editing to the preferential induction of STAT3β expression. We study the involvement of ADAR1 in STAT3 editing and reveal the connection between editing and alternative splicing of STAT3. Deferoaxamine treatment caused the induction in STAT3 RNA editing and STAT3β expression. Silencing ADAR1 caused a decrease in STAT3 editing and expression with a preferential decrease in STAT3β. Cells transfected with a mutated minigene showed preferential splicing toward the STAT3β transcript. Editing in the STAT3 intron is performed by ADAR1 and affects STAT3 alternative splicing. These results suggest that RNA editing is one of the molecular mechanisms regulating the expression of STAT3β.

  13. Distinct roles of STAT3 and STAT5 in the pathogenesis and targeted therapy of breast cancer

    PubMed Central

    Walker, Sarah R.; Xiang, Michael; Frank, David A.

    2013-01-01

    The transcription factors STAT3 and STAT5 play important roles in the regulation of mammary gland function during pregnancy, lactation, and involution. Given that STAT3 and STAT5 regulate genes involved in proliferation and survival, it is not surprising that inappropriate activation of STAT3 and STAT5 occurs commonly in breast cancer. Although these proteins are structurally similar, they have divergent and opposing effects on gene expression and cellular phenotype. Notably, when STAT5 and STAT3 are activated simultaneously, STAT5 has a dominant effect, and leads to decreased proliferation and increased sensitivity to cell death. Similarly, in breast cancer, activation of both STAT5 and STAT3 is associated with longer patient survival than activation of STAT3 alone. Pharmacological inhibitors of STAT3 and STAT5 are being developed for cancer therapy, though understanding the activation state and functional interaction of STAT3 and STAT5 in a patient's tumor may be critical for the optimal use of this strategy. PMID:23531638

  14. Selective STAT protein degradation induced by paramyxoviruses requires both STAT1 and STAT2 but is independent of alpha/beta interferon signal transduction.

    PubMed

    Parisien, Jean-Patrick; Lau, Joe F; Rodriguez, Jason J; Ulane, Christina M; Horvath, Curt M

    2002-05-01

    The alpha/beta interferon (IFN-alpha/beta)-induced STAT signal transduction pathway leading to activation of the ISGF3 transcription complex and subsequent antiviral responses is the target of viral pathogenesis strategies. Members of the Rubulavirus genus of the Paramyxovirus family of RNA viruses have acquired the ability to specifically target either STAT1 or STAT2 for proteolytic degradation as a countermeasure for evading IFN responses. While type II human parainfluenza virus induces STAT2 degradation, simian virus 5 induces STAT1 degradation. The components of the IFN signaling system that are required for STAT protein degradation by these paramyxoviruses have been investigated in a series of human somatic cell lines deficient in IFN signaling proteins. Results indicate that neither the IFN-alpha/beta receptor, the tyrosine kinases Jak1 or Tyk2, nor the ISGF3 DNA-binding subunit, IFN regulatory factor 9 (IRF9), is required for STAT protein degradation induced by either virus. Nonetheless, both STAT1 and STAT2 are strictly required in the host cell to establish a degradation-permissive environment enabling both viruses to target their respective STAT protein. Complementation studies reveal that STAT protein-activating tyrosine phosphorylation and functional src homology 2 (SH2) domains are dispensable for creating a permissive STAT degradation environment in degradation-incompetent cells, but the N terminus of the missing STAT protein is essential. Protein-protein interaction analysis indicates that V and STAT proteins interact physically in vitro and in vivo. These results constitute genetic and biochemical evidence supporting a virus-induced, IFN-independent STAT protein degradation complex that contains at least STAT1 and STAT2.

  15. Requirement of Stat3 but not Stat1 activation for epidermal growth factor receptor- mediated cell growth In vitro.

    PubMed Central

    Grandis, J R; Drenning, S D; Chakraborty, A; Zhou, M Y; Zeng, Q; Pitt, A S; Tweardy, D J

    1998-01-01

    Stimulation of epidermal growth factor receptor (EGFR) by ligand(s) leads to activation of signaling molecules including Stat1 and Stat3, two members of the signal transducers and activators of transcription (STAT) protein family. Activation of Stat1 and Stat3 was constitutive in transformed squamous epithelial cells, which produce elevated levels of TGF-alpha, and was enhanced by the addition of exogenous TGF-alpha. Targeting of Stat3 using antisense oligonucleotides directed against the translation initiation site, resulted in significant growth inhibition. In addition, cells stably transfected with dominant negative mutant Stat3 constructs failed to proliferate in vitro. In contrast, targeting of Stat1 using either antisense or dominant-negative strategies had no effect on cell growth. Thus, TGF-alpha/EGFR-mediated autocrine growth of transformed epithelial cells is dependent on activation of Stat3 but not Stat1. PMID:9769331

  16. Different competitive capacities of Stat4- and Stat6-deficient CD4+ T cells during lymphophenia-driven proliferation.

    PubMed

    Sanchez-Guajardo, Vanesa; Borghans, José A M; Marquez, Maria-Elena; Garcia, Sylvie; Freitas, Antonio A

    2005-02-01

    The outcome of an immune response relies on the competitive capacities acquired through differentiation of CD4(+) T cells into Th1 or Th2 effector cells. Because Stat4 and Stat6 proteins are implicated in the Th1 vs Th2 generation and maintenance, respectively, we compare in this study the kinetics of Stat4(-/-) and Stat6(-/-) CD4(+) T cells during competitive bone marrow reconstitution and lymphopenia-driven proliferation. After bone marrow transplantation, both populations reconstitute the peripheral T cell pools equally well. After transfer into lymphopenic hosts, wild-type and Stat6(-/-) CD4(+) T cells show a proliferation advantage, which is early associated with the expression of an active phospho-Stat4 and the down-regulation of Stat6. Despite these differences, Stat4- and Stat6-deficient T cells reach similar steady state numbers. However, when both Stat4(-/-) and Stat6(-/-) CD4(+) T cells are coinjected into the same hosts, the Stat6(-/-) cells become dominant and out-compete Stat4(-/-) cells. These findings suggest that cell activation, through the Stat4 pathway and the down-regulation of Stat6, confers to pro-Th1 T cells a slight proliferation advantage that in a competitive situation has major late repercussions, because it modifies the final homeostatic equilibrium of the populations and favors the establishment of Th1 CD4(+) T cell dominance.

  17. Spirit's Surroundings on Sol 337

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This view was assembled from images taken by the navigation camera on NASA's Mars Exploration Rover Spirit during the rover's 337th martian day, or sol (Dec. 14, 2004). Spirit's position, catalogued as Site 100 for the mission, was on the slope of 'Husband Hill.' The rover had driven 6 meters (20 feet) on Sol 337 after examining a rock called 'Wishstone' for several sols. That rock is just to the left of the top of the arch traced by the rover tracks in this view. Spirit experienced slippage of up to 80 percent on uphill portions of the day's drive. The view is presented here in a cylindrical projection with geometric seam correction.

  18. Opportunity's Surroundings on Sol 1687

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this 360-degree view of the rover's surroundings on the 1,687th Martian day, or sol, of its surface mission (Oct. 22, 2008).

    Opportunity had driven 133 meters (436 feet) that sol, crossing sand ripples up to about 10 centimeters (4 inches) tall. The tracks visible in the foreground are in the east-northeast direction.

    Opportunity's position on Sol 1687 was about 300 meters southwest of Victoria Crater. The rover was beginning a long trek toward a much larger crater, Endeavour, about 12 kilometers (7 miles) to the southeast.

    This view is presented as a cylindrical projection with geometric seam correction.

  19. EXAFS study of PZT sols

    SciTech Connect

    Arcon, Iztok; Malic, Barbara; Kosec, Marija; Kodre, Alojz

    2003-12-10

    The environment of lead atoms in PbZr{sub 0.53}Ti{sub 0.47}O{sub 3} (PZT) sols was analyzed by EXAFS. The sols were prepared by 2-methoxyethanol-route from lead acetate, titanium n-propoxide, and zirconium n-propoxide, either unmodified or modified with acetic acid or acetylacetone. The addition of the modifier evokes the crystallization of the perovskite phase in the films at a lower temperature. In the sols a change in the local Pb environments is observed only after modification with 2 mol of acetylacetone or acetic acid per mole of Zr n-propoxide. With lower amounts of acetylacetone modifier the local Pb neighborhood is not affected.

  20. Sol-gel derived sorbents

    DOEpatents

    Sigman, Michael E.; Dindal, Amy B.

    2003-11-11

    Described is a method for producing copolymerized sol-gel derived sorbent particles for the production of copolymerized sol-gel derived sorbent material. The method for producing copolymerized sol-gel derived sorbent particles comprises adding a basic solution to an aqueous metal alkoxide mixture for a pH.ltoreq.8 to hydrolyze the metal alkoxides. Then, allowing the mixture to react at room temperature for a precalculated period of time for the mixture to undergo an increased in viscosity to obtain a desired pore size and surface area. The copolymerized mixture is then added to an immiscible, nonpolar solvent that has been heated to a sufficient temperature wherein the copolymerized mixture forms a solid upon the addition. The solid is recovered from the mixture, and is ready for use in an active sampling trap or activated for use in a passive sampling trap.

  1. Opportunity's Surroundings on Sol 1818

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,818th Martian day, or sol, of Opportunity's surface mission (March 5, 2009). South is at the center; north at both ends.

    The rover had driven 80.3 meters (263 feet) southward earlier on that sol. Tracks from the drive recede northward in this view.

    The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock.

    This view is presented as a cylindrical projection with geometric seam correction.

  2. STAT2 Is a Pervasive Cytokine Regulator due to Its Inhibition of STAT1 in Multiple Signaling Pathways

    PubMed Central

    Ho, Johnathan; Pelzel, Christin; Begitt, Andreas; Mee, Maureen; Elsheikha, Hany M.; Scott, David J.; Vinkemeier, Uwe

    2016-01-01

    STAT2 is the quintessential transcription factor for type 1 interferons (IFNs), where it functions as a heterodimer with STAT1. However, the human and murine STAT2-deficient phenotypes suggest important additional and currently unidentified type 1 IFN-independent activities. Here, we show that STAT2 constitutively bound to STAT1, but not STAT3, via a conserved interface. While this interaction was irrelevant for type 1 interferon signaling and STAT1 activation, it precluded the nuclear translocation specifically of STAT1 in response to IFN-γ, interleukin-6 (IL-6), and IL-27. This is explained by the dimerization between activated STAT1 and unphosphorylated STAT2, whereby the semiphosphorylated dimers adopted a conformation incapable of importin-α binding. This, in turn, substantially attenuated cardinal IFN-γ responses, including MHC expression, senescence, and antiparasitic immunity, and shifted the transcriptional output of IL-27 from STAT1 to STAT3. Our results uncover STAT2 as a pervasive cytokine regulator due to its inhibition of STAT1 in multiple signaling pathways and provide an understanding of the type 1 interferon-independent activities of this protein. PMID:27780205

  3. Granulin, a novel STAT3-interacting protein, enhances STAT3 transcriptional function and correlates with poorer prognosis in breast cancer

    PubMed Central

    Yeh, Jennifer E.; Kreimer, Simion; Walker, Sarah R.; Emori, Megan M.; Krystal, Hannah; Richardson, Andrea; Ivanov, Alexander R.; Frank, David A.

    2015-01-01

    Since the neoplastic phenotype of a cell is largely driven by aberrant gene expression patterns, increasing attention has been focused on transcription factors that regulate critical mediators of tumorigenesis such as signal transducer and activator of transcription 3 (STAT3). As proteins that interact with STAT3 may be key in addressing how STAT3 contributes to cancer pathogenesis, we took a proteomics approach to identify novel STAT3-interacting proteins. We performed mass spectrometry-based profiling of STAT3-containing complexes from breast cancer cells that have constitutively active STAT3 and are dependent on STAT3 function for survival. We identified granulin (GRN) as a novel STAT3-interacting protein that was necessary for both constitutive and maximal leukemia inhibitory factor (LIF)induced STAT3 transcriptional activity. GRN enhanced STAT3 DNA binding and also increased the time-integrated amount of LIF-induced STAT3 activation in breast cancer cells. Furthermore, silencing GRN neutralized STAT3-mediated tumorigenic phenotypes including viability, clonogenesis, and migratory capacity. In primary breast cancer samples, GRN mRNA levels were positively correlated with STAT3 gene expression signatures and with reduced patient survival. These studies identify GRN as a functionally important STAT3-interacting protein that may serve as an important prognostic biomarker and potential therapeutic target in breast cancer. PMID:26000098

  4. Spirit Drive Animation, Sols 365 to 390

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This animation is built from images taken by the navigation camera on NASA's Mars Exploration Rover Spirit from the rover's 365th martian day, or sol (Jan. 11, 2005), through sol 390 (Feb. 6, 2005). During this period, Spirit covered about 80 meters (262 feet) in its climb toward 'Cumberland Ridge' in the 'Columbia Hills.' The sequence includes images from all of the sols on which Spirit drove during this period: sols 365, 366, 371, 381, 382, 386, 388 and 390.

  5. Sol-Gel Derived Hafnia Coatings

    NASA Technical Reports Server (NTRS)

    Feldman, Jay D.; Stackpoole, Mairead; Blum, Yigal; Sacks, Michael; Ellerby, Don; Johnson, Sylvia M.; Venkatapathy, Ethiras (Technical Monitor)

    2002-01-01

    Sol-gel derived hafnia coatings are being developed to provide an oxidation protection layer on ultra-high temperature ceramics for potential use in turbine engines (ultra-efficient engine technology being developed by NASA). Coatings using hafnia sol hafnia filler particles will be discussed along with sol synthesis and characterization.

  6. Comment on ``Heat transfer in vacuum packaged microelectromechanical system devices'' [Phys. Fluids 20, 017103 (2008)

    NASA Astrophysics Data System (ADS)

    Sone, Yoshio

    2009-11-01

    It is pointed out that the solution of a free molecular gas in a bounded domain proposed as speculation in Sec. II of Cai [Phys. Fluids 20, 017103 (2008)] and in Sec. II of Cai and Liu [Phys. Fluids 20, 067105 (2008)] and its result of the vanishing of flow velocity were rigorously derived under a more general situation and boundary condition more than 20 years ago.

  7. Response to 'Comment on 'Undamped electrostatic plasma waves''[Phys. Plasmas 20, 034701 (2013)

    SciTech Connect

    Valentini, F.; Perrone, D.; Veltri, P.; Califano, F.; Pegoraro, F.; Morrison, P. J.; O'Neil, T. M.

    2013-03-15

    Numerical and experimental evidence is given for the occurrence of the plateau states and concomitant corner modes proposed in Valentini et al.[Phys. Plasmas 19, 092103 (2012)]. It is argued that these states provide a better description of reality for small amplitude off-dispersion disturbances than the conventional Bernstein-Greene-Kruskal or cnoidal states such as those proposed in Schamel [Phys. Plasmas 20, 034701 (2013)].

  8. SOL Tests Create Unfair Pressure.

    ERIC Educational Resources Information Center

    Ernst, Katie

    2000-01-01

    A seventh-grader explains why the Virginia Standards of Learning tests unfairly pressure her and her teachers. She wants her free reading time restored and wishes politicians would worry more about students understanding--not just memorizing--facts. She praises teachers who go beyond the SOL. (MLH)

  9. The SOL: No Easy Answers.

    ERIC Educational Resources Information Center

    Pasi, Raymond

    2000-01-01

    Since the state board adopted the Standards of Learning, Virginia high-school teachers maintain tighter schedules and more often use direct instruction instead of group activities to cover the new curriculum. A two-edged sword, the SOL has engendered an increased interest in professional collaboration. (MLH)

  10. Intramolecular hydrophobic interactions are critical mediators of STAT5 dimerization.

    PubMed

    Fahrenkamp, Dirk; Li, Jinyu; Ernst, Sabrina; Schmitz-Van de Leur, Hildegard; Chatain, Nicolas; Küster, Andrea; Koschmieder, Steffen; Lüscher, Bernhard; Rossetti, Giulia; Müller-Newen, Gerhard

    2016-10-18

    STAT5 is an essential transcription factor in hematopoiesis, which is activated through tyrosine phosphorylation in response to cytokine stimulation. Constitutive activation of STAT5 is a hallmark of myeloid and lymphoblastic leukemia. Using homology modeling and molecular dynamics simulations, a model of the STAT5 phosphotyrosine-SH2 domain interface was generated providing first structural information on the activated STAT5 dimer including a sequence, for which no structural information is available for any of the STAT proteins. We identified a novel intramolecular interaction mediated through F706, adjacent to the phosphotyrosine motif, and a unique hydrophobic interface on the surface of the SH2 domain. Analysis of corresponding STAT5 mutants revealed that this interaction is dispensable for Epo receptor-mediated phosphorylation of STAT5 but essential for dimer formation and subsequent nuclear accumulation. Moreover, the herein presented model clarifies molecular mechanisms of recently discovered leukemic STAT5 mutants and will help to guide future drug development.

  11. Mitochondrial Stat3, the Need for Design Thinking

    PubMed Central

    Yang, Rui; Rincon, Mercedes

    2016-01-01

    Stat3 has been studied extensively as a transcription factor, however the finding that Stat3 also localizes to mitochondria has opened a new area to discover non-classical functions. Here we review the current knowledge of mitochondrial Stat3 as a regulator of the electron transport chain (ETC) and its impact on mitochondrial production of ATP and ROS. We also describe recent findings identifying Stat3 as a regulator of mitochondrial Ca2+ homeostasis through its effect on the ETC. It is becoming evident that these non-classical functions of Stat3 can have a major impact on cancer progression, cardiovascular diseases, and inflammatory diseases. Therefore, mitochondrial Stat3 functions challenge the current design of therapies that solely target Stat3 as a transcription factor and suggest the need for “design thinking,” which leads to the development of novel strategies, to intervene the Stat3 pathway. PMID:27019635

  12. Intramolecular hydrophobic interactions are critical mediators of STAT5 dimerization

    NASA Astrophysics Data System (ADS)

    Fahrenkamp, Dirk; Li, Jinyu; Ernst, Sabrina; Schmitz-van de Leur, Hildegard; Chatain, Nicolas; Küster, Andrea; Koschmieder, Steffen; Lüscher, Bernhard; Rossetti, Giulia; Müller-Newen, Gerhard

    2016-10-01

    STAT5 is an essential transcription factor in hematopoiesis, which is activated through tyrosine phosphorylation in response to cytokine stimulation. Constitutive activation of STAT5 is a hallmark of myeloid and lymphoblastic leukemia. Using homology modeling and molecular dynamics simulations, a model of the STAT5 phosphotyrosine-SH2 domain interface was generated providing first structural information on the activated STAT5 dimer including a sequence, for which no structural information is available for any of the STAT proteins. We identified a novel intramolecular interaction mediated through F706, adjacent to the phosphotyrosine motif, and a unique hydrophobic interface on the surface of the SH2 domain. Analysis of corresponding STAT5 mutants revealed that this interaction is dispensable for Epo receptor-mediated phosphorylation of STAT5 but essential for dimer formation and subsequent nuclear accumulation. Moreover, the herein presented model clarifies molecular mechanisms of recently discovered leukemic STAT5 mutants and will help to guide future drug development.

  13. Intramolecular hydrophobic interactions are critical mediators of STAT5 dimerization

    PubMed Central

    Fahrenkamp, Dirk; Li, Jinyu; Ernst, Sabrina; Schmitz-Van de Leur, Hildegard; Chatain, Nicolas; Küster, Andrea; Koschmieder, Steffen; Lüscher, Bernhard; Rossetti, Giulia; Müller-Newen, Gerhard

    2016-01-01

    STAT5 is an essential transcription factor in hematopoiesis, which is activated through tyrosine phosphorylation in response to cytokine stimulation. Constitutive activation of STAT5 is a hallmark of myeloid and lymphoblastic leukemia. Using homology modeling and molecular dynamics simulations, a model of the STAT5 phosphotyrosine-SH2 domain interface was generated providing first structural information on the activated STAT5 dimer including a sequence, for which no structural information is available for any of the STAT proteins. We identified a novel intramolecular interaction mediated through F706, adjacent to the phosphotyrosine motif, and a unique hydrophobic interface on the surface of the SH2 domain. Analysis of corresponding STAT5 mutants revealed that this interaction is dispensable for Epo receptor-mediated phosphorylation of STAT5 but essential for dimer formation and subsequent nuclear accumulation. Moreover, the herein presented model clarifies molecular mechanisms of recently discovered leukemic STAT5 mutants and will help to guide future drug development. PMID:27752093

  14. Exploring dual inhibitors for STAT1 and STAT5 receptors utilizing virtual screening and dynamics simulation validation.

    PubMed

    Raj, Utkarsh; Kumar, Himansu; Gupta, Saurabh; Varadwaj, Pritish Kumar

    2016-10-01

    Signal transducer and activator of transcription (STAT) proteins are latent cytoplasmic transcription factors that transduce signals from cytokines and growth factors to the nucleus and thereby regulate the expression of a variety of target genes. Although mutations of STATs have not been reported in human tumors but the activity of several members of the family, such as STAT1 and STAT5, is deregulated in a variety of human carcinoma. STAT1 and STAT5 share a structural similarity with a highly conserved SH2 domain which is responsible for the activation of STAT proteins on interaction with phosphotyrosine motifs for specific STAT-receptor contacts and STAT dimerization. The purpose of this study is to identify domain-specific dual inhibitors for both STAT1 and STAT5 proteins from a database of natural products and natural product-like compounds comprising of over 90,000 compounds. Virtual screening-based molecular docking was performed in order to find novel natural dual inhibitors. Further, the study was supported by the 50-ns molecular dynamics simulation for receptor-ligand complexes (STAT1-STOCK-1N-69677 and STAT5-STOCK-1N-69677). Analysis of molecular interactions in the SH2 domains of both STAT1 and STAT5 proteins with the ligand revealed few conserved amino acid residues which are responsible to stabilize the ligands within the binding pocket through bonded and non-bonded interactions. This study suggested that compound STOCK-1N-69677 might putatively act as a dual inhibitor of STAT1 and STAT5 receptors, through its binding to the SH2 domain.

  15. An SH2 domain model of STAT5 in complex with phospho-peptides define ``STAT5 Binding Signatures''

    NASA Astrophysics Data System (ADS)

    Gianti, Eleonora; Zauhar, Randy J.

    2015-05-01

    The signal transducer and activator of transcription 5 (STAT5) is a member of the STAT family of proteins, implicated in cell growth and differentiation. STAT activation is regulated by phosphorylation of protein monomers at conserved tyrosine residues, followed by binding to phospho-peptide pockets and subsequent dimerization. STAT5 is implicated in the development of severe pathological conditions, including many cancer forms. However, nowadays a few STAT5 inhibitors are known, and only one crystal structure of the inactive STAT5 dimer is publicly available. With a view to enabling structure-based drug design, we have: (1) analyzed phospho-peptide binding pockets on SH2 domains of STAT5, STAT1 and STAT3; (2) generated a model of STAT5 bound to phospho-peptides; (3) assessed our model by docking against a class of known STAT5 inhibitors (Müller et al. in ChemBioChem 9:723-727, 2008); (4) used molecular dynamics simulations to optimize the molecular determinants responsible for binding and (5) proposed unique "Binding Signatures" of STAT5. Our results put in place the foundations to address STAT5 as a target for rational drug design, from sequence, structural and functional perspectives.

  16. Solar Technical Assistance Team (STAT) (Fact Sheet)

    SciTech Connect

    Not Available

    2014-05-01

    The Solar Technical Assistance Team (STAT) is a team of solar technology and deployment experts who ensure that the best information on policies, regulations, financing, and other issues is getting into the hands of state government decision makers when they need it.

  17. STAT3 Activities and Energy Metabolism: Dangerous Liaisons

    PubMed Central

    Camporeale, Annalisa; Demaria, Marco; Monteleone, Emanuele; Giorgi, Carlotta; Wieckowski, Mariusz R.; Pinton, Paolo; Poli, Valeria

    2014-01-01

    STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3C/C) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3C/C MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3C/C MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms. PMID:25089666

  18. Statistical Inference and Simulation with StatKey

    ERIC Educational Resources Information Center

    Quinn, Anne

    2016-01-01

    While looking for an inexpensive technology package to help students in statistics classes, the author found StatKey, a free Web-based app. Not only is StatKey useful for students' year-end projects, but it is also valuable for helping students learn fundamental content such as the central limit theorem. Using StatKey, students can engage in…

  19. Therapeutic modulators of STAT signalling for human diseases

    PubMed Central

    Miklossy, Gabriella; Hilliard, Tyvette S.; Turkson, James

    2014-01-01

    The signal transducer and activator of transcription (STAT) proteins have important roles in biological processes. The abnormal activation of STAT signalling pathways is also implicated in many human diseases, including cancer, autoimmune diseases, rheumatoid arthritis, asthma and diabetes. Over a decade has passed since the first inhibitor of a STAT protein was reported and efforts to discover modulators of STAT signalling as therapeutics continue. This Review discusses the outcomes of the ongoing drug discovery research endeavours against STAT proteins, provides perspectives on new directions for accelerating the discovery of drug candidates, and highlights the noteworthy candidate therapeutics that have progressed to clinical trials. PMID:23903221

  20. Opportunity's Surroundings on Sol 1798

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this 180-degree view of the rover's surroundings during the 1,798th Martian day, or sol, of Opportunity's surface mission (Feb. 13, 2009). North is on top.

    The rover had driven 111 meters (364 feet) southward on the preceding sol. Tracks from that drive recede northward in this view. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches).

    The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock.

    This view is presented as a cylindrical projection with geometric seam correction.

  1. Nanocrystal/sol-gel nanocomposites

    DOEpatents

    Klimov, Victor L.; Petruska, Melissa A.

    2010-05-25

    The present invention is directed to a process for preparing a solid composite having colloidal nanocrystals dispersed within a sol-gel matrix, the process including admixing colloidal nanocrystals with an amphiphilic polymer including hydrophilic groups selected from the group consisting of --COOH, --OH, --SO.sub.3H, --NH.sub.2, and --PO.sub.3H.sub.2 within a solvent to form an alcohol-soluble colloidal nanocrystal-polymer complex, admixing the alcohol-soluble colloidal nanocrystal-polymer complex and a sol-gel precursor material, and, forming the solid composite from the admixture. The present invention is also directed to the resultant solid composites and to the alcohol-soluble colloidal nanocrystal-polymer complexes.

  2. Spirit's Surroundings on Sol 337

    NASA Technical Reports Server (NTRS)

    2004-01-01

    [figure removed for brevity, see original site] Figure 1

    [figure removed for brevity, see original site] Figure 2

    This stereo view was assembled from images taken by the navigation camera on NASA's Mars Exploration Rover Spirit during the rover's 337th martian day, or sol (Dec. 14, 2004). Spirit's position, catalogued as Site 100 for the mission, was on the slope of 'Husband Hill.' The rover had driven 6 meters (20 feet) on Sol 337 after examining a rock called 'Wishstone' for several sols. That rock is just to the left of the top of the arch traced by the rover tracks in this view. Spirit experienced slippage of up to 80 percent on uphill portions of the day's drive. The view is presented here in a cylindrical-perspective projection with geometric seam correction.

    Figure 1 is the left-eye view of a stereo pair and Figure 2 is the right-eye view of a stereo pair.

  3. Metal-silica sol-gel materials

    NASA Technical Reports Server (NTRS)

    Stiegman, Albert E. (Inventor)

    2002-01-01

    The present invention relates to a single phase metal-silica sol-gel glass formed by the co-condensation of a transition metal with silicon atoms where the metal atoms are uniformly distributed within the sol-gel glass as individual metal centers. Any transition metal may be used in the sol-gel glasses. The present invention also relates to sensor materials where the sensor material is formed using the single phase metal-silica sol-gel glasses. The sensor materials may be in the form of a thin film or may be attached to an optical fiber. The present invention also relates to a method of sensing chemicals using the chemical sensors by monitoring the chromatic change of the metal-silica sol-gel glass when the chemical binds to the sensor. The present invention also relates to oxidation catalysts where a metal-silica sol-gel glass catalyzes the reaction. The present invention also relates to a method of performing oxidation reactions using the metal-silica sol-gel glasses. The present invention also relates to organopolymer metal-silica sol-gel composites where the pores of the metal-silica sol-gel glasses are filled with an organic polymer polymerized by the sol-gel glass.

  4. Molecular imprinting in sol-gel matrix.

    PubMed

    Gupta, Radha; Kumar, Ashok

    2008-01-01

    Molecular imprinting is a newly developed methodology which provides molecular assemblies of desired structures and properties and is being increasingly used for several applications such as in separation processes, microreactors, immunoassays and antibody mimics, catalysis, artificial enzymes, biosensor recognition elements and bio- and chemo-sensors. The ambient processing conditions and versatility of the sol-gel process makes sol-gel glassy matrix suitable for molecular imprinting. The progress of sol-gel based molecular imprinted polymers (MIPs) for various applications can be seen from the growing number of publications. The main focus of the review is molecular imprinting in sol-gel matrix and applications of molecular imprinted sol-gel derived materials for the development of sensors. Combining sol-gel process with molecular imprinting enables to procure the sensors with greater sensitivity and selectivity necessary for sensing applications. The merits, problems, challenges and factors affecting molecular imprinting in sol-gel matrix have been discussed. Considerable attention has been drawn on recent developments like use of organically modified silane precursors (ORMOSILS) for the synthesis of hybrid molecular imprinted polymers (HMIPs) and applying surface sol-gel process for molecular imprinting. The development of molecular imprinted sol-gel nanotubes for biochemical separation and bio-imprinting is a new advancement and is under progress. Templated xerogels and molecularly imprinted sol-gel films provide a good platform for various sensor applications.

  5. STAT1 acts as a tumor promoter for leukemia development.

    PubMed

    Kovacic, Boris; Stoiber, Dagmar; Moriggl, Richard; Weisz, Eva; Ott, René G; Kreibich, Rita; Levy, David E; Beug, Hartmut; Freissmuth, Michael; Sexl, Veronika

    2006-07-01

    The tumor suppressor STAT1 is considered a key regulator of the surveillance of developing tumors. Here, we describe an unexpected tumor-promoting role for STAT1 in leukemia. STAT1(-/-) mice are partially protected from leukemia development, and STAT1(-/-) tumor cells induce leukemia in RAG2(-/-) and immunocompetent mice with increased latency. The low MHC class I protein levels of STAT1(-/-) tumor cells enable efficient NK cell lysis and account for the enhanced tumor clearance. Strikingly, STAT1(-/-) tumor cells acquire increased MHC class I expression upon leukemia progression. These findings define STAT1 as a tumor promoter in leukemia development. Furthermore, we describe the upregulation of MHC class I expression as a general mechanism that allows for the escape of hematopoietic malignancies from immune surveillance.

  6. Solar Technical Assistance Team (STAT) (Fact Sheet)

    SciTech Connect

    Not Available

    2011-03-01

    The Solar Technical Assistance Team (STAT) is a team of solar technology and deployment experts who ensure that the best information on policies, regulations, financing and other issues is getting into the hands of state government decision makers at the time they need it. The goal of the team is to provide timely, unbiased expertise to assist key policy makers and regulators in making informed decisions.

  7. Inhibition of STAT3 activation by KT-18618 via the disruption of the interaction between JAK3 and STAT3.

    PubMed

    Shin, Dae-Seop; Jung, Seung Nam; Yun, Jieun; Lee, Chang Woo; Han, Dong Cho; Kim, Bumtae; Min, Yong Ki; Kang, Nam Sook; Kwon, Byoung-Mog

    2014-05-01

    The constitutive activation of STAT3 in human cancers causes the abnormal proliferation and survival of cancer cells, and thus, STAT3 is a therapeutic target of antitumor drugs. We screened a small-molecule library of 8600 synthetic compounds from the "Korea Chemical Bank" to identify inhibit STAT3 activity using a cell-based luciferase assay system. KT-18618 ((Z)-N-(4-chlorophenyl)-N-methyl-2-[1,3,3,3,-tetrafluoro-2-(thiophen-2-yl)prop-1-enyloxy]-acetamide) was selected as a novel inhibitor of the JAK/STAT3 pathway. KT-18618 inhibited STAT3 phosphorylation and the expression of STAT3-regulated genes. The inhibition of STAT3 phosphorylation led to the apoptosis of MDA-MB-468 cells. We postulated that the inhibition of the JAK family of proteins or c-Src inhibited STAT3 phosphorylation. Interestingly, the phosphorylation of these kinases was only mildly inhibited, but the phosphorylation of STAT3 was completely inhibited. This result implies that the inhibition of STAT3 phosphorylation by KT-18618 is an independent event that occurs through the phosphorylation of upstream kinases. Co-immunoprecipitation experiments revealed that KT-18618 inhibited the JAK3-STAT3 interaction. Moreover, JAK3 molecules were captured by biotinylated KT-18618, implying that KT-18618 bound to JAK3 molecules. Additionally, 1μM KT-18618 inhibited JAK3 kinase activity by approximately 28% in an in vitro kinase assay. From these results, we suggest that KT-18618 binds to JAK3 molecules and disrupts the JAK3-STAT3 interaction, which leads to the inhibition of STAT3 phosphorylation. KT-18618 is the first inhibitor of the JAK3-STAT3 interaction.

  8. Distal regulatory element of the STAT1 gene potentially mediates positive feedback control of STAT1 expression.

    PubMed

    Yuasa, Katsutoshi; Hijikata, Takao

    2016-01-01

    We previously identified a distal regulatory element located approximately 5.5-kb upstream of the signal transducer and activator of transcription 1 (STAT1) gene, thereafter designating it as 5.5-kb upstream regulatory region (5.5URR). In this study, we investigated the functional roles of 5.5URR in the transcriptional regulation of STAT1 gene. A chromosome conformation capture assay indicated physical interaction of 5.5URR with the STAT1 core promoter. In luciferase reporter assays, 5.5URR-combined STAT1 core promoter exhibited significant increase in reporter activity enhanced by forced STAT1 expression or interferon (IFN) treatment, but STAT1 core promoter alone did not. The 5.5URR contained IFN-stimulated response element and GAS sites, which bound STAT1 complexes in electrophoretic mobility shift assays. Consistently, chromatin immunoprecipitation (ChIP) assays of HEK293 cells with Halo-tagged STAT1 expression indicated the association of Halo-tagged STAT1 with 5.5URR. ChIP assays with IFN treatment demonstrated that IFNs promoted the recruitment of Halo-tagged STAT1 to 5.5URR. Forced STAT1 expression or IFN treatment increased the expression of endogenous STAT1 and other IFN signaling pathway components, such as STAT2, IRF9 and IRF1, besides IFN-responsive genes. Collectively, the results suggest that 5.5URR may provide a regulatory platform for positive feedback control of STAT1 expression possibly to amplify or sustain the intracellular IFN signals.

  9. Interaction of mumps virus V protein variants with STAT1-STAT2 heterodimer: experimental and theoretical studies

    PubMed Central

    2010-01-01

    Background Mumps virus V protein has the ability to inhibit the interferon-mediated antiviral response by inducing degradation of STAT proteins. Two virus variants purified from Urabe AM9 mumps virus vaccine differ in their replication and transcription efficiency in cells primed with interferon. Virus susceptibility to IFN was associated with insertion of a non-coded glycine at position 156 in the V protein (VGly) of one virus variant, whereas resistance to IFN was associated with preservation of wild-type phenotype in the V protein (VWT) of the other variant. Results VWT and VGly variants of mumps virus were cloned and sequenced from Urabe AM9 vaccine strain. VGly differs from VWT protein because it possesses an amino acid change Gln103Pro (Pro103) and the Gly156 insertion. The effect of V protein variants on components of the interferon-stimulated gene factor 3 (ISGF3), STAT1 and STAT2 proteins were experimentally tested in cervical carcinoma cell lines. Expression of VWT protein decreased STAT1 phosphorylation, whereas VGly had no inhibitory effect on either STAT1 or STAT2 phosphorylation. For theoretical analysis of the interaction between V proteins and STAT proteins, 3D structural models of VWT and VGly were predicted by comparing with simian virus 5 (SV5) V protein structure in complex with STAT1-STAT2 heterodimer. In silico analysis showed that VWT-STAT1-STAT2 complex occurs through the V protein Trp-motif (W174, W178, W189) and Glu95 residue close to the Arg409 and Lys415 of the nuclear localization signal (NLS) of STAT2, leaving exposed STAT1 Lys residues (K85, K87, K296, K413, K525, K679, K685), which are susceptible to proteasome degradation. In contrast, the interaction between VGly and STAT1-STAT2 heterodimer occurs in a region far from the NLS of STAT2 without blocking of Lys residues in both STAT1 and STAT2. Conclusions Our results suggest that VWT protein of Urabe AM9 strain of mumps virus may be more efficient than VGly to inactivate both the IFN

  10. Comment on: “Quantum exam” [Phys. Lett. A 350 (2006) 174

    NASA Astrophysics Data System (ADS)

    Song, Jie; Zhang, Shou

    2007-01-01

    In the Letter [B.A. Nguyen, Phys. Lett. A 350 (2006) 174], a quantum exam protocol was presented. Here we show a cheating protocol, by which any student can get the other students' solution without being detected. Then we propose a possible modified protocol against this attacking strategy.

  11. Comment on ``Derivation of paleoclassical key hypothesis'' [Phys. Plasmas 14, 040701 (2007)

    NASA Astrophysics Data System (ADS)

    Thyagaraja, A.; Roach, C. M.; Hazeltine, R. D.

    2008-01-01

    The paleoclassical hypothesis, derived in Callen [Phys. Plasmas 14, 040701 (2007)], proposes that electron guiding centers experience additional diffusion which is absent from neoclassical theory. This is claimed to be associated with the diffusion of poloidal magnetic flux, and to be most significant in cold resistive plasmas. In this comment we explain why the paleoclassical hypothesis contradicts electrodynamics.

  12. Targeting STAT3 in cancer: how successful are we?

    PubMed Central

    Yue, Peibin; Turkson, James

    2008-01-01

    Background Aberrant activation of the signal transducer and activator of transcription (STAT)3 occurs in many human tumors. Moreover, studies utilizing genetic and pharmacological approaches to modulate constitutive STAT3 activity have provided compelling evidence for the critical role of aberrant STAT3 activity in malignant transformation and tumor progression, and thereby validated STAT3 as a novel cancer drug target. Objective This review is intended to be a full coverage of the efforts to develop direct STAT3 inhibitors and will provide a discussion on the inhibitory modalities developed to date. Methods Review of the literature focused on the modalities and mechanisms that directly target and inhibit the STAT protein or its functions. Results/conclusion While a variety of STAT3 inhibitors have been identified that induce antitumor cell effects in vitro and in vivo, the landscape remains murky. With a few exceptions, most of the STAT3 inhibitors reported to date have not undergone an in vivo efficacy, pharmacology or toxicity testing. Also, there is no evidence, per the published literature of an impending clinical development for the few agents that were reported to exhibit in vivo efficacy. Overall, there is the need for a reassessment of the ongoing strategies to target STAT3 intended not only for refinement, but also for incorporating some new technologies to strengthen our efforts and ensure the success – sooner, rather than later – of identifying suitable anti-STAT3 agents for development into clinically useful anticancer therapeutics. PMID:19053881

  13. Hybrid sol-gel optical materials

    DOEpatents

    Zeigler, J.M.

    1993-04-20

    Hybrid sol-gel materials comprise silicate sols cross-linked with linear polysilane, polygermane, or poly(silane-germane). The sol-gel materials are useful as optical identifiers in tagging and verification applications and, in a different aspect, as stable, visible light transparent non-linear optical materials. Methyl or phenyl silicones, polyaryl sulfides, polyaryl ethers, and rubbery polysilanes may be used in addition to the linear polysilane. The linear polymers cross-link with the sol to form a matrix having high optical transparency, resistance to thermooxidative aging, adherence to a variety of substrates, brittleness, and a resistance to cracking during thermal cycling.

  14. Hybrid sol-gel optical materials

    DOEpatents

    Zeigler, John M.

    1993-01-01

    Hybrid sol-gel materials comprise silicate sols cross-linked with linear polysilane, polygermane, or poly(silane-germane). The sol-gel materials are useful as optical identifiers in tagging and verification applications and, in a different aspect, as stable, visible light transparent non-linear optical materials. Methyl or phenyl silicones, polyaryl sulfides, polyaryl ethers, and rubbery polysilanes may be used in addition to the linear polysilane. The linear polymers cross-link with the sol to form a matrix having high optical transparency, resistance to thermooxidative aging, adherence to a variety of substrates, brittleness, and a resistance to cracking during thermal cycling.

  15. Hybrid sol-gel optical materials

    DOEpatents

    Zeigler, John M.

    1992-01-01

    Hybrid sol-gel materials comprise silicate sols cross-linked with linear polysilane, polygermane, or poly(silane-germane). The sol-gel materials are useful as optical identifiers in tagging and verification applications and, in a different aspect, as stable, visible light transparent non-linear optical materials. Methyl or phenyl silicones, polyaryl sulfides, polyaryl ethers, and rubbery polysilanes may be used in addition to the linear polysilane. The linear polymers cross-link with the sol to form a matrix having high optical transparency, resistance to thermooxidative aging, adherence to a variety of substrates, brittleness, and a resistance to cracking during thermal cycling.

  16. SOL - SIZING AND OPTIMIZATION LANGUAGE COMPILER

    NASA Technical Reports Server (NTRS)

    Scotti, S. J.

    1994-01-01

    SOL is a computer language which is geared to solving design problems. SOL includes the mathematical modeling and logical capabilities of a computer language like FORTRAN but also includes the additional power of non-linear mathematical programming methods (i.e. numerical optimization) at the language level (as opposed to the subroutine level). The language-level use of optimization has several advantages over the traditional, subroutine-calling method of using an optimizer: first, the optimization problem is described in a concise and clear manner which closely parallels the mathematical description of optimization; second, a seamless interface is automatically established between the optimizer subroutines and the mathematical model of the system being optimized; third, the results of an optimization (objective, design variables, constraints, termination criteria, and some or all of the optimization history) are output in a form directly related to the optimization description; and finally, automatic error checking and recovery from an ill-defined system model or optimization description is facilitated by the language-level specification of the optimization problem. Thus, SOL enables rapid generation of models and solutions for optimum design problems with greater confidence that the problem is posed correctly. The SOL compiler takes SOL-language statements and generates the equivalent FORTRAN code and system calls. Because of this approach, the modeling capabilities of SOL are extended by the ability to incorporate existing FORTRAN code into a SOL program. In addition, SOL has a powerful MACRO capability. The MACRO capability of the SOL compiler effectively gives the user the ability to extend the SOL language and can be used to develop easy-to-use shorthand methods of generating complex models and solution strategies. The SOL compiler provides syntactic and semantic error-checking, error recovery, and detailed reports containing cross-references to show where

  17. Spirit Sol 154, Driving By

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This image was taken by NASA's Mars Exploration Rover Spirit's front hazard avoidance camera during Spirit's 154th martian day, or sol, on June 9, 2004. The 'Columbia Hills' appear against the horizon. Directly in front of the rover is the highest of the hills, 'Husband Hill,' approximately 90 meters (295 feet) tall. The rock in the foreground is larger than other surrounding rocks, approximately 35 centimeters (14 inches) across, but was not an observation target for Spirit. The tread marks in front of the rock are not a trench, but simply evidence that the rover passed by as it continued its journey toward the Columbia Hills.

  18. Photorefractive sol-gel materials

    SciTech Connect

    Chaput, F.; Boilot, J.P.; Gacoin, T.; Darracq, B.; Riehl, D.; Canva, M.; Levy, Y.; Brun, A.

    1996-12-31

    The authors report the synthesis and characterization of photorefractive sol-gel materials that possess covalently attached push-pull azobenzene and carbazole moieties. Molecular structural characterization of the modified silane monomers was achieved by {sup 1}H NMR and infra red spectroscopy. The second-order nonlinear optical properties of the organic-inorganic hybrid films prepared from modified silane monomers were evaluated by second-harmonic generation. The stabilized value of the second harmonic coefficient, d{sub 33}, of films poled by corona discharge, at 1,064 nm fundamental wavelength was found to be 107 pm/V. Photorefractivity was clearly displayed from a two beam coupling experiment.

  19. Mutations in the linker domain affect phospho-STAT3 function and suggest targets for interrupting STAT3 activity.

    PubMed

    Mertens, Claudia; Haripal, Bhagwattie; Klinge, Sebastian; Darnell, James E

    2015-12-01

    Crystallography of the cores of phosphotyrosine-activated dimers of STAT1 (132-713) and STAT3 (127-722) bound to a similar double-stranded deoxyoligonucleotide established the domain structure of the STATs and the structural basis for activation through tyrosine phosphorylation and dimerization. We reported earlier that mutants in the linker domain of STAT1 that connect the DNA-binding domain and SH2 domain can prevent transcriptional activation. Because of the pervasive importance of persistently activated STAT3 in many human cancers and the difficulty of finding useful drug candidates aimed at disrupting the pY interchange in active STAT3 dimers, we have examined effects of an array of mutants in the STAT3 linker domain. We have found several STAT3 linker domain mutants to have profound effects of inhibiting STAT3 transcriptional activation. From these results, we propose (i) there is definite functional interaction of the linker both with the DNA binding domain and with the SH2 domain, and (ii) these putative contacts provide potential new targets for small molecule-induced pSTAT3 inhibition.

  20. Mutations in the linker domain affect phospho-STAT3 function and suggest targets for interrupting STAT3 activity

    PubMed Central

    Mertens, Claudia; Haripal, Bhagwattie; Klinge, Sebastian; Darnell, James E.

    2015-01-01

    Crystallography of the cores of phosphotyrosine-activated dimers of STAT1 (132–713) and STAT3 (127–722) bound to a similar double-stranded deoxyoligonucleotide established the domain structure of the STATs and the structural basis for activation through tyrosine phosphorylation and dimerization. We reported earlier that mutants in the linker domain of STAT1 that connect the DNA-binding domain and SH2 domain can prevent transcriptional activation. Because of the pervasive importance of persistently activated STAT3 in many human cancers and the difficulty of finding useful drug candidates aimed at disrupting the pY interchange in active STAT3 dimers, we have examined effects of an array of mutants in the STAT3 linker domain. We have found several STAT3 linker domain mutants to have profound effects of inhibiting STAT3 transcriptional activation. From these results, we propose (i) there is definite functional interaction of the linker both with the DNA binding domain and with the SH2 domain, and (ii) these putative contacts provide potential new targets for small molecule-induced pSTAT3 inhibition. PMID:26553978

  1. Role of STAT3 in Cancer Metastasis and Translational Advances

    PubMed Central

    Patil, Prachi; Gude, Rajiv P.

    2013-01-01

    Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. It is activated by tyrosine phosphorylation at position 705 leading to its dimerization, nuclear translocation, DNA binding, and activation of gene transcription. Under normal physiological conditions, STAT3 activation is tightly regulated. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a pivotal role in tumor growth and metastasis. It regulates cellular proliferation, invasion, migration, and angiogenesis that are critical for cancer metastasis. In this paper, we first describe the mechanism of STAT3 regulation followed by how STAT3 is involved in cancer metastasis, then we summarize the various small molecule inhibitors that inhibit STAT3 signaling. PMID:24199193

  2. JAK-STAT signaling and myocardial glucose metabolism

    PubMed Central

    Frias, Miguel A; Montessuit, Christophe

    2013-01-01

    JAK-STAT signaling occurs in virtually every tissue of the body, and so does glucose metabolism. In this review, we summarize the regulation of glucose metabolism in the myocardium and ponder whether JAK-STAT signaling participates in this regulation. Despite a paucity of data directly pertaining to cardiac myocytes, we conclude that JAK-STAT signaling may contribute to the development of insulin resistance in the myocardium in response to various hormones and cytokines. PMID:24416656

  3. Structural Tailoring of Advanced Turboprops (STAT) programmer's manual

    NASA Technical Reports Server (NTRS)

    Brown, K. W.; Harvey, P. R.

    1989-01-01

    The Structural Tailoring of Advanced Turboprops (STAT) computer program was developed to perform numerical optimizations on highly swept propfan blades. This manual describes the functionality of the STAT system from a programmer's viewpoint. It provides a top-down description of module intent and interaction. The purpose of this manual is to familiarize the programmer with the STAT system should he/she wish to enhance or verify the program's function.

  4. STAT3 in Cancer—Friend or Foe?

    PubMed Central

    Zhang, Hai-Feng; Lai, Raymond

    2014-01-01

    The roles and significance of STAT3 in cancer biology have been extensively studied for more than a decade. Mounting evidence has shown that constitutive activation of STAT3 is a frequent biochemical aberrancy in cancer cells, and this abnormality directly contributes to tumorigenesis and shapes many malignant phenotypes in cancer cells. Nevertheless, results from more recent experimental and clinicopathologic studies have suggested that STAT3 also can exert tumor suppressor effects under specific conditions. Importantly, some of these studies have demonstrated that STAT3 can function either as an oncoprotein or a tumor suppressor in the same cell type, depending on the specific genetic background or presence/absence of specific coexisting biochemical defects. Thus, in the context of cancer biology, STAT3 can be a friend or foe. In the first half of this review, we will highlight the “evil” features of STAT3 by summarizing its oncogenic functions and mechanisms. The differences between the canonical and non-canonical pathway will be highlighted. In the second half, we will summarize the evidence supporting that STAT3 can function as a tumor suppressor. To explain how STAT3 may mediate its tumor suppressor effects, we will discuss several possible mechanisms, one of which is linked to the role of STAT3β, one of the two STAT3 splicing isoforms. Taken together, it is clear that the roles of STAT3 in cancer are multi-faceted and far more complicated than one appreciated previously. The new knowledge has provided us with new approaches and strategies when we evaluate STAT3 as a prognostic biomarker or therapeutic target. PMID:24995504

  5. STAT4 deficiency reduces the development of atherosclerosis in mice.

    PubMed

    Taghavie-Moghadam, Parésa L; Gjurich, Breanne N; Jabeen, Rukhsana; Krishnamurthy, Purna; Kaplan, Mark H; Dobrian, Anca D; Nadler, Jerry L; Galkina, Elena V

    2015-11-01

    Atherosclerosis is a chronic inflammatory process that leads to plaque formation in large and medium sized vessels. T helper 1 (Th1) cells constitute the majority of plaque infiltrating pro-atherogenic T cells and are induced via IFNγ-dependent activation of T-box (Tbet) and/or IL-12-dependent activation of signal transducer and activator of transcription 4 (STAT4). We thus aimed to define a role for STAT4 in atherosclerosis. STAT4-deficiency resulted in a ∼71% reduction (p < 0.001) in plaque burden in Stat4(-/-)Apoe(-/-) vs Apoe(-/-) mice fed chow diet and significantly attenuated atherosclerosis (∼31%, p < 0.01) in western diet fed Stat4(-/-)Apoe(-/-) mice. Surprisingly, reduced atherogenesis in Stat4(-/-)Apoe(-/-) mice was not due to attenuated IFNγ production in vivo by Th1 cells, suggesting an at least partially IFNγ-independent pro-atherogenic role of STAT4. STAT4 is expressed in T cells, but also detected in macrophages (MΦs). Stat4(-/-)Apoe(-/-)in vitro differentiated M1 or M2 MΦs had reduced cytokine production compare to Apoe(-/-) M1 and M2 MΦs that was accompanied by reduced induction of CD69, I-A(b), and CD86 in response to LPS stimulation. Stat4(-/-)Apoe(-/-) MΦs expressed attenuated levels of CCR2 and demonstrated reduced migration toward CCL2 in a transwell assay. Importantly, the percentage of aortic CD11b(+)F4/80(+)Ly6C(hi) MΦs was reduced in Stat4(-/-)Apoe(-/-) vs Apoe(-/-) mice. Thus, this study identifies for the first time a pro-atherogenic role of STAT4 that is at least partially independent of Th1 cell-derived IFNγ, and primarily involving the modulation of MΦ responses.

  6. Radiosensitization by Inhibiting STAT1 in Renal Cell Carcinoma

    SciTech Connect

    Hui Zhouguang; Tretiakova, Maria; Zhang Zhongfa; Li Yan; Wang Xiaozhen; Zhu, Julie Xiaohong; Gao Yuanhong; Mai Weiyuan; Furge, Kyle; Qian Chaonan; Amato, Robert; Butler, E. Brian

    2009-01-01

    Purpose: Renal cell carcinoma (RCC) has been historically regarded as a radioresistant malignancy, but the molecular mechanism underlying its radioresistance is not understood. This study investigated the role of signal transducer and activator of transcription 1 (STAT1), a transcription factor downstream of the interferon-signaling pathway, in radioresistant RCC. Methods and Materials: The expressions of STAT1 and STAT3 in 164 human clear cell RCC samples, 47 papillary RCC samples, and 15 normal kidney tissue samples were examined by microarray expression profiling and immunohistochemistry. Western blotting was performed to evaluate the total and phosphorylated STAT1 expression in CRL-1932 (786-O) (human clear cell RCC), SKRC-39 (human papillary RCC), CCL-116 (human fibroblast), and CRL-1441 (G-401) (human Wilms tumor). STAT1 was reduced or inhibited by fludarabine and siRNA, respectively, and the effects on radiation-induced cell death were investigated using clonogenic assays. Results: STAT1 expression, but not STAT3 expression, was significantly greater in human RCC samples (p = 1.5 x 10{sup -8} for clear cell; and p = 3.6 x 10{sup -4} for papillary). Similarly, the expression of STAT1 was relatively greater in the two RCC cell lines. STAT1 expression was reduced by both fludarabine and siRNA, significantly increasing the radiosensitivity in both RCC cell lines. Conclusion: This is the first study reporting the overexpression of STAT1 in human clear cell and papillary RCC tissues. Radiosensitization in RCC cell lines was observed by a reduction or inhibition of STAT1 signaling, using fludarabine or siRNA. Our data suggest that STAT1 may play a key role in RCC radioresistance and manipulation of this pathway may enhance the efficacy of radiotherapy.

  7. The preliminary SOL (Sizing and Optimization Language) reference manual

    NASA Technical Reports Server (NTRS)

    Lucas, Stephen H.; Scotti, Stephen J.

    1989-01-01

    The Sizing and Optimization Language, SOL, a high-level special-purpose computer language has been developed to expedite application of numerical optimization to design problems and to make the process less error-prone. This document is a reference manual for those wishing to write SOL programs. SOL is presently available for DEC VAX/VMS systems. A SOL package is available which includes the SOL compiler and runtime library routines. An overview of SOL appears in NASA TM 100565.

  8. Mast cell homeostasis and the JAK–STAT pathway

    PubMed Central

    Morales, JK; Falanga, YT; Depcrynski, A; Fernando, J; Ryan, JJ

    2011-01-01

    The Janus kinase/signal transducer and activator of transcription (JAK–STAT) pathway mediates important responses in immune cells. Activation of any of the four JAK family members leads to phosphorylation of one or more of seven STAT family members. Phosphorylation of STAT family members leads to their dimerization and translocation into the nucleus, in which they bind specific DNA sequences to activate gene transcription. Regulation of JAKs and STATs therefore has a significant effect on signal transduction and subsequent cellular responses. Mast cells are important mediators of allergic disease and asthma. These cells have the ability to cause profound inflammation and vasodilation upon the release of preformed mediators, as well as subsequent synthesis of new inflammatory mediators. The regulation of mast cells is therefore of intense interest for the treatment of allergic disease. An important regulator of mast cells, STAT5, is activated downstream of the receptors for immunoglobulin E, interleukin-3 and stem cell factor. STAT5 contributes to mast cell homeostasis, by mediating proliferation, survival, and mediator release. Regulators of the JAK–STAT pathway, such as the suppressors of cytokine signaling (SOCS) and protein inhibitor of activated STAT (PIAS) proteins, are required to fine tune the immune response and maintain homeostasis. A better understanding of the role and regulation of JAKs and STATs in mast cells is vital for the development of new therapeutics. PMID:20535135

  9. Inhibition of STAT3 by Anticancer Drug Bendamustine

    PubMed Central

    Iwamoto, Kazunori; Uehara, Yutaka; Inoue, Yukie; Taguchi, Kyoko; Muraoka, Daisuke; Ogo, Naohisa; Matsuno, Kenji; Asai, Akira

    2017-01-01

    Bendamustine (BENDA), which bears the bis(2-chloroethyl)amino moiety, is an alkylating agent that stops the growth of cancer cells by binding to DNA and interfering with its replication. However, the mechanism of action underlying its excellent clinical efficacy remains unclear. In this work, we report that BENDA inhibits signal transducer and activator of transcription 3 (STAT3). In an AlphaScreen-based biochemical assay using recombinant human STAT3, binding of STAT3–Src homology 2 (SH2) to the phosphotyrosine (pTyr, pY) peptide was inhibited by BENDA but not by the inactive metabolite dihydroxy bendamustine (HP2). When a single point mutation of C550A or C712A was introduced into recombinant human STAT3, its sensitivity to BENDA was substantially reduced, suggesting that these cysteine residues are important for BENDA to inhibit STAT3. Furthermore, BENDA suppressed the function of cellular STAT3 as a transcriptional activator in a human breast cancer cell line, MDA-MB-468, with constitutively activated STAT3. A competitive pull-down assay using biotinylated BENDA (Bio-BENDA) revealed that BENDA bound tightly to cellular STAT3, presumably through covalent bonds. Therefore, our results suggest that the anticancer effects of BENDA may be associated, at least in part, with its inhibitory effect on the SH2 domain of STAT3. PMID:28125678

  10. Sol-gel composite material characteristics caused by different dielectric constant sol-gel phases

    NASA Astrophysics Data System (ADS)

    Kimoto, Keisuke; Matsumoto, Makoto; Kaneko, Tsukasa; Kobayashi, Makiko

    2016-07-01

    Ultrasonic transducers prepared by a sol-gel composite method have been investigated in the field of nondestructive testing (NDT). Sol-gel composite materials could be ideal piezoelectric materials for ultrasonic transducer applications in the NDT field, and a new sol-gel composite with desirable characteristics has been developed. Three kinds of sol-gel composite materials composed of different dielectric constant sol-gel phases, Pb(Zr,Ti)O3 (PZT), Bi4Ti3O12 (BiT), and BaTiO3 (BT), and the same piezoelectric powder phase, PbTiO3 (PT), were fabricated and their properties were compared quantitatively. As a result, the PT/BT, sol-gel composite with the highest dielectric constant sol-gel phase showed the highest d 33 and signal strength. In addition, only PT/BT was successfully poled by room-temperature corona poling with reasonable signal strength.

  11. Addendum and Erratum: Nature of vibrational excitations in vitreous silica [Phys. Rev. B 56, 8605 (1997)

    NASA Astrophysics Data System (ADS)

    Shcheblanov, Nikita S.; Povarnitsyn, Mikhail E.; Taraskin, Sergei N.; Elliott, Stephen R.

    2016-09-01

    The aim of this paper is to clarify details of the projectional analysis for atomic vibrations in vitreous silica presented in a paper by Taraskin and Elliott [Phys. Rev. B 56, 8605 (1997), 10.1103/PhysRevB.56.8605]. The description of the stretching and bending modes has been discussed in detail while a description of the rotational modes and the procedure of their calculation have not been given in full detail. We specify the method for calculating the rotational modes omitted in the paper. We also correct a misprint in the expression for the B2(E ) mode which, unfortunately, has been reproduced in the vibrational analysis of the E mode in some publications.

  12. Chemistry Teacher Education Coalition: Extending the PhysTEC Model to Chemistry

    NASA Astrophysics Data System (ADS)

    Kirchhoff, Mary

    2012-02-01

    The American Association of Employment in Education reports that chemistry, like physics, faces ``some shortage'' of educators. Inspired by the success of the Physics Teacher Education Coalition (PhysTEC), the American Chemical Society (ACS) is developing the Chemistry Teacher Education Coalition (CTEC) to actively engage chemistry departments in the preparation of future chemistry teachers. Engaging chemistry departments in teacher preparation would increase the number and diversity of well-prepared high school chemistry teachers while catalyzing cultural change within chemistry departments. Many features of PhysTEC, such as a grant competition to create model teacher preparation programs and regular conferences, are directly applicable to chemistry. This presentation will provide an overview of ACS efforts to launch a successful CTEC initiative.

  13. Improving Science Teacher Preparation through the APS PhysTEC and NSF Noyce Programs

    NASA Astrophysics Data System (ADS)

    Williams, Tasha; Tyler, Micheal; van Duzor, Andrea; Sabella, Mel

    2013-03-01

    Central to the recruitment of students into science teaching at a school like CSU, is a focus on the professional nature of teaching. The purpose of this focus is twofold: it serves to change student perceptions about teaching and it prepares students to become teachers who value continued professional development and value the science education research literature. The Noyce and PhysTEC programs at CSU place the professional nature of teaching front and center by involving students in education research projects, paid internships, attendance at conferences, and participation in a new Teacher Immersion Institute and a Science Education Journal Reading Class. This poster will focus on specific components of our teacher preparation program that were developed through these two programs. In addition we will describe how these new components provide students with diverse experiences in the teaching of science to students in the urban school district. Supported by the NSF Noyce Program (0833251) and the APS PhysTEC Program.

  14. Permanent Habitats in Earth-Sol/Mars-Sol Orbit Positions

    NASA Astrophysics Data System (ADS)

    Greenspon, J.

    Project Outpost is a manned Earth-Sol/Mars-Sol platform that enables permanent occupation in deep space. In order to develop the program elements for this complex mission, Project Outpost will rely primarily on existing/nearterm technology and hardware for the construction of its components. For the purposes of this study, four mission requirements are considered: 1. Outpost - Man's 1st purpose-produced effort of space engineering, in which astructure is developed/constructed in an environment completely alien to currentpractices for EVA guidelines. 2. Newton - a concept study developed at StarGate Research, for the development ofa modified Hohmann personnel orbital transport operating between Earth andMars. Newton would serve as the primary crew delivery apparatus throughrepeatable transfer scheduling for all Earth-Lpoint-Mars activities. Thispermanent "transit system" would establish the foundations for Solar systemcolonization. 3. Cruis - a concept study developed at StarGate Research, for the development of amodified Hohmann cargo orbital transport operating between Earth and Mars.Cruis would serve as the primary equipment delivery apparatus throughrepeatable transfer scheduling for all Earth-Lpoint-Mars activities. Thispermanent "transit system" would establish the foundations for Solar systemcolonization, and 4. Ares/Diana - a more conventional space platform configuration for Lunar andMars orbit is included as a construction baseline. The operations of these assetsare supported, and used for the support, of the outpost. Outpost would be constructed over a 27-year period of launch opportunities into Earth-Sol or Mars-Sol Lagrange orbit (E-S/M-S L1, 4 or 5). The outpost consists of an operations core with a self-contained power generation ability, a docking and maintenance structure, a Scientific Research complex and a Habitation Section. After achieving initial activation, the core will provide the support and energy required to operate the outpost in a 365

  15. Comment on Weakly dissipative dust-ion acoustic wave modulation (J. Plasma Phys. 82, 905820104, 2016)

    NASA Astrophysics Data System (ADS)

    Kourakis, I.; Elkamash, I. S.

    2016-10-01

    In a recent article (J. Plasma Phys., vol. 82, 2009, 905820104), weakly dissipative dust-ion acoustic wave modulation in dusty plasmas was considered. It is shown in this Comment that the analysis therein involved severe fallacies, and is in fact based on an erroneous plasma fluid model, which fails to satisfy an equilibrium condition, among other shortcomings. The subsequent analysis therefore is dubious and of limited scientific value.

  16. Comment on "The universal instability in general geometry" [Phys. Plasmas 22, 090706 (2015)

    NASA Astrophysics Data System (ADS)

    Smolyakov, A. I.; Yagi, M.; Kishimoto, Y.

    2016-11-01

    It is pointed out that the destabilization mechanism recently discussed by Helander and Plunk in relation to the universal instability was studied previously by Smolyakov et al. [Phys. Rev. Lett. 89, 125005 (2002)]. Moreover, the contribution of the trapped particles as discussed by Helander and Plunk is closely related to the mechanism of the ubiquitous instability previously studied by Coppi and Pegoraro [Nucl. Fusion 17, 969 (1977)].

  17. Comment on ``Multireference configuration-interaction calculations for positronium halides'' [J. Chem. Phys. 122, 054302 (2005)

    NASA Astrophysics Data System (ADS)

    Mitroy, J.; Bromley, M. W. J.

    2005-07-01

    Large-scale configuration-interaction calculations of the binding energies and annihilation rates of the positronium halides, PsF, PsCl, PsBr, and PsI [S. L. Saito, J. Chem. Phys. 122 054302 (2005)], have made erroneous predictions about the structures of these atoms. The predictions were based on small annihilation rates, which result from using a small basis and additionally invalid estimates of the contributions from single-particle orbitals with ℓ >8 .

  18. The non-pathogenic Henipavirus Cedar paramyxovirus phosphoprotein has a compromised ability to target STAT1 and STAT2.

    PubMed

    Lieu, Kim G; Marsh, Glenn A; Wang, Lin-Fa; Netter, Hans J

    2015-12-01

    Immune evasion by the lethal henipaviruses, Hendra (HeV) and Nipah virus, is mediated by its interferon (IFN) antagonist P gene products, phosphoprotein (P), and the related V and W proteins, which can target the signal transducer and activator of transcription 1 (STAT1) and STAT2 proteins to inhibit IFN/STAT signaling. However, it is not clear if the recently identified non-pathogenic Henipavirus, Cedar paramyxovirus (CedPV), is also able to antagonize the STAT proteins. We performed comparative studies between the HeV P gene products (P/V/W) and CedPV-P (CedPV does not encode V or W) and demonstrate that differences exist in their ability to engage the STAT proteins using immunoprecipitation and quantitative confocal microscopic analysis. In contrast to HeV-P gene encoded proteins, the ability of CedPV-P to interact with and relocalize STAT1 or STAT2 is compromised, correlating with a reduced capacity to inhibit the mRNA synthesis of IFN-inducible gene MxA. Furthermore, infection studies with HeV and CedPV demonstrate that HeV is more potent than CedPV in inhibiting the IFN-α-mediated nuclear accumulation of STAT1. These results strongly suggest that the ability of CedPV to counteract the IFN/STAT response is compromised compared to HeV.

  19. Activation of Hepatic STAT3 Maintains Pulmonary Defense during Endotoxemia

    PubMed Central

    Hilliard, Kristie L.; Allen, Eri; Traber, Katrina E.; Kim, Yuri; Wasserman, Gregory A.; Jones, Matthew R.; Mizgerd, Joseph P.

    2015-01-01

    Pneumonia and infection-induced sepsis are worldwide public health concerns. Both pathologies elicit systemic inflammation and induce a robust acute-phase response (APR). Although APR activation is well regarded as a hallmark of infection, the direct contributions of liver activation to pulmonary defense during sepsis remain unclear. By targeting STAT3-dependent acute-phase changes in the liver, we evaluated the role of liver STAT3 activity in promoting host defense in the context of sepsis and pneumonia. We employed a two-hit endotoxemia/pneumonia model, whereby administration of 18 h of intraperitoneal lipopolysaccharide (LPS; 5 mg/kg of body weight) was followed by intratracheal Escherichia coli (106 CFU) in wild-type mice or those lacking hepatocyte STAT3 (hepSTAT3−/−). Pneumonia alone (without endotoxemia) was effectively controlled in the absence of liver STAT3. Following endotoxemia and pneumonia, however, hepSTAT3−/− mice, with significantly reduced levels of circulating and airspace acute-phase proteins, exhibited significantly elevated lung and blood bacterial burdens and mortality. These data suggested that STAT3-dependent liver responses are necessary to promote host defense. While neither recruited airspace neutrophils nor lung injury was altered in endotoxemic hepSTAT3−/− mice, alveolar macrophage reactive oxygen species generation was significantly decreased. Additionally, bronchoalveolar lavage fluid from this group of hepSTAT3−/− mice allowed greater bacterial growth ex vivo. These results suggest that hepatic STAT3 activation promotes both cellular and humoral lung defenses. Taken together, induction of liver STAT3-dependent gene expression programs is essential to countering the deleterious consequences of sepsis on pneumonia susceptibility. PMID:26216424

  20. Opportunity's View on Sol 354

    NASA Technical Reports Server (NTRS)

    2005-01-01

    NASA's Mars Exploration Rover Opportunity captured this 360-degree panorama with its navigation camera on the rover's 354th martian day, or sol (Jan. 21, 2005). The view is presented as a cylindrical projection with geometric seam correction. Just to the right of center is the divot where Opportunity's heat shield hit the ground after protecting the spacecraft during descent through Mars'atmosphere. The heat shield was jettisoned about 90 seconds before Opportunity landed about 800 meters (half a mile) away. To the left of the divot is the flank portion of the heat shield debris and in the left foreground is the main wreckage of the heat shield. On the far right is a basketball-size rock dubbed 'Heat Shield Rock,' which Opportunity's inspection identified as an iron-nickel meteorite. The rim of 'Endurance Crater' is visible on the horizon on both the left and right ends of this full-circle view.

  1. β-Arrestin 1’s Interaction with TC45 Attenuates Stat signaling by dephosphorylating Stat to inhibit antimicrobial peptide expression

    PubMed Central

    Sun, Jie-Jie; Yang, Hui-Ting; Niu, Guo-Juan; Feng, Xiao-Wu; Lan, Jiang-Feng; Zhao, Xiao-Fan; Wang, Jin-Xing

    2016-01-01

    Impaired phosphatase activity leads to the persistent activation of signal transducers and activators of transcription (Stat). In mammals, Stat family members are often phosphorylated or dephosphorylated by the same enzymes. To date, only one Stat similar to mammalian Stat5a/b has been found in crustaceans and there have been few studies in Stat signal regulation in crustaceans. Here, we report that β-arrestin1 interacts with TC45 (45-kDa form of T cell protein tyrosine phosphatase) in the nucleus to attenuate Stat signaling by promoting dephosphorylation of Stat. Initially, we showed that Stat translocates into the nucleus to induce antimicrobial peptide (AMP) expression after bacterial infection. βArr1 enters the nucleus of hemocytes and recruits TC45 to form the βarr1-TC45-Stat complex, which dephosphorylates Stat efficiently. The interaction of TC45 with Stat decreased and Stat phosphorylation increased in βarr1-silenced shrimp (Marsupenaeus japonicus) after challenge with Vibrio anguillarum. βArr1 directly interacts with Stat in nucleus and accelerates Stat dephosphorylation by recruiting TC45 after V. anguillarum challenge. Further study showed that βarr1 and TC45 also affect AMP expression, which is regulated by Stat. Therefore, βarr1 and TC45 are involved in the anti-V. anguillarum immune response by regulating Stat activity negatively to decrease AMP expression in shrimp. PMID:27782165

  2. Combinatorial methods in sol-gel technology

    NASA Astrophysics Data System (ADS)

    Rantala, Juha T.; Kololuoma, Terho K.; Kivimaki, L.

    2000-05-01

    Sol-gel processing consists several variable parameters during materials synthesis and post processing steps. The sol-gel synthesis is rather sensitive for the parameters such as pH, temperature, type of catalyst, reaction time etc. However, this sensitivity can be taken as an advantage when developing and studying new materials and their properties. Furthermore, since the sol-gel technology mainly describes the fabrication of solid state materials from a liquid phase by applying metal alkoxides or metal salts as precursors, the post processing such as sintering has critical effects on the final form and properties of the solid material. Combinatorial chemistry and methods are valuable tools to estimate the effects of different variables and to build-up combinatorial libraries for the sol-gel technique. This paper generally describes potentials and the usage motivation of combinatorial chemistry in the sol-gel technology by taking into account some major steps in the synthesis and processing which are valuable for the estimation of the final product properties. Different kind of post processing steps in the combinatorial manner are studied in details. As an example the post processing of sol-gel derived semiconductor oxides and photosensitivity of hybrid sol-gel glasses are presented. The combinatorial treatment and measurement methods for these materials are explained.

  3. 7th International Conference on Excitonic Processes in Condensed Matter (EXCON'06) Winston-Salem, NC, USA, 26-30 June 2006

    NASA Astrophysics Data System (ADS)

    Petelenz, P.; Schreiber, M.

    2006-10-01

    This conference report is meant to offer an authoritative view on a recently held scientific meeting rather than a comprehensive list of the conference presentations. We tried to describe what we feel were the most interesting contributions.The full Proceedings of the 7th International Conference on Excitonic Processes in Condensed Matter (EXCON'06) shall be published in phys. stat. sol. (b) and phys. stat. sol. (c) in November 2006.

  4. Policy on Counting Superseded Checklists in StATS

    EPA Pesticide Factsheets

    As we proceed with implementing the State Authorization Tracking System (StATS), and develop management reports based on data in StATS, we continue to identify issues dealing with what events should or should not be counted in the system.

  5. STAT5 and CD4 + T Cell Immunity

    PubMed Central

    Owen, David L.; Farrar, Michael A.

    2017-01-01

    STAT5 plays a critical role in the development and function of many cell types. Here, we review the role of STAT5 in the development of T lymphocytes in the thymus and its subsequent role in the differentiation of distinct CD4 + helper and regulatory T-cell subsets. PMID:28163905

  6. Paradigm shifts in the cell biology of STAT signaling

    PubMed Central

    2008-01-01

    In recent years several of the key tenets of the original cytokine-STAT signaling paradigm have had to be revised. First, that nonphosphorylated “inactive” STATs are present in the cytoplasm as free monomers which dimerized only subsequent to Tyr-phosphorylation has been replaced by the understanding that nonphosphorylated STATs in the cytoplasm exist largely as dimers and high molecular mass “statosome” complexes. Second, the notion that phosphorylation, either of Tyr or Ser residues or both, in STAT species is required for transcriptional activation has been replaced by the realization that nonphosphorylated STATs can be transcriptionally active albeit with respect to sets of target genes distinct from phosphorylated STATs. Third, the notion that it is the activation by phosphorylation of STATs at the plasma membrane that then leads to their import into the nucleus has been replaced by the recognition that even nonphosphorylated STATs shuttle between the cytoplasm and nucleus at all times in a constitutive manner. Fourth, the notion that the trans-cytoplasmic transit of STATs from the plasma membrane to the nuclear import machinery takes place exclusively as a free cytosolic process has been replaced by the understanding that at least a portion of this trans-cytoplasmic transit is mediated via membrane-associated caveolar and endocytic trafficking (the “signaling endosome” hypothesis). Fifth, the targeting and sequestration of activated STAT3 to long-lived endosomes in the cytoplasm requires consideration of STAT3-mediated “signal transduction” from the plasma membrane to cytoplasmic membrane destinations potentially for function(s) in the cytoplasm. Indeed, in tissue sections many discrete histologic cell types display PY-STAT3 almost exclusively in the cytoplasm with little, if any, in the nucleus. New challenges include determining the structural bases for the recruitment of nonphosphorylated dimeric STAT species to the cytosolic face of

  7. Role of STAT3 pathway in genitourinary tumors

    PubMed Central

    Santoni, Matteo; Conti, Alessandro; Piva, Francesco; Massari, Francesco; Ciccarese, Chiara; Burattini, Luciano; Cheng, Liang; Lopez-Beltran, Antonio; Scarpelli, Marina; Santini, Daniele; Tortora, Giampaolo; Cascinu, Stefano; Montironi, Rodolfo

    2015-01-01

    The STAT3 is often dysregulated in genitourinary tumors. In prostate cancer, STAT3 activation correlates with Gleason score and pathological stage and modulates cancer stem cells and epithelial–mesenchymal transition. In addition, STAT3 promotes the progression from carcinoma in situ to invasive bladder cancer and modulates renal cell carcinoma angiogenesis by increasing the expression of HIF1α and VEGF. STAT3 is also involved in the response to tyrosine kinase inhibitors sunitinib and axitinib, in patients with metastatic renal cell carcinoma, and to second-generation androgen receptor inhibitor enzalutamide in patients with advanced prostate cancer. In this review, we describe the role of STAT3 in genitourinary tumors, thus describing its potential for future therapeutic strategies. PMID:28031890

  8. Propulsion Study for Small Transport Aircraft Technology (STAT)

    NASA Technical Reports Server (NTRS)

    Gill, J. C.; Earle, R. V.; Staton, D. V.; Stolp, P. C.; Huelster, D. S.; Zolezzi, B. A.

    1980-01-01

    Propulsion requirements were determined for 0.5 and 0.7 Mach aircraft. Sensitivity studies were conducted on both these aircraft to determine parametrically the influence of propulsion characteristics on aircraft size and direct operating cost (DOC). Candidate technology elements and design features were identified and parametric studies conducted to select the STAT advanced engine cycle. Trade off studies were conducted to determine those advanced technologies and design features that would offer a reduction in DOC for operation of the STAT engines. These features were incorporated in the two STAT engines. A benefit assessment was conducted comparing the STAT engines to current technology engines of the same power and to 1985 derivatives of the current technology engines. Research and development programs were recommended as part of an overall technology development plan to ensure that full commercial development of the STAT engines could be initiated in 1988.

  9. STAT6: its role in interleukin 4-mediated biological functions.

    PubMed

    Takeda, K; Kishimoto, T; Akira, S

    1997-05-01

    Interleukin (IL) 4 is known to be a cytokine which plays a central role in the regulation of immune response. Studies on cytokine signal transduction have clarified the mechanism by which IL4 exerts its functions. Two cytoplasmic proteins, signal transducer and activator of transcription (STAT) 6 and IL4-induced phosphotyrosine substrate/insulin receptor substrate 2 (4PS/IRS2), are activated in IL4 signal transduction. Recent studies from STAT6-deficient mice have revealed the essential role of STAT6 in IL4-mediated biological actions. In addition, STAT6 has also been demonstrated to be important for the functions mediated by IL13, which is related to IL4. IL4 and IL13 have been shown to induce the production of IgE, which is a major mediator in an allergic response. These findings indicate that STAT6 activation is involved in IL4- and IL13-mediated disorders such as allergy.

  10. Using the PhysX engine for Physics-based Virtual Surgery with Force Feedback

    PubMed Central

    Maciel, Anderson; Halic, Tansel; Lu, Zhonghua; Nedel, Luciana P.; De, Suvranu

    2010-01-01

    Background The development of modern surgical simulators is highly challenging as they must support complex simulation environments. The demand for higher realism in such simulators has driven researchers to adopt physics-based models which are computationally very demanding. This poses a major problem since real time interactions must permit graphical updates of 30 Hz and a much higher rate of 1 kHz for force feedback (haptics). Recently several physics engines have been developed which offer multi-physics simulation capabilities including rigid and deformable bodies, cloth and fluids. While such physics engines provide unique opportunities for the development of surgical simulators, their higher latencies, compared to what is necessary for real time graphics and haptics, offer significant barriers to their use in interactive simulation environments. Methods In this work, we propose solutions to this problem and demonstrate how a multimodal surgical simulation environment may be developed based on NVIDIA’s PhysX physics library. Hence, models that are undergoing relatively low frequency updates in PhysX can exist in an environment that demands much higher frequency updates for haptics. We use a collision handling layer to interface between the physical response provided by PhysX and the haptic rendering device to provide both real time tissue response and force feedback. Results Our simulator integrates a bimanual haptic interface for force-feedback and per-pixel shaders for graphics realism in real time. To demonstrate the effectiveness of our approach, we present the simulation of the Laparoscopic Adjustable Gastric Banding (LAGB) procedure as a case study. Conclusions To develop complex and realistic surgical trainers with realistic organ geometries and tissue properties demands stable physics-based deformation methods which are not always compatible with the interaction level required for such trainers. We have shown that combining different modeling

  11. Different STAT transcription complexes drive early and delayed responses to type I Interferons

    PubMed Central

    Plumlee, Courtney R.; Perry, Stuart; Gu, Ai Di; Lee, Carolyn; Shresta, Sujan; Decker, Thomas; Schindler, Christian

    2015-01-01

    Interferons, which transduce pivotal signals through signal transducer and activator of transcription (Stat)1 and Stat2, effectively suppress the replication of Legionella pneumophila in primary murine macrophages. Whereas the ability of IFN-γ to impede L. pneumophila growth is fully dependent on Stat1, IFN-α/β unexpectedly suppresses L. pneumophila growth in both Stat1 and Stat2 deficient macrophages. New studies demonstrating that the robust response to IFN-α/β is lost in Stat1-Stat2 double knockout macrophages, suggest that Stat1 and Stat2 are functionally redundant in their ability to direct an innate response towards L. pneumophila. Since the ability of IFN-α/β to signal through Stat1-dependent complexes (i.e., Stat1-Stat1 and Stat1-Stat2 dimers) has been well characterized, the current studies focus on how Stat2 is able to direct a potent response to IFN-α/β in the absence of Stat1. These studies reveal that IFN-α/β is able to drive the formation of a Stat2 and IRF9 complex that drives the expression of a subset of IFN stimulated genes (ISGs), but with substantially delayed kinetics. These observations raise the possibility that this pathway evolved in response to microbes that have devised strategies to subvert Stat1 dependent responses. PMID:26019270

  12. Comment on 'General nonlocality in quantum fields'[J. Math. Phys. 49, 033513 (2008)

    SciTech Connect

    Wang Haijun

    2010-05-15

    In a recent paper [H.-J. Wang, J. Math. Phys. 49, 033513 (2008)] a complex-geometry model was proposed to interpret the interaction of electromagnetism and the interaction between quarks while the nonlocal effects are involved. In that theoretical frame, from the metric matrix one can obtain a determinant-form condition to describe qualitatively the typical characteristics for the aforementioned interactions. In this comment we attempt to extend this kind of qualitative description to weak interaction by finding out an appropriate metric tensor for it.

  13. Comment on ``Quasirelativistic theory equivalent to fully relativistic theory'' [J. Chem. Phys. 123, 241102 (2005)

    NASA Astrophysics Data System (ADS)

    Filatov, Michael

    2006-09-01

    The connection between the exact quasirelativistic approach developed in the title reference [W. Kutzelnigg and W. Liu, J. Chem. Phys. 123, 241102 (2005)] and the method of elimination of the small component in matrix form developed previously by Dyall is explicitly worked out. An equation that links Hermitian and non-Hermitian formulations of the exact quasirelativistic theory is derived. Besides establishing a kinship between the existing formulations, the proposed equation can be employed for the derivation of new formulations of the exact quasirelativistic theory.

  14. Comment on 'Thermodynamic cycles and the calculation of p Ka' [Chem. Phys. Lett. 367 (2003) 145

    NASA Astrophysics Data System (ADS)

    da Silva, Clarissa O.; da Silva, Edilson C.; Nascimento, Marco A. C.

    2003-11-01

    In a recent Letter, Pliego [Chem. Phys. Lett. 367 (2003) 145] has raised some questions about the methodology that we have employed for calculating p Ka values in aqueous solutions. In this comment we show that the problem with Pliego's analysis is the fact that he used Ben-Naim's definition of Δ Gsol for both the solute and the solvent, which implies that the concentration, for both components, should be equal to 1 M. For the solute, this is a reference state fully compatible with the quantum description, but for the solvent this choice is unphysical, as discussed in the Letter.

  15. Sol-gel antireflective coating on plastics

    DOEpatents

    Ashley, Carol S.; Reed, Scott T.

    1990-01-01

    An antireflection film made from a reliquified sol-gel hydrolyzation, condensation polymeric reaction product of a silicon, alkoxides and/or metal alkoxides, or mixtures thereof. The film is particularly useful for coating plastics.

  16. Sol-gel antireflective coating on plastics

    DOEpatents

    Ashley, C.S.; Reed, S.T.

    1988-01-26

    An antireflection film made from reliquified sol-gel hydrolyzation, condensation polymeric reaction product of a silicon, alkoxides and/or metal alkoxides, or mixtures thereof. The film is particularly useful for coating plastics.

  17. Sol-gel deposited electrochromic coatings

    SciTech Connect

    Ozer, N.; Lampert, C.M.

    1995-06-01

    Electrochromic devices have increasing application in display devices, switchable mirrors and smart windows. A variety of vacuum deposition technologies have been used to make electrochromic devices. The sol- gel process offers an alternative approach to the synthesis of optical quality and low cost electrochromic device layers. This study summarizes the developments in sol-gel deposited electrochromic films. The sol-gel process involves the formation of oxide networks upon hydrolysis-condensation of alkoxide precursors. In this study we cover the sol-gel deposited oxides of WO[sub 3], V[sub 2]O[sub 5], TiO[sub 2], Nb[sub 2]O[sub 5], and NiO[sub x].

  18. 'Algonquin' Outcrop on Spirit's Sol 680

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This view combines four frames from Spirit's panoramic camera, looking in the drive direction on the rover's 680th Martian day, or sol (Dec. 1, 2005). The outcrop of apparently layered bedrock has the informal name 'Algonquin.'

  19. So, Why Sol-Mi? American Music Education

    ERIC Educational Resources Information Center

    Bennett, Peggy D.

    2005-01-01

    Walk into any primary grade music class in the U.S., and you will likely hear teacher and students singing a musical greeting, such as "Good morning boys and girls" (sol-mi-mi-sol-sol-mi) and the response "Good morning Miss Purdy" (sol-mi-mi-sol-mi-mi). Since about the 1970s, teachers have been beginning and ending music class for young children…

  20. Spirit 360-Degree View, Sol 388

    NASA Technical Reports Server (NTRS)

    2005-01-01

    NASA's Mars Exploration Rover Spirit used its navigation camera to take the images combined into this 360-degree view of the rover's surroundings on Spirit's 388th martian day, or sol (Feb. 4, 2005). Spirit had driven about 13 meters (43 feet) uphill toward 'Cumberland Ridge' on this sol. This location is catalogued as Spirit's Site 102, Position 513. The view is presented in a cylindrical projection with geometric and brightness seam correction.

  1. Spirit 360-Degree View, Sol 388 (polar)

    NASA Technical Reports Server (NTRS)

    2005-01-01

    NASA's Mars Exploration Rover Spirit used its navigation camera to take the images combined into this 360-degree view of the rover's surroundings on Spirit's 388th martian day, or sol (Feb. 4, 2005). Spirit had driven about 13 meters (43 feet) uphill toward 'Cumberland Ridge' on this sol. This location is catalogued as Spirit's Site 102, Position 513. The view is presented in a cylindrical projection with geometric and brightness seam correction.

  2. Spirit 360-Degree View, Sol 388 (vertical)

    NASA Technical Reports Server (NTRS)

    2005-01-01

    NASA's Mars Exploration Rover Spirit used its navigation camera to take the images combined into this 360-degree view of the rover's surroundings on Spirit's 388th martian day, or sol (Feb. 4, 2005). Spirit had driven about 13 meters (43 feet) uphill toward 'Cumberland Ridge' on this sol. This location is catalogued as Spirit's Site 102, Position 513. The view is presented in a vertical projection with geometric and brightness seam correction.

  3. The relationship between total and phosphorylated STAT1 and STAT3 tumour cell expression, components of tumour microenvironment and survival in patients with invasive ductal breast cancer

    PubMed Central

    Gujam, Fadia J.A.; McMillan, Donald C.; Edwards, Joanne

    2016-01-01

    The aim of the present study was to examine the relationship between tumour cell expression of total and phosphorylated STAT1 (ph-STAT1) and STAT3 (ph-STAT-3), components of tumour microenvironment and survival in patients with invasive ductal breast cancer. Immunohistochemical analysis of total and ph-STAT1, and STAT3 were performed on tissue microarray of 384 breast cancer specimens. Tumour cell expression of STAT1 and STAT3 at both cytoplasmic and nuclear locations were combined and identified as STAT1/STAT3 tumour cell expression. These results were related to cancer specific survival (CSS) and phenotypic features of the tumour and the host. High ph-STAT1 and ph-STAT3 tumour cell expression were associated with increased ER (both P≤0.001) and PR (both P <0.05), reduced tumour grade (P=0.015 and P<0.001 respectively) and necrosis (both P=0.001). Ph-STAT1 was associated with increased general inflammatory infiltrate (P=0.007) and ph-STAT3 was associated with lower CD4+ infiltration (P=0.024). In multivariate survival analysis, only high ph-STAT3 tumour cell expression was a predictor of improved CSS (P=0.010) independent of other tumour and host-based factors. STAT1 and STAT3 tumour cell expression appeared to be an important determinant of favourable outcome in patients with invasive ductal breast cancer. The present results suggest that STAT1 and STAT3 may affect disease outcome through direct impact on tumour cells, counteracting aggressive tumour features, as well as interaction with the surrounding microenvironment. PMID:27769057

  4. JAK/STAT/SOCS-signaling pathway and colon and rectal cancer

    PubMed Central

    Slattery, Martha L.; Lundgreen, Abbie; Kadlubar, Susan A.; Bondurant, Kristina L.; Wolff, Roger K.

    2012-01-01

    The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is involved in immune function and cell growth. We evaluated the association between genetic variation in JAK1 (10 SNPs), JAK2 (9 SNPs), TYK2 (5 SNPs), SOCS1 (2 SNPs), SOCS2 (2 SNPs), STAT1 (16 SNPs), STAT2 (2 SNPs), STAT3 (6 SNPs), STAT4 (21 SNPs), STAT5A (2 SNPs), STAT5B (3 SNPs), STAT6 (4 SNPs) with risk of colorectal cancer. We used data from population-based case-control studies (colon cancer n=1555 cases, 1956 controls; rectal cancer n=754 cases, 959 controls). JAK2, SOCS2, STAT1, STAT3, STAT5A, STAT5B, and STAT6 were associated with colon cancer; STAT3, STAT4, STAT6, and TYK2 were associated with rectal cancer. Given the biological role of the JAK/STAT-signaling pathway and cytokines, we evaluated interaction with IFNG, TNF, and IL6; numerous statistically significant associations after adjustment for multiple comparisons were observed. The following statistically significant interactions were observed: TYK2 with aspirin/NSAID use; STAT1, STAT4, and TYK2 with estrogen status; and JAK2, STAT2, STAT4, STAT5A, STAT5B, and STAT6 with smoking status and colon cancer risk; JAK2, STAT6, and TYK2 with aspirin/NSAID use; JAK1 with estrogen status; STAT2 with cigarette smoking and rectal cancer. JAK2, SOCS1, STAT3, STAT5, and TYK2 were associated with colon cancer survival (HRR of 3.3 95% CI 2.01, 5.42 for high mutational load). JAK2, SOCS1, STAT1, STAT4, and TYK2 were associated with rectal cancer survival (HRR 2.80 95 %CI 1.63, 4.80). These data support the importance of the JAK/STAT-signaling pathway in colorectal cancer and suggest targets for intervention. PMID:22121102

  5. Sol-gel method for encapsulating molecules

    DOEpatents

    Brinker, C. Jeffrey; Ashley, Carol S.; Bhatia, Rimple; Singh, Anup K.

    2002-01-01

    A method for encapsulating organic molecules, and in particular, biomolecules using sol-gel chemistry. A silica sol is prepared from an aqueous alkali metal silicate solution, such as a mixture of silicon dioxide and sodium or potassium oxide in water. The pH is adjusted to a suitably low value to stabilize the sol by minimizing the rate of siloxane condensation, thereby allowing storage stability of the sol prior to gelation. The organic molecules, generally in solution, is then added with the organic molecules being encapsulated in the sol matrix. After aging, either a thin film can be prepared or a gel can be formed with the encapsulated molecules. Depending upon the acid used, pH, and other processing conditions, the gelation time can be from one minute up to several days. In the method of the present invention, no alcohols are generated as by-products during the sol-gel and encapsulation steps. The organic molecules can be added at any desired pH value, where the pH value is generally chosen to achieve the desired reactivity of the organic molecules. The method of the present invention thereby presents a sufficiently mild encapsulation method to retain a significant portion of the activity of the biomolecules, compared with the activity of the biomolecules in free solution.

  6. STAT1 drives tumor progression in serous papillary endometrial cancer.

    PubMed

    Kharma, Budiman; Baba, Tsukasa; Matsumura, Noriomi; Kang, Hyun Sook; Hamanishi, Junzo; Murakami, Ryusuke; McConechy, Melissa M; Leung, Samuel; Yamaguchi, Ken; Hosoe, Yuko; Yoshioka, Yumiko; Murphy, Susan K; Mandai, Masaki; Hunstman, David G; Konishi, Ikuo

    2014-11-15

    Recent studies of the interferon-induced transcription factor STAT1 have associated its dysregulation with poor prognosis in some cancers, but its mechanistic contributions are not well defined. In this study, we report that the STAT1 pathway is constitutively upregulated in type II endometrial cancers. STAT1 pathway alteration was especially prominent in serous papillary endometrial cancers (SPEC) that are refractive to therapy. Our results defined a "SPEC signature" as a molecular definition of its malignant features and poor prognosis. Specifically, we found that STAT1 regulated MYC as well as ICAM1, PD-L1, and SMAD7, as well as the capacity for proliferation, adhesion, migration, invasion, and in vivo tumorigenecity in cells with a high SPEC signature. Together, our results define STAT1 as a driver oncogene in SPEC that modulates disease progression. We propose that STAT1 functions as a prosurvival gene in SPEC, in a manner important to tumor progression, and that STAT1 may be a novel target for molecular therapy in this disease.

  7. STAT4 gene polymorphism in patients after renal allograft transplantation

    PubMed Central

    Dąbrowska-Żamojcin, Ewa; Dziedziejko, Violetta; Safranow, Krzysztof; Domański, Leszek; Słuczanowska-Głabowska, Sylwia

    2016-01-01

    Introduction STAT4 (signal transducer and activator of transcription 4) is involved in the regulation of innate and adaptive immune responses. Some studies have suggested that STAT4 may be involved in the immune response after graft transplantation. Several polymorphisms in the STAT4 gene have been identified. The most commonly studied polymorphism in the STAT4 gene is rs7574865. In our study, we examined whether this polymorphism is associated with the early and late functions of renal allografts. Material and methods A total of 270 recipients of first renal transplants were included in the study. Single nucleotide polymorphisms (SNPs) within the STAT4 gene were genotyped using TaqMan genotyping assays. Results There were no statistically significant associations between the STAT4 gene rs7574865 polymorphism and delayed graft function, acute rejection, chronic allograft dysfunction, post-transplant diabetes mellitus, or creatinine serum concentrations after transplantation. Conclusions Our results suggest a lack of association between the STAT4 rs7574865 SNP and kidney allograft function in the Polish population. PMID:27833442

  8. Idiopathic pancreatitis in a patient with a STAT3 mutation

    PubMed Central

    Peppers, Brian; Frith, John; Tcheurekdjian, Haig; Hostoffer, Robert

    2016-01-01

    Background: Hyperimmunoglobulin E syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent skin infections with abscesses, recurrent pneumonias with pneumatoceles, and immunoglobulin E levels of >10 times the upper limit of normal. Case: The patient described herein had a classic case of signal transducer and activator of transcription 3 (STAT3) deficiency associated with HIES diagnosed several years before this particular presentation. He demonstrated extraimmune manifestations of the disease as well, including characteristic facies and a history of skeletal fractures. In addition, the patient had several distinct episodes of idiopathic pancreatitis for which a full gastrointestinal workup had been performed. STAT3 mutation was confirmed by genotyping at the time of diagnosis of HIES. Conclusions: STAT3, a mammalian protein that regulates cell growth, survival, and differentiation, has been linked to human pancreatic carcinogenesis as well as the above-mentioned immune deficiency. Mouse studies demonstrated that genetic ablation of STAT3 exacerbates the course of acute pancreatitis, whereas normal pancreatic STAT3 seems to have a protective effect against necrotizing pancreatitis. An association between STAT3 mutations and pancreatitis has not yet been revealed in humans. Here we describe a case of acute pancreatitis that presented in a patient with STAT3 mutation. PMID:27103560

  9. STAT signaling in the pathogenesis and treatment of cancer.

    PubMed Central

    Frank, D. A.

    1999-01-01

    Exceptional advances have been made recently in our understanding of the signaling pathways that control cellular growth, differentiation, and survival. These processes are regulated by extracellular stimuli such as cytokines, cell-cell interactions, and cell-matrix interactions, which trigger a series of intracellular events culminating in the modulation of specific genes. STATs are a highly homologous group of transcription factors that are activated by various pathways and regulate many of the genes controlling cellular function. STATs are activated by tyrosine phosphorylation and modulated by serine phosphorylation, placing them at a convergence point for numerous intracellular signaling pathways. Given the importance of STATs in the control of normal physiologic processes, it is not surprising that inappropriate activation of these proteins has been found in human malignancies. A number of distinct mechanisms have been elucidated by which STATs are activated inappropriately, including autocrine or paracrine stimulation of normal receptors and increased activity of tyrosine kinases through enhanced expression, mutations, or the presence of activating proteins. Furthermore, inappropriate STAT serine phosphorylation has been found in several tumors as well. The increased understanding of signaling pathways in tumors can be translated into therapeutic strategies that have the potential to be more selective and less toxic than current anti-cancer treatments. Approaches which may be effective include the development of antagonists of receptors that can trigger STAT activation, inhibitors of the tyrosine and serine kinases that phosphorylate and activate STATs, agents that decrease STAT levels or inhibit their recruitment to kinases, and molecules that can prevent the binding of STATs to target DNA sequences. Thus, elucidation of cellular and biochemical processes in tumors has enhanced our understanding of the pathogenesis of malignancies and may provide the basis

  10. Comment on "Diffusion by a random velocity field" [Phys. Fluids 13, 22 (1970)

    NASA Astrophysics Data System (ADS)

    Saad, Tony; Sutherland, James C.

    2016-11-01

    This comment aims at addressing a mass conservation issue in a paper published in the physics of fluids. The paper [R. H. Kraichnan, "Diffusion by a random velocity field," Phys. Fluids 13(1), 22 (1970)] introduces a novel method to generate synthetic isotropic turbulence for computational purposes. The method has been used in the literature to generate inlet boundary conditions and to model aeroacoustic noise as well as for validation and verification purposes. However, the technique uses a continuous formulation to derive the mass conservation constraint. In this comment, we argue that the continuous constraint is invalid on a discrete grid and provide an alternative derivation using the discrete divergence. In addition, we present an analysis to quantify the impact of a pressure projection on the kinetic energy of a non-solenoidal velocity field.

  11. Comment on ``Global thermodynamics of hydrophobic cavitation, dewetting, and hydration'' [J. Chem. Phys. 123, 184504 (2005)

    NASA Astrophysics Data System (ADS)

    Graziano, Giuseppe

    2006-07-01

    It is pointed out that in a Ben-Amotz in a recent article [J. Chem. Phys.123, 184504 (2005)] attributed a noncorrect meaning to the entropy convergence temperature, claiming that the latter corresponds to the temperature at which the hydration entropy of a series of solutes crosses zero. A short resumé of the entropy convergence phenomenon and of the provided statistical mechanical analyses is accomplished. In addition, it is brought out that the different temperature dependence of the cavity entropy change on increasing the cavity diameter, pointed out by Ben-Amotz, originates from the assumption that the work of cavity creation should be proportional to the experimental surface tension of liquid water for cavities large on a molecular scale.

  12. Complex roles of Stat1 in regulating gene expression.

    PubMed

    Ramana, C V; Chatterjee-Kishore, M; Nguyen, H; Stark, G R

    2000-05-15

    Stat1 is a fascinating and complex protein with multiple, yet contrasting transcriptional functions. Upon activation, it drives the expression of many genes but also suppresses the transcription of others. These opposing characteristics also apply to its role in facilitating crosstalk between signal transduction pathways, as it participates in both synergistic activation and inhibition of gene expression. Stat1 is a functional transcription factor even in the absence of inducer-mediated activation, participating in the constitutive expression of some genes. This review summarizes the well studied involvement of Stat1 in IFN-dependent and growth factor-dependent signaling and then describes the roles of Stat1 in positive, negative and constitutive regulation of gene expression as well as its participation in crosstalk between signal transduction pathways. Oncogene (2000).

  13. Comment on “Effects of damping solitary wave in a viscosity bounded plasma” [Phys. Plasmas 21, 022118 (2014)

    SciTech Connect

    Ghosh, Uday Narayan Chatterjee, Prasanta; Roychoudhury, Rajkumar

    2015-07-15

    Recently Gun Li et al. discussed “Effects of damping solitary wave in a viscosity bounded plasma” [Phys. Plasmas 21, 022118 (2014)]. The paper contains some serious errors which have been pointed out in this Comment.

  14. Development of T-STAT for Early Autism Screening

    ERIC Educational Resources Information Center

    Chiang, Chung-Hsin; Wu, Chin-Chin; Hou, Yuh-Ming; Chu, Ching-Lin; Liu, Jiun-Horng; Soong, Wei-Tsuen

    2013-01-01

    This study's purpose was to modify the Screening Tool for Autism in Two-Year-Olds (STAT) into a Taiwanese version called T-STAT. Study 1 included 15 children with Autism and 15 children with Developmental Delay (DD) or language impairment (LI) aged between 24 and 35 months. Study 2 had 77 young children with Autism, PDD-NOS, or DD/LI as a…

  15. Modulation of Stat3 Alternative Splicing in Breast Cancer

    DTIC Science & Technology

    2010-09-01

    The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an...Stat3 Alternative Splicing in Breast Cancer Dr. Luca Cartegni Sloan-Kettering Institute New York, NY 10021 Stat3 is a transcription factor...constitutively active in a large number of breast cancers and other tumors, where it works as a central player in the activation of multiple oncogenic pathways

  16. Loss of STAT1 protects hair cells from ototoxicity through modulation of STAT3, c-Jun, Akt, and autophagy factors

    PubMed Central

    Levano, S; Bodmer, D

    2015-01-01

    Hair cell damage is a side effect of cisplatin and aminoglycoside use. The inhibition or attenuation of this process is a target of many investigations. There is growing evidence that STAT1 deficiency decreases cisplatin-mediated ototoxicity; however, the role of STAT function and the molecules that act in gentamicin-mediated toxicity have not been fully elucidated. We used mice lacking STAT1 to investigate the effect of STAT1 ablation in cultured organs treated with cisplatin and gentamicin. Here we show that ablation of STAT1 decreased cisplatin toxicity and attenuated gentamicin-mediated hair cell damage. More TUNEL-positive hair cells were observed in explants of wild-type mice than that of STAT1−/− mice. Although cisplatin increased serine phosphorylation of STAT1 in wild-type mice and diminished STAT3 expression in wild-type and STAT1−/− mice, gentamicin increased tyrosine phosphorylation of STAT3 in STAT1−/− mice. The early inflammatory response was manifested in the upregulation of TNF-α and IL-6 in cisplatin-treated explants of wild-type and STAT1−/− mice. Expression of the anti-inflammatory cytokine IL-10 was altered in cisplatin-treated explants, upregulated in wild-type explants, and downregulated in STAT1−/− explants. Cisplatin and gentamicin triggered the activation of c-Jun. Activation of Akt was observed in gentamicin-treated explants from STAT1−/− mice. Increased levels of the autophagy proteins Beclin-1 and LC3-II were observed in STAT1−/− explants. These data suggest that STAT1 is a central player in mediating ototoxicity. Gentamicin and cisplatin activate different downstream factors to trigger ototoxicity. Although cisplatin and gentamicin triggered inflammation and activated apoptotic factors, the absence of STAT1 allowed the cells to overcome the effects of these drugs. PMID:26673664

  17. Comment on ``On the imaginary-real ratio rule of power spectra'' [J. Math. Phys. 50, 063301 (2009)

    NASA Astrophysics Data System (ADS)

    Chen, Yong

    2010-04-01

    For the three-state ergodic Markov process, the condition of all the fluctuation spectra (i.e., power spectra) with respect to real observables being monotonic over [0,+∞) [Y. Chen, Fluct. Noise Lett. 7, L181 (2007) (Theorem 2.6)] is deduced from Theorem 1 of Qian and Xie [J. Math. Phys. 50, 063301 (2009)]. In addition, we present two examples using Theorem 3 of Qian and Xie [J. Math. Phys. 50, 063301 (2009)].

  18. Digging Movie from Phoenix's Sol 18

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Surface Stereo Imager on NASA's Phoenix Mars Lander recorded the images combined into this movie of the lander's Robotic Arm enlarging and combining the two trenches informally named 'Dodo' (left) and 'Goldilocks.'

    The 21 images in this sequence were taken over a period of about 2 hours during Phoenix's Sol 18 (June 13, 2008), or the 18th Martian day since landing.

    The main purpose of the Sol 18 dig was to dig deeper for learning the depth of a hard underlying layer. A bright layer, possibly ice, was increasingly exposed as the digging progressed. Further digging and scraping in the combined Dodo-Goldilocks trench was planned for subsequent sols.

    The combined trench is about 20 centimeters (about 8 inches) wide. The depth at the end of the Sol 18 digging is 5 to 6 centimeters (about 2 inches).

    The Goldilocks trench was the source of soil samples 'Baby Bear' and 'Mama Bear,' which were collected on earlier sols and delivered to instruments on the lander deck. The Dodo trench was originally dug for practice in collecting and depositing soil samples.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  19. Activation of epithelial STAT3 regulates intestinal homeostasis.

    PubMed

    Neufert, Clemens; Pickert, Geethanjali; Zheng, Yan; Wittkopf, Nadine; Warntjen, Moritz; Nikolaev, Alexei; Ouyang, Wenjun; Neurath, Markus F; Becker, Christoph

    2010-02-15

    The intestinal epithelium that lines the mucosal surface along the GI-tract is a key player for the intestinal homeostasis of the healthy individual. In case of a mucosal damage or a barrier defect as seen in patients with inflammatory bowel disease, the balance is disturbed, and translocation of intestinal microbes to the submucosa is facilitated. We recently demonstrated a pivotal role of STAT3 activation in intestinal epithelial cells (IEC) for the restoration of the balance at the mucosal surface of the gut in an experimental colitis model. STAT3 was rapidly induced in intestinal epithelial cells upon challenge of mice in both experimental colitis and intestinal wound healing models. STAT3 activation was found to be dispensable in the steady-state conditions but was important for efficient regeneration of the epithelium in response to injury. Here, we extend our previous findings by showing epithelial STAT3 activation in human patients suffering from IBD and provide additional insights how the activation of epithelial STAT3 by IL-22 regulates intestinal homeostasis and mucosal wound healing. We also demonstrate that antibody-mediated neutralization of IL-22 has little impact on the development of experimental colitis in mice, but significantly delays recovery from colitis. Thus, our data suggest that targeting the STAT3 signaling pathway in IEC is a promising therapeutic approach in situations when the intestinal homeostasis is disturbed, e.g., as seen in Crohn's disease or Ulcerative colitis.

  20. STAT signaling in mammary gland differentiation, cell survival and tumorigenesis.

    PubMed

    Haricharan, S; Li, Y

    2014-01-25

    The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programmed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer.

  1. Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein.

    PubMed

    Kotha, Anupama; Sekharam, Madhavi; Cilenti, Lucia; Siddiquee, Khandaker; Khaled, Annette; Zervos, Antonis S; Carter, Bradford; Turkson, James; Jove, Richard

    2006-03-01

    Resveratrol is a naturally occurring phytoalexin with antioxidant and antiinflammatory properties. Recent studies suggest that resveratrol possesses anticancer effects, although its mechanism of action is not well understood. We now show that resveratrol inhibits Src tyrosine kinase activity and thereby blocks constitutive signal transducer and activator of transcription 3 (Stat3) protein activation in malignant cells. Analyses of resveratrol-treated malignant cells harboring constitutively-active Stat3 reveal irreversible cell cycle arrest of v-Src-transformed mouse fibroblasts (NIH3T3/v-Src), human breast (MDA-MB-231), pancreatic (Panc-1), and prostate carcinoma (DU145) cell lines at the G0-G1 phase or at the S phase of human breast cancer (MDA-MB-468) and pancreatic cancer (Colo-357) cells, and loss of viability due to apoptosis. By contrast, cells treated with resveratrol, but lacking aberrant Stat3 activity, show reversible growth arrest and minimal loss of viability. Moreover, in malignant cells harboring constitutively-active Stat3, including human prostate cancer DU145 cells and v-Src-transformed mouse fibroblasts (NIH3T3/v-Src), resveratrol treatment represses Stat3-regulated cyclin D1 as well as Bcl-xL and Mcl-1 genes, suggesting that the antitumor cell activity of resveratrol is in part due to the blockade of Stat3-mediated dysregulation of growth and survival pathways. Our study is among the first to identify Src-Stat3 signaling as a target of resveratrol, further defining the mechanism of antitumor cell activity of resveratrol and raising its potential application in tumors with an activated Stat3 profile.

  2. The Ubiquitin Ligase TRAF6 Negatively Regulates the JAK-STAT Signaling Pathway by Binding to STAT3 and Mediating Its Ubiquitination

    PubMed Central

    Jin, Chaozhi; Chen, Hui; Leng, Ling; He, Fuchu; Wang, Jian

    2012-01-01

    STAT3 is a key transcription factor that mediates various cellular and organismal processes, such as cell growth, apoptosis, immune response and cancer. However, the molecular mechanisms of STAT3 regulation remain poorly understood. Here, we identified TRAF6 as a new STAT3 interactor. TRAF6 augmented the ubiquitination of STAT3 and deactivated its transcriptional activity induced by IFNα stimulation or overexpressed with JAK2. Both the RING domain and the TRAF-type zinc finger domain of TRAF6 were indispensable for STAT3 deactivation. Accordingly, TRAF6 also down-regulated the expression of two known STAT3 target genes, CRP and ACT. Therefore, we showed that TRAF6 is a new regulator of JAK/STAT signaling and provide a new mechanistic explanation for the crosstalk between the NF-κB and the JAK-STAT pathways. PMID:23185365

  3. Gel-sol synthesis of rutile nanoparticles.

    PubMed

    Verhovšek, Dejan; Lešnik, Maja; Veronovski, Nika; Samardžija, Zoran; Žagar, Kristina; Čeh, Miran

    2014-01-01

    Titanium dioxide (TiO(2)) rutile nanoparticles were synthesized at temperatures below 100 °C using a gel-sol process that provides control of the final particles' characteristics, such as the nanoparticle size, morphology, crystal structure and crystallinity. The synthesized rutile nanoparticles were analyzed using X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results show that the gel-sol process allows control over the final nanoparticle characteristics with the proper choice of reaction parameters. The most profound influence on the nanoparticles' properties is achieved by the type and concentration of the acid used in the reaction mixture. The gel-sol synthesis resulted in anisotropic rutile nanoparticles that are 60-160 nm long, depending on the reaction parameters, and have an aspect ratio of about 5. A reaction mechanism is presented, explaining the influence of various reaction parameters on the characteristics of the TiO(2) nanoparticles.

  4. Opportunity's Surroundings on Sol 1687 (Vertical)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this 360-degree view of the rover's surroundings on the 1,687th Martian day, or sol, of its surface mission (Oct. 22, 2008).

    Opportunity had driven 133 meters (436 feet) that sol, crossing sand ripples up to about 10 centimeters (4 inches) tall. The tracks visible in the foreground are in the east-northeast direction.

    Opportunity's position on Sol 1687 was about 300 meters southwest of Victoria Crater. The rover was beginning a long trek toward a much larger crater, Endeavour, about 12 kilometers (7 miles) to the southeast.

    This view is presented as a vertical projection with geometric seam correction.

  5. Opportunity's Surroundings on Sol 1687 (Polar)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this 360-degree view of the rover's surroundings on the 1,687th Martian day, or sol, of its surface mission (Oct. 22, 2008).

    Opportunity had driven 133 meters (436 feet) that sol, crossing sand ripples up to about 10 centimeters (4 inches) tall. The tracks visible in the foreground are in the east-northeast direction.

    Opportunity's position on Sol 1687 was about 300 meters southwest of Victoria Crater. The rover was beginning a long trek toward a much larger crater, Endeavour, about 12 kilometers (7 miles) to the southeast.

    This view is presented as a polar projection with geometric seam correction.

  6. Before & After of Rasping on Sol 56

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This animation combines two images of the trench informally named 'Snow White' taken by the Surface Stereo Imager on NASA's Phoenix Mars Lander on July 21, 2008, during the lander's 56th Martian day, or sol, since landing.

    The earlier Sol 56 image is the one without a shadow falling across the lower right corner of the image. It was taken after Phoenix had used its motorized rasp to get some material from the trench into the scoop on the lander's robotic arm. The later Sol 56 image was taken after the arm had scraped clean an area that includes the rasping site.

    The trench is about 23 centimeters (9 inches) wide. These images were taken through the camera's red filter.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is led by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  7. The Shc1 adaptor simultaneously balances Stat1 and Stat3 activity to promote breast cancer immune suppression

    PubMed Central

    Ahn, Ryuhjin; Sabourin, Valérie; Bolt, Alicia M.; Hébert, Steven; Totten, Stephanie; De Jay, Nicolas; Festa, Maria Carolina; Young, Yoon Kow; Im, Young Kyuen; Pawson, Tony; Koromilas, Antonis E.; Muller, William J.; Mann, Koren K.; Kleinman, Claudia L.; Ursini-Siegel, Josie

    2017-01-01

    Tyrosine kinase signalling within cancer cells is central to the establishment of an immunosuppressive microenvironment. Although tyrosine kinase inhibitors act, in part, to augment adaptive immunity, the increased heterogeneity and functional redundancy of the tyrosine kinome is a hurdle to achieving durable responses to immunotherapies. We previously identified the Shc1 (ShcA) scaffold, a central regulator of tyrosine kinase signalling, as essential for promoting breast cancer immune suppression. Herein we show that the ShcA pathway simultaneously activates STAT3 immunosuppressive signals and impairs STAT1-driven immune surveillance in breast cancer cells. Impaired Y239/Y240-ShcA phosphorylation selectively reduces STAT3 activation in breast tumours, profoundly sensitizing them to immune checkpoint inhibitors and tumour vaccines. Finally, the ability of diminished tyrosine kinase signalling to initiate STAT1-driven immune surveillance can be overcome by compensatory STAT3 hyperactivation in breast tumours. Our data indicate that inhibition of pY239/240-ShcA-dependent STAT3 signalling may represent an attractive therapeutic strategy to sensitize breast tumours to multiple immunotherapies. PMID:28276425

  8. The Shc1 adaptor simultaneously balances Stat1 and Stat3 activity to promote breast cancer immune suppression.

    PubMed

    Ahn, Ryuhjin; Sabourin, Valérie; Bolt, Alicia M; Hébert, Steven; Totten, Stephanie; De Jay, Nicolas; Festa, Maria Carolina; Young, Yoon Kow; Im, Young Kyuen; Pawson, Tony; Koromilas, Antonis E; Muller, William J; Mann, Koren K; Kleinman, Claudia L; Ursini-Siegel, Josie

    2017-03-09

    Tyrosine kinase signalling within cancer cells is central to the establishment of an immunosuppressive microenvironment. Although tyrosine kinase inhibitors act, in part, to augment adaptive immunity, the increased heterogeneity and functional redundancy of the tyrosine kinome is a hurdle to achieving durable responses to immunotherapies. We previously identified the Shc1 (ShcA) scaffold, a central regulator of tyrosine kinase signalling, as essential for promoting breast cancer immune suppression. Herein we show that the ShcA pathway simultaneously activates STAT3 immunosuppressive signals and impairs STAT1-driven immune surveillance in breast cancer cells. Impaired Y239/Y240-ShcA phosphorylation selectively reduces STAT3 activation in breast tumours, profoundly sensitizing them to immune checkpoint inhibitors and tumour vaccines. Finally, the ability of diminished tyrosine kinase signalling to initiate STAT1-driven immune surveillance can be overcome by compensatory STAT3 hyperactivation in breast tumours. Our data indicate that inhibition of pY239/240-ShcA-dependent STAT3 signalling may represent an attractive therapeutic strategy to sensitize breast tumours to multiple immunotherapies.

  9. Constitutive Phosphorylation of STAT3 by the CK2-BLNK-CD5 Complex.

    PubMed

    Rozovski, Uri; Harris, David M; Li, Ping; Liu, Zhiming; Jain, Preetesh; Veletic, Ivo; Ferrajoli, Alessandra; Burger, Jan; O'Brien, Susan; Bose, Prithviraj; Thompson, Philip; Jain, Nitin; Wierda, William; Keating, Michael J; Estrov, Zeev

    2017-01-27

    In chronic lymphocytic leukemia (CLL), STAT3 is constitutively phosphorylated on serine 727 and plays a role in the pathobiology of CLL. However, what induces constitutive phosphorylation of STAT3 is currently unknown. Mass spectrometry was used to identify casein kinase 2 (CK2), a serine/threonine kinase that co-immunoprecipitated with serine phosphorylated STAT3 (pSTAT3). Furthermore, activated CK2 incubated with recombinant STAT3 induced phosphorylation of STAT3 on serine 727. Although STAT3 and CK2 are present in normal B- and T-cells, STAT3 is not constitutively phosphorylated in these cells. Further study found that CD5 and BLNK co-expressed in CLL, but not in normal B- or T-cells, are required for STAT3 phosphorylation. To elucidate the relationship of CD5 and BLNK to CK2 and STAT3, STAT3 was immunoprecipitated from CLL cells and CK2, CD5, and BLNK were detected in the immunoprecipitate. Conversely, STAT3, CD5, and BLNK were in the immunoprecipitate of CLL cells immunoprecipitated with CK2 antibodies. Furthermore, siRNA knockdown of CD5 or BLNK, or treatment with CD5-neutralizing antibodies significantly reduced the levels of serine pSTAT3 in CLL cells. Finally, confocal microscopy determined that CD5 is cell membrane bound and fractionation studies revealed that the CK2/CD5/BLNK/STAT3 complex remains in the cytoplasm, whereas serine pSTAT3 is shuttled to the nucleus.

  10. Characterization of a dominant-active STAT that promotes tumorigenesis in Drosophila

    PubMed Central

    Ekas, Laura A.; Cardozo, Timothy J.; Flaherty, Maria Sol; McMillan, Elizabeth A.; Gonsalves, Foster C.; Bach, Erika A.

    2010-01-01

    Little is known about the molecular mechanisms by which STAT proteins promote tumorigenesis. Drosophila is an ideal system for investigating this issue, as there is a single STAT (Stat92E), and its hyperactivation causes overgrowths resembling human tumors. Here we report the first identification of a dominant-active Stat92E protein, Stat92EΔNΔC, which lacks both N- and C-termini. Mis-expression of Stat92EΔNΔC in vivo causes melanotic tumors, while in vitro it transactivates a Stat92E-luciferase reporter in the absence of stimulation. These gain-of-function phenotypes require phosphorylation of Y711 and dimer formation with full-length Stat92E. Furthermore, a single point mutation, an R442P substitution in the DNA-binding domain, abolishes Stat92E function. Recombinant Stat92ER442P translocates to the nucleus following activation but fails to function in all assays tested. Interestingly, R442 is conserved in most STATs in higher organisms, suggesting conservation of function. Modeling of Stat92E indicates that R442 may contact the minor groove of DNA via invariant TC bases in the consensus binding element bound by all STAT proteins. We conclude that the N- and C- termini function unexpectedly in negatively regulating Stat92E activity, possibly by decreasing dimer dephosphorylation or increasing stability of DNA interaction, and that Stat92ER442 has a nuclear function by altering dimer:DNA binding. PMID:20501334

  11. Neutron detector using sol-gel absorber

    DOEpatents

    Hiller, John M.; Wallace, Steven A.; Dai, Sheng

    1999-01-01

    An neutron detector composed of fissionable material having ions of lithium, uranium, thorium, plutonium, or neptunium, contained within a glass film fabricated using a sol-gel method combined with a particle detector is disclosed. When the glass film is bombarded with neutrons, the fissionable material emits fission particles and electrons. Prompt emitting activated elements yielding a high energy electron contained within a sol-gel glass film in combination with a particle detector is also disclosed. The emissions resulting from neutron bombardment can then be detected using standard UV and particle detection methods well known in the art, such as microchannel plates, channeltrons, and silicon avalanche photodiodes.

  12. Spirit 360-Degree View on Sol 409

    NASA Technical Reports Server (NTRS)

    2005-01-01

    NASA's Mars Exploration Rover Spirit used its navigation camera to take the images combined into this 360-degree view of the rover's surroundings on Spirit's 409th martian day, or sol (Feb. 26, 2005). Spirit had driven 2 meters (7 feet) on this sol to get in position on 'Cumberland Ridge' for looking into 'Tennessee Valley' to the east. This location is catalogued as Spirit's Site 108. Rover-wheel tracks from climbing the ridge are visible on the right. The summit of 'Husband Hill' is at the center, to the south. This view is presented in a cylindrical projection with geometric and brightness seam correction.

  13. Spirit Beside 'Home Plate,' Sol 1809

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA Mars Exploration Rover Spirit used its navigation camera to take the images assembled into this 120-degree view southward after a short drive during the 1,809th Martian day, or sol, of Spirit's mission on the surface of Mars (February 3, 2009).

    Spirit had driven about 2.6 meters (8.5 feet) that sol, continuing a clockwise route around a low plateau called 'Home Plate.' In this image, the rocks visible above the rovers' solar panels are on the slope at the northern edge of Home Plate.

    This view is presented as a cylindrical projection with geometric seam correction.

  14. Sol-gel-derived biomaterials of silica and carrageenans.

    PubMed

    Shchipunov, Yurii A

    2003-12-01

    A new precursor, tetrakis(2-hydroxyethyl) orthosilicate (THEOS), introduced by Hoffmann et al. (J. Phys. Chem. B 106 (2002) 1528-1533), was used to synthesize monolithic hybrid biomaterials on the basis of silica and three main types of carrageenans, kappa-, iota-, and lambda-carrageenans. The advantage of THEOS over the currently applied TEOS and TMOS is in its complete solubility in water. This negated the need to add organic solvents, thus excluding a denaturating effect on biopolymers. In their turn, carrageenans introduced into the precursor solution made use of common catalysts unneeded to trigger the sol-gel transition. It was found that they promoted the mineralization, acting as a template for the inorganic component. The kinetics of sol-gel processes, mechanical properties, phase behavior, and structure of novel hybrid biomaterials were studied by dynamic rheology, differential scanning calorimetry, and scanning electron microscopy. The material properties were regulated by both the precursor and carrageenan. The increase of silicate concentration led to a rise in the stiffness and brittleness of the material, whereas the polysaccharide addition made it softer and more elastic. It was shown that the formation and properties of mixed gels were determined by the nature of carrageenan. kappa-Carrageenans brought about shrinkage of hybrid materials that led to water separation, while iota- and lambda-carrageenans did not induce the syneresis. This is in line with the difference in polysaccharide properties when they are in aqueous solutions without silicate. Furthermore, kappa- and iota-carrageenans experienced a thermoreversible phase transition in the hybrid materials owing to the helix-coil transition. This resulted in a step like change in the mechanical properties of mixed systems in the corresponding temperature range. lambda-Carrageenan is a nongelling polysaccharide, which is why the rheological parameters of its hybrid gel were unchanged with the

  15. Leptin-Induced JAK/STAT Signaling and Cancer Growth

    PubMed Central

    Mullen, McKay; Gonzalez-Perez, Ruben Rene

    2016-01-01

    Growth factor and cytokine signaling can influence the development of several cancer types. One of the key players in the development of cancer is the Janus kinas (JAK) signal transducer of activators of transcription (STAT) signaling pathway. The majority of growth factors and cytokine interactions with their membrane-bound receptors trigger JAK-STAT activation. The influential relationship between obesity and cancer is a fact. However, there is a complex sequence of events contributing to the regulation of this mechanism to promote tumor growth, yet to be fully elucidated. The JAK-STAT pathway is influenced by obesity-associated changes that have been shown to impact cancer growth and progression. This intricate process is highly regulated by a vast array of adipokines and cytokines that exert their pleiotropic effects on cancer cells to enhance metastasis to distant target sites. Leptin is a cytokine, or more precise, an adipokine secreted mainly by adipose tissue that requires JAK-STAT activation to exert its biological functions. Leptin is the central regulator of energy balance and appetite. Leptin binding to its receptor OB-R in turn activates JAK-STAT, which induces proliferation, angiogenesis, and anti-apoptotic events in normal cells and malignant cells expressing the receptor. Leptin also induces crosstalk with Notch and IL-1 (NILCO), which involves other angiogenic factors promoting tumor growth. Therefore, the existence of multiple novel classes of therapeutics that target the JAK/STAT pathway has significant clinical implications. Then, the identification of the signaling networks and factors that regulate the obesity-cancer link to which potential pharmacologic interventions can be implemented to inhibit tumor growth and metastasis. In this review, we will discuss the specific relationship between leptin-JAK-STAT signaling and cancer. PMID:27472371

  16. PyDecay/GraphPhys: A Unified Language and Storage System for Particle Decay Process Descriptions

    SciTech Connect

    Dunietz, Jesse N.; /MIT /SLAC

    2011-06-22

    To ease the tasks of Monte Carlo (MC) simulation and event reconstruction (i.e. inferring particle-decay events from experimental data) for long-term BaBar data preservation and analysis, the following software components have been designed: a language ('GraphPhys') for specifying decay processes, common to both simulation and data analysis, allowing arbitrary parameters on particles, decays, and entire processes; an automated visualization tool to show graphically what decays have been specified; and a searchable database storage mechanism for decay specifications. Unlike HepML, a proposed XML standard for HEP metadata, the specification language is designed not for data interchange between computer systems, but rather for direct manipulation by human beings as well as computers. The components are interoperable: the information parsed from files in the specification language can easily be rendered as an image by the visualization package, and conversion between decay representations was implemented. Several proof-of-concept command-line tools were built based on this framework. Applications include building easier and more efficient interfaces to existing analysis tools for current projects (e.g. BaBar/BESII), providing a framework for analyses in future experimental settings (e.g. LHC/SuperB), and outreach programs that involve giving students access to BaBar data and analysis tools to give them a hands-on feel for scientific analysis.

  17. Comment on ``Modeling shock waves in orthotropic elastic materials'' [J. Appl. Phys. 104, 044904 (2008)

    NASA Astrophysics Data System (ADS)

    Lukyanov, Alexander A.

    2010-09-01

    This comment identifies two main problems with the paper Vignjevic et al. [J. Appl. Phys. 104, 044904 (2008)] related to shock waves modeling in composites. (1) The authors claim that they have proposed two different stress decompositions based on the assumption that the stress tensor is split into two components: one component is due to volumetric strain and the other is due to deviatoric strain. Following this, the authors defined a pressure as the state of stress resulting only from volumetric deformation. However, neither the first nor second decomposition of the stress tensor proposed by the authors provides a procedure for separating the material volumetric compression from the deviatoric strain tensor which results in a state of stress corresponding to volumetric deformation. Furthermore, the uniquely correct decomposition of the stress tensor based on the same second order material tensors has already been published (see, for example, [Int. J. Plast. 24, 140 (2008)]). Also, the second decomposition of the stress tensor includes serious mistakes and inconsistencies. (2) In addition, the numerical simulation results proposed by the authors cannot be justified. An analytical calculation of the Hugoniot stress levels and the acoustic speed of sound through the thickness orientation for a selected carbon-fiber epoxy composite show that the stress decompositions and material properties reported by the authors do not agree with the experimental data for this material and, more importantly, contradict the shock wave stability requirements.

  18. Sol-Gel Synthesis Of Aluminoborosilicate Powders

    NASA Technical Reports Server (NTRS)

    Bull, Jeffrey; Leiser, Daniel; Selvaduray, Guna

    1992-01-01

    Application of sol-gel process to synthesis of aluminoborosilicate powders shows potential for control of microstructures of materials. Development of materials having enhanced processing characteristics prove advantageous in extending high-temperature endurance of fibrous refractory composite insulation made from ceramic fibers.

  19. Opportunity's View After Drive on Sol 1806

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings just after driving 60.86 meters (200 feet) on the 1,806th Martian day, or sol, of Opportunity's surface mission (Feb. 21, 2009). North is at the center; south at both ends.

    Tracks from the drive extend northward across dark-toned sand ripples and light-toned patches of exposed bedrock in the Meridiani Planum region of Mars. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches).

    Engineers designed the Sol 1806 drive to be driven backwards as a strategy to redistribute lubricant in the rovers wheels. The right-front wheel had been showing signs of increased friction.

    The rover's position after the Sol 1806 drive was about 2 kilometer (1.2 miles) south southwest of Victoria Crater. Cumulative odometry was 14.74 kilometers (9.16 miles) since landing in January 2004, including 2.96 kilometers (1.84 miles) since climbing out of Victoria Crater on the west side of the crater on Sol 1634 (August 28, 2008).

    This view is presented as a cylindrical projection with geometric seam correction.

  20. STATs Shape the Active Enhancer Landscape of T Cell Populations

    PubMed Central

    Vahedi, Golnaz; Takahashi, Hayato; Nakayamada, Shingo; Sun, Hong-wei; Sartorelli, Vittorio; Kanno, Yuka; O’Shea, John J.

    2012-01-01

    SUMMARY Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. While enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4+ T cells as a model of differentiation, mapping the acquisition of cell-type-specific enhancer elements in T-helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the acquisition of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells. PMID:23178119

  1. Structural Tailoring of Advanced Turboprops (STAT). Theoretical manual

    NASA Technical Reports Server (NTRS)

    Brown, K. W.

    1992-01-01

    This manual describes the theories in the Structural Tailoring of Advanced Turboprops (STAT) computer program, which was developed to perform numerical optimizations on highly swept propfan blades. The optimization procedure seeks to minimize an objective function, defined as either direct operating cost or aeroelastic differences between a blade and its scaled model, by tuning internal and external geometry variables that must satisfy realistic blade design constraints. The STAT analyses include an aerodynamic efficiency evaluation, a finite element stress and vibration analysis, an acoustic analysis, a flutter analysis, and a once-per-revolution (1-p) forced response life prediction capability. The STAT constraints include blade stresses, blade resonances, flutter, tip displacements, and a 1-P forced response life fraction. The STAT variables include all blade internal and external geometry parameters needed to define a composite material blade. The STAT objective function is dependent upon a blade baseline definition which the user supplies to describe a current blade design for cost optimization or for the tailoring of an aeroelastic scale model.

  2. Three STATs are involved in the regulation of the expression of antimicrobial peptides in the triangle sail mussel, Hyriopsis cumingii.

    PubMed

    Dai, Yun-Jia; Hui, Kai-Min; Zhang, Ying-Hao; Liu, Yan; Wang, Yu-Qing; Zhao, Li-Juan; Lin, Li; Chai, Lian-Qin; Wei, Shun; Lan, Jiang-Feng

    2017-02-16

    Janus kinase (Jak) and signal transducers and activators of transcription (STAT) signaling pathway is associated in antiviral and antibacterial immune response. Previous studies primarily investigated the function of STATs in mammals. For most invertebrates, only one STAT was found in each species, such as STAT92E was found in Drosophila melanogaster. The studies, which focus on the functional difference between various STATs in the same species of invertebrate, are limited. In the present study, three STATs (HcSTAT1, HcSTAT2 and HcSTAT3) were identified in triangle shell pearl mussel, Hyriopsis cumingii. Phylogenetic analysis showed that HcSTAT1 and HcSTAT3 were clustered with Homo sapiens STAT5, and HcSTAT2 was clustered with Pinctada fucata STAT and Crassostea gigas STAT6. All three STATs could be detected in all tested tissues (hemocytes, hepatopancreas, gill, mantle and foot), and were induced expression when challenged with Staphylococcus aureus or Aeromonas hydrophilia in hemocytes and hepatopancreas. HcSTAT1 regulated the expression of HcDef, HcWAP, HcThe and HcTNF. The expression of HcWAP and HcTNF was down-regulated in HcSTAT2-RNAi mussel. And HcSTAT3 affected the expression of HcTNF. The study is the first report of different functions in antibacterial immune responses between STATs in mollusks.

  3. [Amino acids 395-416 in DNA binding domain of STAT4 is involved in IL-12-induced nuclear import of STAT4].

    PubMed

    Huang, Yu-Mei; Wen, Ya-Ping; Li, Xuan-An; Yuan, Yuan; Luo, Qi-Zhi; Li, Ming

    2012-08-25

    The purpose of the present study is to explore the mechanism of IL-12-induced nuclear import of signal transducer and activator of transcription 4 (STAT4). Assayed by analyses of homology alignment of STATs, amino acids 395-416 in DNA binding domain was found to be a potential dimer-specific nuclear localization signal (dsNLS) of STAT4. Therefore, several plasmids were constructed. Wild-type STAT4 was inserted into the SalI and BamHI sites of pEGFP-C1 for the construction of plasmid pEGFP-STAT4. The DNA fragment of STAT4 with the deletion of amino acids 395-416 was amplified by RCR and introduced into the SalI and BamHI sites of pEGFP-C1 which was named pEGFP-STAT4-Del. Classic NLS DNA sequence of SV40 T antigen was inserted into the XhoI and HindIII sites of pEGFP-C1. This plasmid was named as pEGFP-NLS and used as a positive control. Plasmid pEGFP-NLS-STAT4-Del was constructed by inserting STAT4-Del into SalI and BamHI sites of pEGFP-NLS. These plasmids were transiently transfected into Caski cells, respectively. The results showed that, after these transfected cells were stimulated by IL-12, wild type STAT4 existed in the cytoplasm at 0 min, and was predominantly localized to the nucleus at 45 min, and distributed in both cytoplasm and nucleus at 60 min, suggesting that STAT4 translocates from cytoplasm into nucleus and finally re-entries into the cytoplasm during the stimulation of IL-12. However, deletion mutant of STAT4 was arrested in cytoplasm during the IL-12 stimulation. Leptomycin B, which specifically blocks protein export from nucleus into cytoplasm, was used to further demonstrate whether STAT4-Del is transferred into nucleus even with stimulation of IL-12. After the transfected cells were pre-treated by leptomycin B, the wild type STAT4 was mainly localized in nucleus after the IL-12 stimulation, suggesting that STAT4 was translocated from cytoplasm into nucleus by the stimulation of IL-12. On the other hand, the deletion mutant of STAT4 distributed

  4. Erratum: Studying the precision of ray tracing techniques with Szekeres models [Phys. Rev. D 92, 023532 (2015)

    NASA Astrophysics Data System (ADS)

    Koksbang, S. M.; Hannestad, S.

    2015-09-01

    This erratum serves to give corrections of two errors made in Koksbang and Hannestad [Phys. Rev. D, 92, 023532 (2015)]. One error consists of having used the expression for the Doppler convergence for a flat background to study the convergence on curved backgrounds. The other error which was made, is a typo in the numerical code used to study the convergence in onion models with curved backgrounds. After correcting this typo, the results of Sec. VI A in Koksbang and Hannestad [Phys. Rev. D, 92, 023532 (2015)] were recomputed. Contrary to the original results, the new results show that the ray-tracing scheme studied in Koksbang and Hannestad [Phys. Rev. D, 92, 023532 (2015)] can reproduce the exact results in LTB onion models very well. The corrections and new results are described more elaborately below.

  5. A STAT-1 knockout mouse model for Machupo virus pathogenesis

    PubMed Central

    2011-01-01

    Background Machupo virus (MACV), a member of the Arenaviridae, causes Bolivian hemorrhagic fever, with ~20% lethality in humans. The pathogenesis of MACV infection is poorly understood, and there are no clinically proven treatments for disease. This is due, in part, to a paucity of small animal models for MACV infection in which to discover and explore candidate therapeutics. Methods Mice lacking signal transducer and activator of transcription 1 (STAT-1) were infected with MACV. Lethality, viral replication, metabolic changes, hematology, histopathology, and systemic cytokine expression were analyzed throughout the course of infection. Results We report here that STAT-1 knockout mice succumbed to MACV infection within 7-8 days, and presented some relevant clinical and histopathological manifestations of disease. Furthermore, the model was used to validate the efficacy of ribavirin in protection against infection. Conclusions The STAT-1 knockout mouse model can be a useful small animal model for drug testing and preliminary immunological analysis of lethal MACV infection. PMID:21672221

  6. Comment on "Fluid modeling of a high-voltage nanosecond pulsed xenon microdischarge" [Phys. Plasmas 23, 073513 (2016)

    NASA Astrophysics Data System (ADS)

    Koulakis, J.; Bataller, A.; Pree, S.; Putterman, S.

    2016-11-01

    Simulations of sparks in 10 atmosphere Xenon gas by Levko and Raja [Phys. Plasmas 23, 073513 (2016)] are unable to reproduce the experimental fact of their opacity to visible light [Bataller et al., Appl. Phys. Lett. 105, 223501 (2014)]. Levko and Raja have argued the discrepancy is due to enhanced ionization from the probing laser radiation and/or cathode field emission. Having observed comparable opacity in similar systems without probing lasers and without electrodes, we instead argue that the enhanced ionization is a thermodynamic result of dense plasma screening effects that lower the effective ionization potential. Levko and Raja do not adequately address these density effects in their spark discharge simulations.

  7. Comment on "Temperature dependence of atomic vibrations in mono-layer graphene" [J. Appl. Phys. 118, 074302 (2015)

    NASA Astrophysics Data System (ADS)

    Susi, T.; Kotakoski, J.

    2016-02-01

    In an interesting recent study [Allen et al., J. Appl. Phys. 118, 074302 (2015)] (see also their Erratum [Allen et al., J. Appl. Phys. 118, 159902 (2015)]), Allen and co-workers measured the mean square amplitudes of graphene lattice vibrations between 100 and 1300 K and used a simplified theoretical approximation for the acoustic phonon modes to evaluate the maximum phonon wavelengths supported by the lattice. By fitting their data using the smallest wave-vector as the fitting parameter, they found this to be significantly smaller than the physical size of the graphene crystallites.

  8. Comment on “Temperature dependence of atomic vibrations in mono-layer graphene” [J. Appl. Phys. 118, 074302 (2015)

    SciTech Connect

    Susi, T. Kotakoski, J.

    2016-02-14

    In an interesting recent study [Allen et al., J. Appl. Phys. 118, 074302 (2015)] (see also their Erratum [Allen et al., J. Appl. Phys. 118, 159902 (2015)]), Allen and co-workers measured the mean square amplitudes of graphene lattice vibrations between 100 and 1300 K and used a simplified theoretical approximation for the acoustic phonon modes to evaluate the maximum phonon wavelengths supported by the lattice. By fitting their data using the smallest wave-vector as the fitting parameter, they found this to be significantly smaller than the physical size of the graphene crystallites.

  9. Comment on ``The application of the thermodynamic perturbation theory to study the hydrophobic hydration'' [J. Chem. Phys. 139, 024101 (2013)

    NASA Astrophysics Data System (ADS)

    Graziano, Giuseppe

    2013-09-01

    It is shown that the behaviour of the hydration thermodynamic functions obtained in the 3D Mercedes-Benz model of water by Mohoric et al. [J. Chem. Phys. 139, 024101 (2013)] is not qualitatively correct with respect to experimental data for a solute whose diameter is 1.5-fold larger than that of a water molecule. It is also pointed out that the failure is due to the fact that the used 3D Mercedes-Benz model of water [A. Bizjak, T. Urbic, V. Vlachy, and K. A. Dill, J. Chem. Phys. 131, 194504 (2009)] does not reproduce in a quantitatively correct manner the peculiar temperature dependence of water density.

  10. Bcl6 promotes osteoblastogenesis through Stat1 inhibition

    SciTech Connect

    Fujie, Atsuhiro; Funayama, Atsushi; Miyauchi, Yoshiteru; Sato, Yuiko; Kobayashi, Tami; Kanagawa, Hiroya; Katsuyama, Eri; Hao, Wu; Tando, Toshimi; Watanabe, Ryuichi; Morita, Mayu; Miyamoto, Kana; Kanaji, Arihiko; Morioka, Hideo; Matsumoto, Morio; Toyama, Yoshiaki; Miyamoto, Takeshi

    2015-02-13

    Bone mass is tightly controlled by a balance between osteoclast and osteoblast activities. Although these cell types mature via different pathways, some factors reportedly regulate differentiation of both. Here, in a search for factors governing osteoblastogenesis but also expressed in osteoclasts to control both cell types by one molecule, we identified B cell lymphoma 6 (Bcl6) as one of those factors and show that it promotes osteoblast differentiation. Bcl6 was previously shown to negatively regulate osteoclastogenesis. We report that lack of Bcl6 results in significant inhibition of osteoblastogensis in vivo and in vitro and in defects in secondary ossification center formation in vivo. Signal transducer and activator of transcription 1 (Stat1) reportedly attenuates osteoblast differentiation by inhibiting nuclear translocation of runt-related transcription factor 2 (Runx2), which is essential for osteoblast differentiation. We found that lack of Bcl6 resulted in significant elevation of Stat1 mRNA and protein expression in osteoblasts and showed that Stat1 is a direct target of Bcl6 using a chromatin immune-precipitation assay. Mice lacking both Bcl6 and Stat1 (DKO) exhibited significant rescue of bone mass and osteoblastic parameters as well as partial rescue of secondary ossification center formation compared with Bcl6-deficient mice in vivo. Altered osteoblastogenesis in Bcl6-deficient cells was also restored in DKO in vitro. Thus, Bcl6 plays crucial roles in regulating both osteoblast activation and osteoclast inhibition. - Highlights: • Bcl6 is required for osteoblast differentiation. • Bcl6{sup −/−} mice exhibited altered osteoblastogenesis and reduced bone mass in vivo and in vitro. • We identified Stat1 as a direct target of Bcl6 in osteoblasts. • Bcl6 and Stat1 doubly deficient mice exhibited rescued bone phenotypes compared with Bcl6{sup −/−} mice.

  11. Evaluation of STAT medication ordering process in a community hospital

    PubMed Central

    Walsh., Kim; Schwartz., Barbara

    Background: In most health care facilities, problems related to delays in STAT medication order processing time are of common concern. Objective: The purpose of this study was to evaluate processing time for STAT orders at Kimball Medical Center. Methods: All STAT orders were reviewed to determine processing time; order processing time was also stratified by physician order entry (physician entered (PE) orders vs. non-physician entered (NPE) orders). Collected data included medication ordered, indication, time ordered, time verified by pharmacist, time sent from pharmacy, and time charted as given to the patient. Results: A total of 502 STAT orders were reviewed and 389 orders were included for analysis. Overall, median time was 29 minutes, IQR 16–63; p<0.0001.). The time needed to process NPE orders was significantly less than that needed for PE orders (median 27 vs. 34 minutes; p=0.026). In terms of NPE orders, the median total time required to process STAT orders for medications available in the Automated Dispensing Devices (ADM) was within 30 minutes, while that required to process orders for medications not available in the ADM was significantly greater than 30 minutes. For PE orders, the median total time required to process orders for medications available in the ADM (i.e., not requiring pharmacy involvement) was significantly greater than 30 minutes. [Median time = 34 minutes (p<0.001)]. Conclusion: We conclude that STAT order processing time may be improved by increasing the availability of medications in ADM, and pharmacy involvement in the verification process. PMID:27382418

  12. Design, Synthesis and in vitro Characterization of Novel Hybrid Peptidomimetic Inhibitors of STAT3 Protein

    PubMed Central

    Shahani, Vijay M.; Yue, Peibin; Fletcher, Steven; Sharmeen, Sumaiya; Sukhai, Mahadeo A.; Luu, Diana P.; Zhang, Xiaolei; Sun, Hong; Zhao, Wei; Schimmer, Aaron D.; Turkson, James; Gunning, Patrick T.

    2011-01-01

    Aberrant activation of oncogenic signal transducer and activator of transcription 3 (STAT3) protein signaling pathways has been extensively implicated in human cancers. Given STAT3’s prominent dysregulatory role in malignant transformation and tumorigenesis, there has been a significant effort to discover STAT3-specific inhibitors as chemical probes for defining the aberrant STAT3-mediated molecular events that support the malignant phenotype. To identify novel, STAT3-selective inhibitors suitable for interrogating STAT3 signaling in tumor cells, we explored the design of hybrid molecules by conjugating a known STAT3 inhibitory peptidomimetic, ISS610 to the high-affinity STAT3-binding peptide motif derived from the ILR/gp-130. Several hybrid molecules were examined in in vitro biophysical and biochemical studies for inhibitory potency against STAT3. Lead inhibitor 14aa was shown to strongly bind to STAT3 (KD = 900 nM), disrupt STAT3:phosphopeptide complexes (Ki = 5 μM) and suppress STAT3 activity in in vitro DNA-binding activity/ electrophoretic mobility shift assay (EMSA). Moreover, lead STAT3 inhibitor 14aa induced a time-dependent inhibition of constitutive STAT3 activation in v-Src transformed mouse fibroblasts (NIH3T3/v-Src), with 80 % suppression of constitutively-active STAT3 at six hours following treatment of NIH3T3/v-Src. However, STAT3 activity recovered at 24 hours after treatment of cells, suggesting potential degradation of the compound. Results further showed a suppression of aberrant STAT3 activity in NIH3T3/v-Src by the treatment with compound 14aa-OH, which is the non-pTyr version of compound 14aa. The effect of compounds 14aa and 14aa-OH are accompanied by a moderate loss of cell viability. PMID:21216604

  13. CNTF protects neurons from hypoxic injury through the activation of STAT3pTyr705.

    PubMed

    Gu, Ying Li; Gao, Guan Qun; Ma, Ning; Ye, Lin Lin; Zhang, Li Wei; Gao, Xu; Zhang, Zhuo Bo

    2016-12-01

    The aim of the present study was to investigate whether ciliary neurotrophic factor (CNTF) plays its neuroprotective role following hypoxic injury through the activation of signal transducer and activator of transcription 3 (STAT3) signaling. Firstly, to determine whether CNTF exerts its effects via STAT3 following hypoxic injury, cultured neurons from the cerebral cortex of mice were prepared and a neuronal model of hypoxia was then established. The neurons exposed to hypoxia were then pre-treated with CNTF and transfected with small interference RNA (siRNA) targeting STAT3 (STAT3 siRNA) using polybrene, or with STAT3Tyr705 mutant or STAT3Ser727 mutant using an electroporation system. The survival, proliferation and neurite outgrowth of the neurons subjected to different treatments were also determined. RT-qPCR and western blot analysis were employed to examine the expression levels of STAT3, p-STAT3Tyr705 and p-STAT3Ser727 following treatment with CNTF and other treatments. Our results revealed that treatment with CNTF: i) protected neurons from hypoxic injury by promoting survival and neurite growth; ii) induced a significant increase in the levels of STAT3, STAT3pTyr705 and the STAT3pTyr705/STAT3 ratio; it did not however, significantly affect the levels of STAT3pSer727 in the hypoxic cerebral cortex neurons. Transfection of the hypoxic neurons pre-treated with CNTF with STAT3 siRNA or STAT3Tyr705 neutralized the protective effects exerted by CNTF. The findings of our study thus demonstrate that CNTF protects neurons from hypoxic injury through the activation of STAT3pTyr705.

  14. Small-molecule inhibition of STAT3 in radioresistant head and neck squamous cell carcinoma

    PubMed Central

    Bharadwaj, Uddalak; Eckols, T. Kris; Xu, Xuejun; Kasembeli, Moses M.; Chen, Yunyun; Adachi, Makoto; Song, Yongcheng; Mo, Qianxing; Lai, Stephen Y.; Tweardy, David J.

    2016-01-01

    While STAT3 has been validated as a target for treatment of many cancers, including head and neck squamous cell carcinoma (HNSCC), a STAT3 inhibitor is yet to enter the clinic. We used the scaffold of C188, a small-molecule STAT3 inhibitor previously identified by us, in a hit-to-lead program to identify C188-9. C188-9 binds to STAT3 with high affinity and represents a substantial improvement over C188 in its ability to inhibit STAT3 binding to its pY-peptide ligand, to inhibit cytokine-stimulated pSTAT3, to reduce constitutive pSTAT3 activity in multiple HNSCC cell lines, and to inhibit anchorage dependent and independent growth of these cells. In addition, treatment of nude mice bearing xenografts of UM-SCC-17B, a radioresistant HNSCC line, with C188-9, but not C188, prevented tumor xenograft growth. C188-9 treatment modulated many STAT3-regulated genes involved in oncogenesis and radioresistance, as well as radioresistance genes regulated by STAT1, due to its potent activity against STAT1, in addition to STAT3. C188-9 was well tolerated in mice, showed good oral bioavailability, and was concentrated in tumors. Thus, C188-9, either alone or in combination with radiotherapy, has potential for use in treating HNSCC tumors that demonstrate increased STAT3 and/or STAT1 activation. PMID:27027445

  15. STAT3 upregulation in pituitary somatotroph adenomas induces growth hormone hypersecretion.

    PubMed

    Zhou, Cuiqi; Jiao, Yonghui; Wang, Renzhi; Ren, Song-Guang; Wawrowsky, Kolja; Melmed, Shlomo

    2015-04-01

    Pituitary somatotroph adenomas result in dysregulated growth hormone (GH) hypersecretion and acromegaly; however, regulatory mechanisms that promote GH hypersecretion remain elusive. Here, we provide evidence that STAT3 directly induces somatotroph tumor cell GH. Evaluation of pituitary tumors revealed that STAT3 expression was enhanced in human GH-secreting adenomas compared with that in nonsecreting pituitary tumors. Moreover, STAT3 and GH expression were concordant in a somatotroph adenoma tissue array. Promoter and expression analysis in a GH-secreting rat cell line (GH3) revealed that STAT3 specifically binds the Gh promoter and induces transcription. Stable expression of STAT3 in GH3 cells induced expression of endogenous GH, and expression of a constitutively active STAT3 further enhanced GH production. Conversely, expression of dominant-negative STAT3 abrogated GH expression. In primary human somatotroph adenoma-derived cell cultures, STAT3 suppression with the specific inhibitor S3I-201 attenuated GH transcription and reduced GH secretion in the majority of derivative cultures. In addition, S3I-201 attenuated somatotroph tumor growth and GH secretion in a rat xenograft model. GH induced STAT3 phosphorylation and nuclear translocation, indicating a positive feedback loop between STAT3 and GH in somatotroph tumor cells. Together, these results indicate that adenoma GH hypersecretion is the result of STAT3-dependent GH induction, which in turn promotes STAT3 expression, and suggest STAT3 as a potential therapeutic target for pituitary somatotroph adenomas.

  16. Two domains of the V protein of virulent canine distemper virus selectively inhibit STAT1 and STAT2 nuclear import.

    PubMed

    Röthlisberger, Anne; Wiener, Dominique; Schweizer, Matthias; Peterhans, Ernst; Zurbriggen, Andreas; Plattet, Philippe

    2010-07-01

    Canine distemper virus (CDV) causes in dogs a severe systemic infection, with a high frequency of demyelinating encephalitis. Among the six genes transcribed by CDV, the P gene encodes the polymerase cofactor protein (P) as well as two additional nonstructural proteins, C and V; of these V was shown to act as a virulence factor. We investigated the molecular mechanisms by which the P gene products of the neurovirulent CDV A75/17 strain disrupt type I interferon (IFN-alpha/beta)-induced signaling that results in the establishment of the antiviral state. Using recombinant knockout A75/17 viruses, the V protein was identified as the main antagonist of IFN-alpha/beta-mediated signaling. Importantly, immunofluorescence analysis illustrated that the inhibition of IFN-alpha/beta-mediated signaling correlated with impaired STAT1/STAT2 nuclear import, whereas the phosphorylation state of these proteins was not affected. Coimmunoprecipitation assays identified the N-terminal region of V (VNT) responsible for STAT1 targeting, which correlated with its ability to inhibit the activity of the IFN-alpha/beta-mediated antiviral state. Conversely, while the C-terminal domain of V (VCT) could not function autonomously, when fused to VNT it optimally interacted with STAT2 and subsequently efficiently suppressed the IFN-alpha/beta-mediated signaling pathway. The latter result was further supported by a single mutation at position 110 within the VNT domain of CDV V protein, resulting in a mutant that lost STAT1 binding while retaining a partial STAT2 association. Taken together, our results identified the CDV VNT and VCT as two essential modules that complement each other to interfere with the antiviral state induced by IFN-alpha/beta-mediated signaling. Hence, our experiments reveal a novel mechanism of IFN-alpha/beta evasion among the morbilliviruses.

  17. Elevated interleukin-27 levels in human neonatal macrophages regulate indoleamine dioxygenase in a STAT-1 and STAT-3-dependent manner.

    PubMed

    Jung, Joo-Yong; Gleave Parson, Madeline; Kraft, Jennifer D; Lyda, Logan; Kobe, Brianna; Davis, Celestia; Robinson, Jembber; Peña, Maria Marjorette O; Robinson, Cory M

    2016-09-01

    Microbial infections are a major cause of infant mortality as a result of limitations in immune defences. Interleukin-27 (IL-27) is a heterodimeric cytokine produced primarily by leucocytes and is immunosuppressive toward lymphocytes and leucocytes. Our laboratory demonstrated that human neonatal macrophages express IL-27 more abundantly than adult macrophages. Similarly in mice, IL-27 expression is elevated early in life and maintained through infancy. To determine IL-27-regulated mechanisms that may limit immunity, we evaluated the expression of a number of genes in response to this cytokine in primary human neonatal macrophages. Indoleamine 2,3-dioxygenase (IDO) gene expression was increased dose-responsively by IL-27. We have previously demonstrated inhibition of T-cell proliferation and cytokine production by neonatal macrophage-generated IL-27, and IDO is often implicated in this negative regulation. An increase in IDO protein was demonstrated by immunofluorescence microscopy and was consistent with increased enzyme activity following treatment with IL-27. Inclusion of a soluble receptor to neutralize endogenous IL-27, decreased IDO expression and activity compared with untreated macrophages. In response to IL-27, neonatal macrophages phosphorylate signal transdcuer and activator of transcription 1 (STAT-1) and STAT-3. Both transcription factors are recruited to the IDO regulatory region. STAT-3 dominates during steady-state regulation by lower levels of endogenous IL-27 production. A shift to enhanced STAT-1 recruitment occurs during increased levels of exogenously supplied IL-27. These data suggest an interesting interplay of STAT-1 and STAT-3 to regulate IDO activity and immunosuppression in response to different levels of IL-27 in the microenvironment of the immune response that may further our understanding of this interesting cytokine.

  18. Comment on 'Nonlinear properties of small amplitude dust ion acoustic solitary waves' [Phys. Plasmas 7, 3594 (2000)

    SciTech Connect

    Duha, S. S.; Mamun, A. A.

    2008-10-15

    The aim of this comment is to show how the model equations used by Ghosh et al. [Phys. Plasmas 7, 3594 (2000)] are completely inconsistent, and to provide a guideline for a consistent dusty plasma model which is appropriate for the study of the nonlinear properties of the dust ion acoustic solitary waves.

  19. Erratum: “Hamiltonian magnetohydrodynamics: Lagrangian, Eulerian, and dynamically accessible stability—Theory” [Phys. Plasmas 20, 092104 (2013)

    SciTech Connect

    Andreussi, T.; Morrison, P. J.; Pegoraro, F.

    2015-03-15

    An algebraic mistake in the rendering of the Energy Casimir stability condition for a symmetric magnetohydrodynamics plasma configuration with flows made in the article Andreussi et al. “Hamiltonian magnetohydrodynamics: Lagrangian, Eulerian, and dynamically accessible stability—Theory,” Phys. Plasmas 20, 092104 (2013) is corrected.

  20. Response to 'Comment on 'Nonlinear properties of small amplitude dust ion acoustic solitary waves'' [Phys. Plasmas 15, 104703 (2008)

    SciTech Connect

    Gupta, M. R.; Sarkar, S.; Khan, Manoranjan; Ghosh, Samiran

    2008-10-15

    The objections are not justified. It should have been noted that ion charge number z{sub i}=1 throughout the referred paper [Ghosh et al., Phys. Plasmas 7, 3594 (2000)]. There is no inconsistency in the formulation of the referred paper as explained in the text.

  1. Comments on ''theory of dissipative density-gradient-driven turbulence in the tokamak edge'' (Phys. Fluids 28, 1419 (1985))

    SciTech Connect

    Krommes, J.A.

    1985-11-01

    The author critiques the model of tokamak edge turbulence by P.W. Terry and P.H. Diamond (Phys. Fluids 28, 1419, 1985). The critique includes a discussion of the physical basis, consistency and quantitative accuracy of the Terry-Diamond model. 19 refs. (WRF)

  2. Comment on "On the Crooks fluctuation theorem and the Jarzynski equality" [J. Chem. Phys. 129, 091101 (2008)].

    PubMed

    Adib, Artur B

    2009-06-28

    It has recently been argued that a self-consistency condition involving the Jarzynski equality (JE) and the Crooks fluctuation theorem (CFT) is violated for a simple Brownian process [L. Y. Chen, J. Chem. Phys.129, 091101 (2008)]. This note adopts the definitions in the original formulation of the JE and CFT and demonstrates the contrary.

  3. Comment on "Soret motion in non-ionic binary molecular mixtures" [J. Chem. Phys. 135, 054102 (2011)].

    PubMed

    Semenov, Semen N; Schimpf, Martin E

    2012-09-28

    The material transport equations derived in the article by Leroyer and Würger [J. Chem. Phys. 135, 054102 (2011)] do not adequately provide a description of material transport in liquid binary systems. An alternate approach based on non-equilibrium thermodynamics is presented.

  4. Comment on 'Energy transfer in nanowire solar cells with photon-harvesting shells' [J. Appl. Phys. 105, 124509 (2009)

    SciTech Connect

    Markvart, T.; Danos, L.; Greef, R.

    2010-07-15

    In a recent article, Peters et al. [J. Appl. Phys. 105, 124509 (2009)] claim to have observed photosensitization of crystalline silicon by energy transfer from an optically absorbing thin polymer film. We show that this claim is not justified. Their experimental design is not adequate to establish enhanced photoexcitation of silicon; moreover, the theoretical arguments in their interpretation do not stand up to scrutiny.

  5. Opportunity's Surroundings on Sol 1818 (Vertical)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,818th Martian day, or sol, of Opportunity's surface mission (March 5, 2009). South is at the center; north at both ends.

    This view is presented as a vertical projection with geometric seam correction. North is at the top.

    The rover had driven 80.3 meters (263 feet) southward earlier on that sol. Tracks from the drive recede northward in this view.

    The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock.

  6. Opportunity's Surroundings After Sol 1820 Drive

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,820th to 1,822nd Martian days, or sols, of Opportunity's surface mission (March 7 to 9, 2009). South is at the center; north at both ends.

    The rover had driven 20.6 meters toward the northwest on Sol 1820 before beginning to take the frames in this view. Tracks from that drive recede southwestward. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches).

    The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and small exposures of lighter-toned bedrock.

    This view is presented as a cylindrical projection with geometric seam correction.

  7. Opportunity's Surroundings on Sol 1798 (Vertical)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this 180-degree view of the rover's surroundings during the 1,798th Martian day, or sol, of Opportunity's surface mission (Feb. 13, 2009). North is on top.

    This view is presented as a vertical projection with geometric seam correction.

    The rover had driven 111 meters (364 feet) southward on the preceding sol. Tracks from that drive recede northward in this view. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches).

    The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock.

  8. Opportunity's Surroundings After Sol 1820 Drive (Polar)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,820th to 1,822nd Martian days, or sols, of Opportunity's surface mission (March 7 to 9, 2009).

    This view is presented as a polar projection with geometric seam correction. North is at the top.

    The rover had driven 20.6 meters toward the northwest on Sol 1820 before beginning to take the frames in this view. Tracks from that drive recede southwestward. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches).

    The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and small exposures of lighter-toned bedrock.

  9. Opportunity's Surroundings After Sol 1820 Drive (Vertical)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,820th to 1,822nd Martian days, or sols, of Opportunity's surface mission (March 7 to 9, 2009).

    This view is presented as a vertical projection with geometric seam correction. North is at the top.

    The rover had driven 20.6 meters toward the northwest on Sol 1820 before beginning to take the frames in this view. Tracks from that drive recede southwestward. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches).

    The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and small exposures of lighter-toned bedrock.

  10. Opportunity's Surroundings on Sol 1818 (Polar)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,818th Martian day, or sol, of Opportunity's surface mission (March 5, 2009). South is at the center; north at both ends.

    This view is presented as a polar projection with geometric seam correction. North is at the top.

    The rover had driven 80.3 meters (263 feet) southward earlier on that sol. Tracks from the drive recede northward in this view.

    The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock.

  11. Opportunity's Surroundings on Sol 1798 (Polar)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this 180-degree view of the rover's surroundings during the 1,798th Martian day, or sol, of Opportunity's surface mission (Feb. 13, 2009). North is on top.

    This view is presented as a polar projection with geometric seam correction.

    The rover had driven 111 meters (364 feet) southward on the preceding sol. Tracks from that drive recede northward in this view. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches).

    The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock.

  12. Phoenix Robotic Arm's Workspace After 90 Sols

    NASA Technical Reports Server (NTRS)

    2008-01-01

    During the first 90 Martian days, or sols, after its May 25, 2008, landing on an arctic plain of Mars, NASA's Phoenix Mars Lander dug several trenches in the workspace reachable with the lander's robotic arm.

    The lander's Surface Stereo Imager camera recorded this view of the workspace on Sol 90, early afternoon local Mars time (overnight Aug. 25 to Aug. 26, 2008). The shadow of the the camera itself, atop its mast, is just left of the center of the image and roughly a third of a meter (one foot) wide.

    The workspace is on the north side of the lander. The trench just to the right of center is called 'Neverland.'

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  13. Impediment to Spirit Drive on Sol 1806

    NASA Technical Reports Server (NTRS)

    2009-01-01

    The hazard avoidance camera on the front of NASA's Mars Exploration Rover Spirit took this image after a drive by Spirit on the 1,806th Martian day, or sol, (January 31, 2009) of Spirit's mission on the surface of Mars.

    The wheel at the bottom right of the image is Spirit's right-front wheel. Because that wheel no longer turns, Spirit drives backwards dragging that wheel. The drive on Sol 1806 covered about 30 centimeters (1 foot). The rover team had planned a longer drive, but Spirit stopped short, apparently from the right front wheel encountering the partially buried rock visible next to that wheel.

    The hazard avoidance cameras on the front and back of the rover provide wide-angle views. The hill on the horizon in the right half of this image is Husband Hill. Spirit reached the summit of Husband Hill in 2005.

  14. Innovative materials based on sol gel technology

    NASA Astrophysics Data System (ADS)

    Reisfeld, Renata; Saraidarov, Tsiala

    2006-01-01

    We review the sol-gel based new materials which were prepared in our laboratory including: tunable lasers, active waveguides, luminescent solar concentrators, electrochromic, photochromic and gasochromic plates for smart windows, chemical and biological sensors, semiconductor quantum dots and complexes of rare earth ions. In this paper we present the firstly obtained results of the Eu sulfide nanocrystalline (NCs) powder material and doped in the sol-gel based zirconia films. The powder and films were studied by high resolution transmittance electron microscopy (HRTEM), energy dispersive X-ray spectroscopy analysis (EDS) and luminescence spectroscopy. Eu sulfide nanocrystals (NCs) ranging between 8 and 10 nm were obtained as powder and 3-4 nm incorporated in zirconia film.

  15. Droplet Spreading with Sol-Gel Transition

    NASA Astrophysics Data System (ADS)

    Jalaal, Maziyar; Stoeber, Boris; Balmforth, Neil J.

    2014-11-01

    The impact and spreading of liquid droplets on a smooth solid substrate is a classical subject with several industrial applications such as ink-jet printing, spray cooling, coating, and many others. For many of these deposition processes, controlling the final shape of the drop is critical. In the current research, a new technique for controlling the spreading of droplets impacting a substrate is presented. This technique exploits the rheology of a thermo-responsive polymer solution that undergoes a reversible sol/gel transition above a critical temperature. Experiments are conducted using a combination of shadowgraphy and micro-PIV to observe spreading drops. It is shown that the final diameter of a droplet can be controlled through the temperature of the substrate and the tunable sol/gel transition temperature of the fluid.A mathematical model is provided to further elucidate the flow dynamics.

  16. PASD1 promotes STAT3 activity and tumor growth by inhibiting TC45-mediated dephosphorylation of STAT3 in the nucleus.

    PubMed

    Xu, Zhi-Sheng; Zhang, Hong-Xia; Zhang, Yu-Long; Liu, Tian-Tian; Ran, Yong; Chen, Liu-Ting; Wang, Yan-Yi; Shu, Hong-Bing

    2016-06-01

    Activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) is tightly regulated during various physiological processes, such as cell proliferation, survival, and differentiation, and aberrant STAT3 activation results in tumorigenesis. In this study, we identified the cancer/testis antigen PASD1 as a positive regulator of STAT3 activity. Overexpression of PASD1 activated STAT3 and potentiated IL-6-induced activation of STAT3, whereas knockdown of PASD1 had opposite effects. Endogenous coimmunoprecipitation experiments indicated that PASD1 interacted with STAT3 in the nucleus. Overexpression of PASD1 enhanced both basal and IL-6-induced STAT3 phosphorylation at Y705, whereas knockdown of PASD1 had opposite effects. Mechanistically, PASD1 competed with TC45, a nuclear protein tyrosine phosphatase, to associate with STAT3, thus inhibited TC45-mediated dephosphorylation of STAT3. Consistently, knockdown of PASD1 inhibited expression of many pro-oncogenic genes, leading to suppression of cell proliferation, anchorage-independent growth, cell migration, and tumor growth in nude mice. Our findings demonstrate that PASD1 serves as a critical nuclear positive regulator of STAT3-mediated gene expression and tumorigenesis.

  17. Analysis of STAT1 expression and biological activity reveals interferon-tau-dependent STAT1-regulated SOCS genes in the bovine endometrium.

    PubMed

    Vitorino Carvalho, A; Eozenou, C; Healey, G D; Forde, N; Reinaud, P; Chebrout, M; Gall, L; Rodde, N; Padilla, A Lesage; Delville, C Giraud; Leveugle, M; Richard, C; Sheldon, I M; Lonergan, P; Jolivet, G; Sandra, O

    2016-03-01

    Signal transducer and activator of transcription (STAT) proteins are critical for the regulation of numerous biological processes. In cattle, microarray analyses identified STAT1 as a differentially expressed gene in the endometrium during the peri-implantation period. To gain new insights about STAT1 during the oestrous cycle and early pregnancy, we investigated STAT1 transcript and protein expression, as well as its biological activity in bovine tissue and cells of endometrial origin. Pregnancy increased STAT1 expression on Day 16, and protein and phosphorylation levels on Day 20. In cyclic and pregnant females, STAT1 was located in endometrial cells but not in the luminal epithelium at Day 20 of pregnancy. The expression of STAT1 during the oestrous cycle was not affected by progesterone supplementation. In vivo and in vitro, interferon-tau (IFNT) stimulated STAT1 mRNA expression, protein tyrosine phosphorylation and nuclear translocation. Using chromatin immunoprecipitation in IFNT-stimulated endometrial cells, we demonstrated an increase of STAT1 binding on interferon regulatory factor 1 (IRF1), cytokine-inducible SH2-containing protein (CISH), suppressor of cytokine signaling 1 and 3 (SOCS1, SOCS3) gene promoters consistent with the induction of their transcripts. Our data provide novel molecular insights into the biological functions of STAT1 in the various cells composing the endometrium during maternal pregnancy recognition and implantation.

  18. STAT3 phosphorylation in injured axons before sensory and motor neuron nuclei: potential role for STAT3 as a retrograde signaling transcription factor.

    PubMed

    Lee, Nancy; Neitzel, Karen L; Devlin, Brenda K; MacLennan, A John

    2004-07-05

    STAT3 is a latent transcription factor that is activated by plasma membrane growth factor receptor complexes. Conditional gene disruption data indicate that it contributes to the survival of cranial motor neurons after peripheral nerve lesion. In agreement, levels of activated STAT3 (Tyr705-phosphorylated STAT3) have been shown to increase in the nuclei of adult cranial motor neurons during their regeneration after the same injury. The data presented here demonstrate that STAT3 is similarly but not identically affected in sciatic motor neurons after sciatic nerve injury. In addition, we find that sensory neuron nuclei also display an analogous increase in activated STAT3, thereby supporting a role for STAT3 in the survival and regeneration of these cells. Most interesting, the present data indicate that peripheral nerve lesion leads to a very rapid activation of STAT3 in axons at the lesion site. This response increases during the first 24 hours after injury and extends back to the motor and sensory neurons such that phospho-STAT3-immunoreactive axons are first detected in the dorsal root ganglia and ventral spinal cord at the same postlesion time intervals at which the activated STAT3 is first detected in the neuronal nuclei. Together these data raise the possibility that axonal STAT3, activated at the injury site, acts as a retrograde signaling transcription factor, which promotes the survival and regeneration of both sensory and motor neurons.

  19. Differential contributions of STAT5A and STAT5B to stress protection and tyrosine kinase inhibitor resistance of chronic myeloid leukemia stem/progenitor cells.

    PubMed

    Casetti, Luana; Martin-Lannerée, Séverine; Najjar, Imen; Plo, Isabelle; Augé, Sylvie; Roy, Lydia; Chomel, Jean-Claude; Lauret, Evelyne; Turhan, Ali G; Dusanter-Fourt, Isabelle

    2013-04-01

    STAT5 fulfills essential roles in hematopoietic stem cell (HSC) self-renewal and chronic myeloid leukemia (CML), a prototypical stem cell malignancy. However, the specific contributions of the two related genes STAT5A and STAT5B have not been determined. In this study, we used a RNAi-based strategy to establish participation of these genes to CML disease and persistence following targeted therapy. We showed that STAT5A/STAT5B double-knockdown triggers CML cell apoptosis and suppresses both normal and CML HSC long-term clonogenic potential. STAT5A and STAT5B exhibited similar prosurvival activity, but STAT5A attenuation alone was ineffective at impairing growth of normal and CML CD34(+) cells isolated at diagnosis. In contrast, STAT5A attenuation was sufficient to enhance basal oxidative stress and DNA damage of normal CD34(+) and CML cells. Furthermore, it weakened the ability to manage exogenous oxidative stress, increased p53 (TRP53)/CHK-2 (CHEK2) stress pathway activation, and enhanced prolyl hydroxylase domain (PHD)-3 (EGLN3) mRNA expression. Only STAT5A and its transactivation domain-deficient mutant STAT5AΔ749 specifically rescued these activities. STAT5A attenuation was also active at inhibiting growth of CML CD34(+) cells from patients with acquired resistance to imatinib. Our findings show that STAT5A has a selective role in contributing to stress resistance through unconventional mechanisms, offering new opportunities to eradicate the most primitive and tyrosine kinase inhibitor-resistant CML cells with an additional potential to eradicate persistent stem cell populations.

  20. Ring-Resonator/Sol-Gel Interferometric Immunosensor

    NASA Technical Reports Server (NTRS)

    Bearman, Gregory; Cohen, David

    2007-01-01

    A proposed biosensing system would be based on a combination of (1) a sensing volume containing antibodies immobilized in a sol-gel matrix and (2) an optical interferometer having a ring resonator configuration. The antibodies would be specific to an antigen species that one seeks to detect. In the ring resonator of the proposed system, light would make multiple passes through the sensing volume, affording greater interaction length and, hence, greater antibody- detection sensitivity.

  1. Spirit Near 'Stapledon' on Sol 1802 (Vertical)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA Mars Exploration Rover Spirit used its navigation camera for the images assembled into this full-circle view of the rover's surroundings during the 1,802nd Martian day, or sol, (January 26, 2009) of Spirit's mission on the surface of Mars. North is at the top.

    This view is presented as a vertical projection with geometric seam correction.

    Spirit had driven down off the low plateau called 'Home Plate' on Sol 1782 (January 6, 2009) after spending 12 months on a north-facing slope on the northern edge of Home Plate. The position on the slope (at about the 9-o'clock position in this view) tilted Spirit's solar panels toward the sun, enabling the rover to generate enough electricity to survive its third Martian winter. Tracks at about the 11-o'clock position of this panorama can be seen leading back to that 'Winter Haven 3' site from the Sol 1802 position about 10 meters (33 feet) away. For scale, the distance between the parallel wheel tracks is about one meter (40 inches).

    Where the receding tracks bend to the left, a circular pattern resulted from Spirit turning in place at a soil target informally named 'Stapledon' after William Olaf Stapledon, a British philosopher and science-fiction author who lived from 1886 to 1950. Scientists on the rover team suspected that the soil in that area might have a high concentration of silica, resembling a high-silica soil patch discovered east of Home Plate in 2007. Bright material visible in the track furthest to the right was examined with Spirit's alpha partical X-ray spectrometer and found, indeed, to be rich in silica.

    The team laid plans to drive Spirit from this Sol 1802 location back up onto Home Plate, then southward for the rover's summer field season.

  2. Spirit Near 'Stapledon' on Sol 1802 (Polar)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA Mars Exploration Rover Spirit used its navigation camera for the images assembled into this full-circle view of the rover's surroundings during the 1,802nd Martian day, or sol, (January 26, 2009) of Spirit's mission on the surface of Mars. North is at the top.

    This view is presented as a polar projection with geometric seam correction.

    Spirit had driven down off the low plateau called 'Home Plate' on Sol 1782 (January 6, 2009) after spending 12 months on a north-facing slope on the northern edge of Home Plate. The position on the slope (at about the 9-o'clock position in this view) tilted Spirit's solar panels toward the sun, enabling the rover to generate enough electricity to survive its third Martian winter. Tracks at about the 11-o'clock position of this panorama can be seen leading back to that 'Winter Haven 3' site from the Sol 1802 position about 10 meters (33 feet) away. For scale, the distance between the parallel wheel tracks is about one meter (40 inches).

    Where the receding tracks bend to the left, a circular pattern resulted from Spirit turning in place at a soil target informally named 'Stapledon' after William Olaf Stapledon, a British philosopher and science-fiction author who lived from 1886 to 1950. Scientists on the rover team suspected that the soil in that area might have a high concentration of silica, resembling a high-silica soil patch discovered east of Home Plate in 2007. Bright material visible in the track furthest to the right was examined with Spirit's alpha partical X-ray spectrometer and found, indeed, to be rich in silica.

    The team laid plans to drive Spirit from this Sol 1802 location back up onto Home Plate, then southward for the rover's summer field season.

  3. Spirit Near 'Stapledon' on Sol 1802

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA Mars Exploration Rover Spirit used its navigation camera for the images assembled into this full-circle view of the rover's surroundings during the 1,802nd Martian day, or sol, (January 26, 2009) of Spirit's mission on the surface of Mars. South is at the center; north is at both ends.

    Spirit had driven down off the low plateau called 'Home Plate' on Sol 1782 (January 6, 2009) after spending 12 months on a north-facing slope on the northern edge of Home Plate. The position on the slope (at about the 9-o'clock position in this view) tilted Spirit's solar panels toward the sun, enabling the rover to generate enough electricity to survive its third Martian winter. Tracks at about the 11-o'clock position of this panorama can be seen leading back to that 'Winter Haven 3' site from the Sol 1802 position about 10 meters (33 feet) away. For scale, the distance between the parallel wheel tracks is about one meter (40 inches).

    Where the receding tracks bend to the left, a circular pattern resulted from Spirit turning in place at a soil target informally named 'Stapledon' after William Olaf Stapledon, a British philosopher and science-fiction author who lived from 1886 to 1950. Scientists on the rover team suspected that the soil in that area might have a high concentration of silica, resembling a high-silica soil patch discovered east of Home Plate in 2007. Bright material visible in the track furthest to the right was examined with Spirit's alpha partical X-ray spectrometer and found, indeed, to be rich in silica.

    The team laid plans to drive Spirit from this Sol 1802 location back up onto Home Plate, then southward for the rover's summer field season.

    This view is presented as a cylindrical projection with geometric seam correction.

  4. Alkali cold gelation of whey proteins. Part I: sol-gel-sol(-gel) transitions.

    PubMed

    Mercadé-Prieto, Ruben; Gunasekaran, Sundaram

    2009-05-19

    The cold gelation of preheated whey protein isolate (WPI) solutions at alkaline conditions (pH>10) has been studied to better understand the effect of NaOH in the formation and destruction of whey protein aggregates and gels. Oscillatory rheology has been used to follow the gelation process, resulting in novel and different gelation profiles with the gelation pH. At low alkaline pH, typical sol-gel transitions are observed, as in many other biopolymers. At pH>11.5, the system gels quickly, after approximately 300 s, followed by a slow degelation step that transforms the gel to a viscous solution. Finally, there is a second gelation step. This results in a surprising sol-gel-sol-gel transition in time at constant gelation conditions. At very high pH (>12.5), the degelation step is very severe, and the second gelation step is not observed, resulting in a sol-gel-sol transition. The first quick gelation step is related to the quick swelling of the WPI aggregates in alkali, as observed from light scattering, which enables the formation of new noncovalent interactions to form a gel network. These interactions are argued to be destroyed in the subsequent degelation step. Disulfide cross-linking is observed only in the second gelation step, not in the first step.

  5. Fun with SFX and stat_object_offline.

    SciTech Connect

    Ou, Carol

    2012-04-01

    SFX's built-in statistical reports can be handy, but sometimes you might want to slice and dice SFX statistics a little more closely than those reports allow. This session will discuss some preliminary efforts to use the data in SFX's stat{_}object{_}offline table to learn more about our users and how they use SFX.

  6. Predicting Mobility using Statistics (PreMoStat)

    DTIC Science & Technology

    2011-03-10

    Fixture Gantry for Swapping Curbs Motion Capture Alternate Curb M bl Camera Landing Platform Sand/Soil PackBot ova e Curb Bin Sand Smoothing...multiple functions. • Function computing normal forces • Function compute shear forces PreMoStat_GFOSUB.f • Function terrain query • Function error

  7. Essential role of Stat6 in IL-4 signalling.

    PubMed

    Takeda, K; Tanaka, T; Shi, W; Matsumoto, M; Minami, M; Kashiwamura, S; Nakanishi, K; Yoshida, N; Kishimoto, T; Akira, S

    1996-04-18

    Interleukin-4 (IL-4) is a pleiotropic lymphokine which plays an important role in the immune system. IL-4 activates two distinct signalling pathways through tyrosine phosphorylation of Stat6, a signal transducer and activator of transcription, and of a 170K protein called 4PS. To investigate the functional role of Stat6 in IL-4 signalling, we generated mice deficient in Stat6 by gene targeting. We report here that in the mutant mice, expression of CD23 and major histocompatibility complex (MHC) class II in resting B cells was not enhanced in response to IL-4. IL-4 induced B-cell proliferation costimulated by anti-IgM antibody was abolished. The T-cell proliferative response was also notably reduced. Furthermore, production of Th2 cytokines from T cells as well as IgE and IgG1 responses after nematode infection were profoundly reduced. These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses.

  8. 2-Guanidinoquinazolines as new inhibitors of the STAT3 pathway

    PubMed Central

    LaPorte, Matthew G.; da Paz Lima, Dimas José; Zhang, Feng; Sen, Malabika; Grandis, Jennifer R.; Camarco, Daniel; Hua, Yun; Johnston, Paul A.; Lazo, John S.; Resnick, Lynn O.; Wipf, Peter; Huryn, Donna M.

    2014-01-01

    Synthesis and SAR investigation of 2-guanidinoquinazolines, initially identified in a high content screen for selective STAT3 pathway inhibitors, led to a more potent analog (11c) that demonstrated improved anti-proliferative activity against a panel of HNSCC cell lines. PMID:25288188

  9. Pancreatic STAT3 protects mice against caerulein-induced pancreatitis via PAP1 induction.

    PubMed

    Shigekawa, Minoru; Hikita, Hayato; Kodama, Takahiro; Shimizu, Satoshi; Li, Wei; Uemura, Akio; Miyagi, Takuya; Hosui, Atsushi; Kanto, Tatsuya; Hiramatsu, Naoki; Tatsumi, Tomohide; Takeda, Kiyoshi; Akira, Shizuo; Takehara, Tetsuo

    2012-12-01

    The signal transducer and activator of transcription 3 (STAT3) is a transcription factor that controls expressions of several genes involved in cell survival, proliferation and differentiation, and tissue inflammation. However, the significance of pancreatic STAT3 in acute pancreatitis remains unclear. We generated conditional STAT3 knockout (stat3(Δ/Δ)) mice by crossing stat3(flox/flox) mice with Pdx1-promoter Cre transgenic mice. Caerulein administration activated pancreatic STAT3 and induced acute pancreatitis as early as 3 hours in wild-type mice, and full recovery from the induced pancreatic injury was observed within 7 days. The levels of serum amylase and lipase and histologic scores of pancreatic necrosis and inflammatory cell infiltration were significantly higher at 3 hours in stat3(Δ/Δ) mice than in stat3(flox/flox) mice. Pancreatic recovery after pancreatitis was significantly delayed in stat3(Δ/Δ) mice compared with stat3(flox/flox) mice. Although stat3(flox/flox) mice had marked production in the pancreas of pancreatitis-associated protein 1 (PAP1), a serum acute phase protein, this induction was completely abrogated in stat3(Δ/Δ) mice. Enforced production of PAP1 by a hydrodynamic procedure in the liver significantly suppressed pancreatic necrosis and inflammation and also promoted pancreatic regeneration and recovery in stat3(Δ/Δ) mice to levels similar to those observed in stat3(flox/flox) mice. In conclusion, pancreatic STAT3 is indispensable for PAP1 production, and this STAT3/PAP1 pathway plays a protective role in caerulein-induced pancreatitis.

  10. Targeted inhibition of STATs and IRFs as a potential treatment strategy in cardiovascular disease

    PubMed Central

    Szelag, Malgorzata; Piaszyk-Borychowska, Anna; Plens-Galaska, Martyna; Wesoly, Joanna; Bluyssen, Hans A.R.

    2016-01-01

    Key factors contributing to early stages of atherosclerosis and plaque development include the pro-inflammatory cytokines Interferon (IFN)α, IFNγ and Interleukin (IL)-6 and Toll-like receptor 4 (TLR4) stimuli. Together, they trigger activation of Signal Transducer and Activator of Transcription (STAT) and Interferon Regulatory Factor (IRF) families. In particular, STAT1, 2 and 3; IRF1 and 8 have recently been recognized as prominent modulators of inflammation, especially in immune and vascular cells during atherosclerosis. Moreover, inflammation-mediated activation of these STATs and IRFs coordinates a platform for synergistic amplification leading to pro-atherogenic responses. Searches for STAT3-targeting compounds, exploring the pTyr-SH2 interaction area of STAT3, yielded many small molecules including natural products. Only a few inhibitors for other STATs, but none for IRFs, are described. Promising results for several STAT3 inhibitors in recent clinical trials predicts STAT3-inhibiting strategies may find their way to the clinic. However, many of these inhibitors do not seem STAT-specific, display toxicity and are not very potent. This illustrates the need for better models, and screening and validation tools for novel STAT and IRF inhibitors. This review presents a summary of these findings. It postulates STAT1, STAT2 and STAT3 and IRF1 and IRF8 as interesting therapeutic targets and targeted inhibition could be a potential treatment strategy in CVDs. In addition, it proposes a pipeline approach that combines comparative in silico docking of STAT-SH2 and IRF-DBD models with in vitro STAT and IRF activation inhibition validation, as a novel tool to screen multi-million compound libraries and identify specific inhibitors for STATs and IRFs. PMID:27166190

  11. Opportunity's Surroundings on Sol 1687 (Stereo)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    [figure removed for brevity, see original site] Left-eye view of a color stereo pair for PIA11739 [figure removed for brevity, see original site] Right-eye view of a color stereo pair for PIA11739

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this stereo, 360-degree view of the rover's surroundings on the 1,687th Martian day, or sol, of its surface mission (Oct. 22, 2008). The view appears three-dimensional when viewed through red-blue glasses.

    Opportunity had driven 133 meters (436 feet) that sol, crossing sand ripples up to about 10 centimeters (4 inches) tall. The tracks visible in the foreground are in the east-northeast direction.

    Opportunity's position on Sol 1687 was about 300 meters southwest of Victoria Crater. The rover was beginning a long trek toward a much larger crater, Endeavour, about 12 kilometers (7 miles) to the southeast.

    This panorama combines right-eye and left-eye views presented as cylindrical-perspective projections with geometric seam correction.

  12. Sol-Gel Manufactured Energetic Materials

    DOEpatents

    Simpson, Randall L.; Lee, Ronald S.; Tillotson, Thomas M.; Hrubesh, Lawrence W.; Swansiger, Rosalind W.; Fox, Glenn A.

    2005-05-17

    Sol-gel chemistry is used for the preparation of energetic materials (explosives, propellants and pyrotechnics) with improved homogeneity, and/or which can be cast to near-net shape, and/or made into precision molding powders. The sol-gel method is a synthetic chemical process where reactive monomers are mixed into a solution, polymerization occurs leading to a highly cross-linked three dimensional solid network resulting in a gel. The energetic materials can be incorporated during the formation of the solution or during the gel stage of the process. The composition, pore, and primary particle sizes, gel time, surface areas, and density may be tailored and controlled by the solution chemistry. The gel is then dried using supercritical extraction to produce a highly porous low density aerogel or by controlled slow evaporation to produce a xerogel. Applying stress during the extraction phase can result in high density materials. Thus, the sol-gel method can be used for precision detonator explosive manufacturing as well as producing precision explosives, propellants, and pyrotechnics, along with high power composite energetic materials.

  13. Sol-gel manufactured energetic materials

    DOEpatents

    Simpson, Randall L.; Lee, Ronald S.; Tillotson, Thomas M.; Hrubesh, Lawrence W.; Swansiger, Rosalind W.; Fox, Glenn A.

    2003-12-23

    Sol-gel chemistry is used for the preparation of energetic materials (explosives, propellants and pyrotechnics) with improved homogeneity, and/or which can be cast to near-net shape, and/or made into precision molding powders. The sol-gel method is a synthetic chemical process where reactive monomers are mixed into a solution, polymerization occurs leading to a highly cross-linked three dimensional solid network resulting in a gel. The energetic materials can be incorporated during the formation of the solution or during the gel stage of the process. The composition, pore, and primary particle sizes, gel time, surface areas, and density may be tailored and controlled by the solution chemistry. The gel is then dried using supercritical extraction to produce a highly porous low density aerogel or by controlled slow evaporation to produce a xerogel. Applying stress during the extraction phase can result in high density materials. Thus, the sol-gel method can be used for precision detonator explosive manufacturing as well as producing precision explosives, propellants, and pyrotechnics, along with high power composite energetic materials.

  14. Sol-gel based optical chemical sensors

    NASA Astrophysics Data System (ADS)

    Lobnik, Aleksandra; Korent Urek, Špela; Turel, Matejka; Frančič, Nina

    2011-05-01

    The growing activity in the field of optical chemical sensors has resulted in numerous sensing schemes, new indicator dyes, various polymeric matrix, size and shapes and highly diversified methods of immobilization. The sensor characteristics are dependent upon the choice of indicator, polymer, immobilization technique, and also size. Sol-gel technology provides a low-temperature method for obtaining porous silicate glass matrices. It enables to obtain material in the form of films, powders, monoliths, fibres or nanoparticles. Organic reagents and molecular receptors can be easily immobilized in the matrices. Moreover, one of the unique features of the sol-gel process is that the properties of the final network structure, such as hydrophobicity, thickness, porosity, flexibility, reactivity and stability can be easily tailored by controlling the process conditions, the type and the size of the precursors and catalysis. Here we will report about several sensor designed over the years based on sol-gel materials for monitoring and controlling different parameters, such as heavy metals, amines, phosphates, organophosphates.

  15. Heme Mediated STAT3 Activation in Severe Malaria

    PubMed Central

    Liu, Mingli; Amodu, Audu S.; Pitts, Sidney; Patrickson, John; Hibbert, Jacqueline M.; Battle, Monica; Ofori-Acquah, Solomon F.; Stiles, Jonathan K.

    2012-01-01

    Background The mortality of severe malaria [cerebral malaria (CM), severe malaria anemia (SMA), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)] remains high despite the availability associated with adequate treatments. Recent studies in our laboratory and others have revealed a hitherto unknown correlation between chemokine CXCL10/CXCR3, Heme/HO-1 and STAT3 and cerebral malaria severity and mortality. Although Heme/HO-1 and CXCL10/CXCR3 interactions are directly involved in the pathogenesis of CM and fatal disease, the mechanism dictating how Heme/HO-1 and CXCL10/CXCR3 are expressed and regulated under these conditions is still unknown. We therefore tested the hypothesis that these factors share common signaling pathways and may be mutually regulated. Methods We first clarified the roles of Heme/HO-1, CXCL10/CXCR3 and STAT3 in CM pathogenesis utilizing a well established experimental cerebral malaria mouse (ECM, P. berghei ANKA) model. Then, we further determined the mechanisms how STAT3 regulates HO-1 and CXCL10 as well as mutual regulation among them in CRL-2581, a murine endothelial cell line. Results The results demonstrate that (1) STAT3 is activated by P. berghei ANKA (PBA) infection in vivo and Heme in vitro. (2) Heme up-regulates HO-1 and CXCL10 production through STAT3 pathway, and regulates CXCL10 at the transcriptional level in vitro. (3) HO-1 transcription is positively regulated by CXCL10. (4) HO-1 regulates STAT3 signaling. Conclusion Our data indicate that Heme/HO-1, CXCL10/CXCR3 and STAT3 molecules as well as related signaling pathways play very important roles in the pathogenesis of severe malaria. We conclude that these factors are mutually regulated and provide new opportunities to develop potential novel therapeutic targets that could be used to supplement traditional prophylactics and treatments for malaria and improve clinical outcomes while reducing malaria mortality. Our ultimate goal is to develop novel therapies

  16. Methotrexate Is a JAK/STAT Pathway Inhibitor

    PubMed Central

    Thomas, Sally; Fisher, Katherine H.; Snowden, John A.; Danson, Sarah J.; Brown, Stephen; Zeidler, Martin P.

    2015-01-01

    Background The JAK/STAT pathway transduces signals from multiple cytokines and controls haematopoiesis, immunity and inflammation. In addition, pathological activation is seen in multiple malignancies including the myeloproliferative neoplasms (MPNs). Given this, drug development efforts have targeted the pathway with JAK inhibitors such as ruxolitinib. Although effective, high costs and side effects have limited its adoption. Thus, a need for effective low cost treatments remains. Methods & Findings We used the low-complexity Drosophila melanogaster pathway to screen for small molecules that modulate JAK/STAT signalling. This screen identified methotrexate and the closely related aminopterin as potent suppressors of STAT activation. We show that methotrexate suppresses human JAK/STAT signalling without affecting other phosphorylation-dependent pathways. Furthermore, methotrexate significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F, a mutation associated with most human MPNs. Methotrexate acts independently of dihydrofolate reductase (DHFR) and is comparable to the JAK1/2 inhibitor ruxolitinib. However, cells treated with methotrexate still retain their ability to respond to physiological levels of the ligand erythropoietin. Conclusions Aminopterin and methotrexate represent the first chemotherapy agents developed and act as competitive inhibitors of DHFR. Methotrexate is also widely used at low doses to treat inflammatory and immune-mediated conditions including rheumatoid arthritis. In this low-dose regime, folate supplements are given to mitigate side effects by bypassing the biochemical requirement for DHFR. Although independent of DHFR, the mechanism-of-action underlying the low-dose effects of methotrexate is unknown. Given that multiple pro-inflammatory cytokines signal through the pathway, we suggest that suppression of the JAK/STAT pathway is likely to be the principal anti-inflammatory and immunosuppressive mechanism-of-action of low

  17. STAT-3 inhibitors: state of the art and new horizons for cancer treatment.

    PubMed

    Lavecchia, A; Di Giovanni, C; Novellino, E

    2011-01-01

    The signal transducers and activators of transcription (STATs) include a class of cytoplasmic signaling proteins whose role in the regulation of cell growth and survival is mediated by phosphorylation of a critical tyrosine residue within the STAT protein. This occurs in response to cytokines and growth factors modulating the expression of specific target genes. In particular, phosphorylation induces STAT:STAT dimer formation between two monomers, via reciprocal phosphoTyr (pTyr)-SH2 domain interactions. To date, seven members of the STAT family, all with different roles, have been identified in mammals. After dimerization, phosphorylated STATs enter the nucleus and, working co-ordinately with other transcriptional co-activators and transcription factors, induce increased transcriptional initiation. In healthy human and animal cells, ligand-dependent activation of STATs is a transient process, lasting for several minutes to several hours. In contrast, in many cancerous cell lines and tumors, where growth factor dysregulation is frequently at the heart of cellular transformation, the STAT proteins (in particular STAT1, 3 and 5) are persistently tyrosine-phosphorylated or activated; abnormal levels of STAT3 activation have been observed in breast, ovarian, prostate, hematological and head and neck cancer cell lines. Thus, in this review, we examine the most important classes of agents designed to disrupt STAT3 signaling, with particular regard to STAT3 dimerization inhibitors, which could play a significant role in the future of cancer and adjuvant cancer therapies.

  18. Differences in antiproliferative effect of STAT3 inhibition in HCC cells with versus without HBV expression

    SciTech Connect

    Hong, Yun; Zhou, Lin; Xie, Haiyang; Wang, Weilin; Zheng, Shusen

    2015-06-05

    Chronic infection with hepatitis B virus (HBV) plays an important role in the etiology of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 3 (STAT3) inactivation could inhibit the tumor growth of HCC. In this study, differential antiproliferative effect of STAT3 inhibition was observed with HBV-related HCC cells being more resistant than non-HBV-related HCC cells. Resistance of HBV-related HCC cells to STAT3 inhibition was positively correlated to the expression of HBV. Enhanced ERK activation after STAT3 blockade was detected in HBV-related HCC cells but not in non-HBV-related HCC cells. Combined ERK and STAT3 inhibition eliminates the discrepancy between the two types of HCC cells. Moderate reduced HBV expression was found after STAT3 inhibition. These findings disclose a discrepancy in cellular response to STAT3 inhibition between non-HBV-related and HBV-related HCC cells and underscore the complexity of antiproliferative effect of STAT3 inactivation in HBV-related HCC cells. - Highlights: • HBV endows HCC cells with resistance to STAT3 inactivation on proliferation. • Abnormal ERK activation after STAT3 inhibition in HBV-related HCC cells. • Combined ERK and STAT3 inhibition eliminates the discrepancy. • STAT3 inhibition moderately reduces HBV expression.

  19. A Streamflow Statistics (StreamStats) Web Application for Ohio

    USGS Publications Warehouse

    Koltun, G.F.; Kula, Stephanie P.; Puskas, Barry M.

    2006-01-01

    A StreamStats Web application was developed for Ohio that implements equations for estimating a variety of streamflow statistics including the 2-, 5-, 10-, 25-, 50-, 100-, and 500-year peak streamflows, mean annual streamflow, mean monthly streamflows, harmonic mean streamflow, and 25th-, 50th-, and 75th-percentile streamflows. StreamStats is a Web-based geographic information system application designed to facilitate the estimation of streamflow statistics at ungaged locations on streams. StreamStats can also serve precomputed streamflow statistics determined from streamflow-gaging station data. The basic structure, use, and limitations of StreamStats are described in this report. To facilitate the level of automation required for Ohio's StreamStats application, the technique used by Koltun (2003)1 for computing main-channel slope was replaced with a new computationally robust technique. The new channel-slope characteristic, referred to as SL10-85, differed from the National Hydrography Data based channel slope values (SL) reported by Koltun (2003)1 by an average of -28.3 percent, with the median change being -13.2 percent. In spite of the differences, the two slope measures are strongly correlated. The change in channel slope values resulting from the change in computational method necessitated revision of the full-model equations for flood-peak discharges originally presented by Koltun (2003)1. Average standard errors of prediction for the revised full-model equations presented in this report increased by a small amount over those reported by Koltun (2003)1, with increases ranging from 0.7 to 0.9 percent. Mean percentage changes in the revised regression and weighted flood-frequency estimates relative to regression and weighted estimates reported by Koltun (2003)1 were small, ranging from -0.72 to -0.25 percent and -0.22 to 0.07 percent, respectively.

  20. STAT4-associated natural killer cell tolerance following liver transplantation

    PubMed Central

    Jamil, K M; Hydes, T J; Cheent, K S; Cassidy, S A; Traherne, J A; Jayaraman, J; Trowsdale, J; Alexander, G J; Little, A-M; McFarlane, H; Heneghan, M A; Purbhoo, M A; Khakoo, S I

    2017-01-01

    Objective Natural killer (NK) cells are important mediators of liver inflammation in chronic liver disease. The aim of this study was to investigate why liver transplants (LTs) are not rejected by NK cells in the absence of human leukocyte antigen (HLA) matching, and to identify a tolerogenic NK cell phenotype. Design Phenotypic and functional analyses on NK cells from 54 LT recipients were performed, and comparisons made with healthy controls. Further investigation was performed using gene expression analysis and donor:recipient HLA typing. Results NK cells from non-HCV LT recipients were hypofunctional, with reduced expression of NKp46 (p<0.05) and NKp30 (p<0.001), reduced cytotoxicity (p<0.001) and interferon (IFN)-γ secretion (p<0.025). There was no segregation of this effect with HLA-C, and these functional changes were not observed in individuals with HCV. Microarray and RT-qPCR analysis demonstrated downregulation of STAT4 in NK cells from LT recipients (p<0.0001). Changes in the expression levels of the transcription factors Helios (p=0.06) and Hobit (p=0.07), which control NKp46 and IFNγ expression, respectively, were also detected. Hypofunctionality of NK cells was associated with impaired STAT4 phosphorylation and downregulation of the STAT4 target microRNA-155. Conversely in HCV-LT NK cell tolerance was reversed, consistent with the more aggressive outcome of LT for HCV. Conclusions LT is associated with transcriptional and functional changes in NK cells, resulting in reduced activation. NK cell tolerance occurs upstream of major histocompatibility complex (MHC) class I mediated education, and is associated with deficient STAT4 phosphorylation. STAT4 therefore represents a potential therapeutic target to induce NK cell tolerance in liver disease. PMID:26887815

  1. Activation of the JAK/STAT pathway in Behcet's disease.

    PubMed

    Tulunay, A; Dozmorov, M G; Ture-Ozdemir, F; Yilmaz, V; Eksioglu-Demiralp, E; Alibaz-Oner, F; Ozen, G; Wren, J D; Saruhan-Direskeneli, G; Sawalha, A H; Direskeneli, H

    2015-03-01

    Th1/Th17-type T-cell responses are upregulated in Behcet's disease (BD). However, signaling pathways associated with this aberrant immune response are not clarified. Whole-genome microarray profiling was performed with human U133 (Plus 2.0) chips using messenger RNA of isolated CD14(+) monocytes and CD4(+) T cells from peripheral blood mononucleated cell (PBMC) in patients with BD (n = 9) and healthy controls (HCs) (n = 9). Flow cytometric analysis of unstimulated (US) and stimulated (phytohaemagglutinin) signal transducer and activator of transcription (STAT3) and pSTAT3 expressions of PBMCs were also analyzed (BD and HC, both n = 26). Janus family of kinase (JAK1) was observed to be upregulated in both CD14(+) monocytes (1.95-fold) and CD4(+) T lymphocytes (1.40-fold) of BD patients. Using canonical pathway enrichment analysis, JAK/STAT signaling was identified as activated in both CD14(+) monocytes (P = 9.55E-03) and in CD4(+) lymphocytes (P =8.13E-04) in BD. Interferon signaling was also prominent among upregulated genes in CD14(+) monocytes (P = 5.62E-05). Glucocorticoid receptor signaling and interleukin (IL-6) signaling were among the most enriched pathways in differentially expressed genes in CD14+ monocytes (P = 2.45E-09 and 1.00E-06, respectively). Basal US total STAT3 expression was significantly higher in BD (1.2 vs 3.45, P < 0.05). The JAK1/STAT3 signaling pathway is activated in BD, possibly through the activation of Th1/Th17-type cytokines such as IL-2, interferon (IFN-γ), IL-6, IL-17 and IL-23.

  2. Ionogel Electrolytes through Sol-Gel Processing

    NASA Astrophysics Data System (ADS)

    Horowitz, Ariel I.

    Electrical energy needs have intensified due to the ubiquity of personal electronics, the decarbonization of energy services through electrification, and the use of intermittent renewable energy sources. Despite developments in mechanical and thermal methods, electrochemical technologies are the most convenient and effective means of storing electrical energy. These technologies include both electrochemical cells, commonly called batteries, and electrochemical double-layer capacitors, or "supercapacitors", which store energy electrostatically. Both device types require an ion-conducting electrolyte. Current devices use solutions of complex salts in organic solvents, leading to both toxicity and flammability concerns. These drawbacks can be avoided by replacing conventional electrolytes with room-temperature molten salts, known as ionic liquids (ILs). ILs are non-volatile, non-flammable, and offer high conductivity and good electrochemical stability. Device mass can be reduced by combining ILs with a solid scaffold material to form an "ionogel," further improving performance metrics. In this work, sol-gel chemistry is explored as a means of forming ionogel electrolytes. Sol-gel chemistry is a solution-based, industrially-relevant, well-studied technique by which solids such as silica can be formed in situ. Previous works used a simple acid-catalyzed sol-gel reaction to create brittle, glassy ionogels. Here, both the range of products that can be accomplished through sol-gel processing and the understanding of interactions between ILs and the sol-gel reaction network are greatly expanded. This work introduces novel ionogel materials, including soft and compliant silica-supported ionogels and PDMS-supported ionogels. The impacts of the reactive formulation, IL identity, and casting time are detailed. It is demonstrated that variations in formulation can lead to rapid gelation and open pore structures in the silica scaffold or slow gelation and more dense silica

  3. Sol-gel processing to form doped sol-gel monoliths inside hollow core optical fiber and sol-gel core fiber devices made thereby

    NASA Technical Reports Server (NTRS)

    Shaw, Harry C. (Inventor); Ott, Melanie N. (Inventor); Manuel, Michele V. (Inventor)

    2002-01-01

    A process of fabricating a fiber device includes providing a hollow core fiber, and forming a sol-gel material inside the hollow core fiber. The hollow core fiber is preferably an optical fiber, and the sol-gel material is doped with a dopant. Devices made in this manner includes a wide variety of sensors.

  4. Orf5/SolR: a transcriptional repressor of the sol operon of Clostridium acetobutylicum?

    PubMed

    Thormann, K; Dürre, P

    2001-11-01

    The gene of Orf5 (SolR) of Clostridium acetobutylicum DSM 792 was subcloned and overexpressed in Escherichia coli. The protein was purified with Ni-NTA agarose and used for DNA binding assays. No DNA binding of Orf5 to regions upstream of the sol operon from C. acetobutylicum was observed. Overexpression of Orf5 in C. acetobutylicum led to a change in the organism's pattern of glycosylated exoproteins. The Orf5 protein was localized in the cell membrane fraction and to a small extent in the supernatant medium. Based on these results Orf5 (SolR) appears not to act as a transcriptional repressor in C. acetobutylicum, but instead may be an enzyme involved in glycosylation or deglycosylation.

  5. 'Papillary' solitary fibrous tumor/hemangiopericytoma with nuclear STAT6 expression and NAB2-STAT6 fusion.

    PubMed

    Ishizawa, Keisuke; Tsukamoto, Yoshitane; Ikeda, Shunsuke; Suzuki, Tomonari; Homma, Taku; Mishima, Kazuhiko; Nishikawa, Ryo; Sasaki, Atsushi

    2016-04-01

    This report describes clinicopathological findings, including genetic data of STAT6, in a solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) of the central nervous system in an 83-year-old woman with a bulge in the left forehead. She noticed it about 5 months before, and it had grown rapidly for the past 1 month. Neuroradiological studies disclosed a well-demarcated tumor that accompanied the destruction of the skull. The excised tumor showed a prominent papillary structure, where atypical cells were compactly arranged along the fibrovascular core ('pseudopapillary'). There was rich vasculature, some of which resembled 'staghorn' vessels. Mitotic figures were occasionally found. Whorls, psammoma bodies, or intra-nuclear pseudoinclusions were not identified. By immunohistochemistry, CD34 was strongly positive in the tumor cells, and STAT6 was localized in their nuclei. By reverse transcription-polymerase chain reaction (RT-PCR), an NAB2-STAT6 fusion gene, NAB2 exon6-STAT6 exon17, was detected, establishing a definite diagnosis of SFT/HPC. 'Papillary' SFT/HPC needs to be recognized as a possible morphological variant of SFT/HPC, and should be borne in mind in its diagnostic practice.

  6. Stat3 orchestrates interaction between endothelial and tumor cells and inhibition of Stat3 suppresses brain metastasis of breast cancer cells.

    PubMed

    Lee, Hsueh-Te; Xue, Jianfei; Chou, Ping-Chieh; Zhou, Aidong; Yang, Phillip; Conrad, Charles A; Aldape, Kenneth D; Priebe, Waldemar; Patterson, Cam; Sawaya, Raymond; Xie, Keping; Huang, Suyun

    2015-04-30

    Brain metastasis is a major cause of morbidity and mortality in patients with breast cancer. Our previous studies indicated that Stat3 plays an important role in brain metastasis. Here, we present evidence that Stat3 functions at the level of the microenvironment of brain metastases. Stat3 controlled constitutive and inducible VEGFR2 expression in tumor-associated brain endothelial cells. Furthermore, inhibition of Stat3 by WP1066 decreased the incidence of brain metastases and increased survival in a preclinical model of breast cancer brain metastasis. WP1066 inhibited Stat3 activation in tumor-associated endothelial cells, reducing their infiltration and angiogenesis. WP1066 also inhibited breast cancer cell invasion. Our results indicate that WP1066 can inhibit tumor angiogenesis and brain metastasis mediated by Stat3 in endothelial and tumor cells.

  7. STAT-dependent upregulation of 12/15-lipoxygenase contributes to neuronal injury after stroke

    PubMed Central

    Jung, Joo Eun; Karatas, Hulya; Liu, Yu; Yalcin, Ayfer; Montaner, Joan; Lo, Eng H; van Leyen, Klaus

    2015-01-01

    Oxidative stress is a major brain injury mechanism after ischemic stroke. 12/15-lipoxygenase (12/15-LOX) is a key mediator of oxidative stress, contributing to neuronal cell death and vascular leakage. Nonetheless, the mechanism leading to its upregulation is currently unknown. We show here that Signal Transducers and Activators of Transcription (STATs), specifically STAT6 and possibly STAT1, increase transcription of 12/15-LOX in neuronal cells. Both p-STAT6 and -1 bound to specific STAT binding sites in the mouse 12/15-LOX promoter. Small interfering RNA (siRNA) knockdown showed STAT6 to be the dominant regulator, reducing 12/15-LOX promoter activation and cell death in oxidatively stressed HT22 cells. STAT6 siRNA efficiently prevented the increase of 12/15-LOX in murine primary neurons, both after induction of oxidative stress and after oxygen-glucose deprivation. Early activation of STAT6 and STAT1 in mice was consistent with a role in regulating 12/15-LOX in focal ischemia. Brains of human stroke patients showed increased p-STAT6 and p-STAT1 in the peri-infarct region, along with 12/15-LOX and markers of apoptosis. These results link STAT6 and STAT1 to the 12/15-LOX damage pathway and suggest disregulation of STAT-dependent transcription as injury mechanism in stroke. Selectively targeting STATs may thus be a novel therapeutic approach to reducing brain injury after a stroke. PMID:26174325

  8. Method of making particles from an aqueous sol

    DOEpatents

    Rankin, G.W.; Hooker, J.R.

    1973-07-24

    A process for preparing gel particles from an aqueous sol by forming the sol into droplets in a liquid system wherein the liquid phase contains a liquid organic solvent and a barrier agent. The barrier agent prevents dehydration from occurring too rapidly and permits surface tension effects to form sol droplets into the desired spheroidal shape. A preferred barrier agent is mineral oil. (Official Gazette)

  9. STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by sirtuin 1 through a direct inhibition of STAT3 acetylation.

    PubMed

    Sestito, Rosanna; Madonna, Stefania; Scarponi, Claudia; Cianfarani, Francesca; Failla, Cristina M; Cavani, Andrea; Girolomoni, Giampiero; Albanesi, Cristina

    2011-03-01

    IL-22 has a pathogenetic role in psoriasis, where it is responsible for the altered proliferation and differentiation of keratinocytes and induces inflammatory molecules. The IL-22-induced effects are mediated by STAT3, whose activity is proportional to acetylation in lysine (Lys)685 and phosphorylation in tyrosine (Tyr)705. Lys 685 acetylation of STAT3 is inhibited by sirtuin (SIRT)1, a class III deacetylase promoting keratinocyte differentiation. Due to the opposite effects of IL-22 and SIRT1, we investigated whether IL-22-induced effects in keratinocytes could be regulated by SIRT1 through control of STAT3. We found that SIRT1 opposes the IL-22-induced STAT3 activity by deacetylating STAT3 and reducing STAT3 Tyr705 phosphorylation. By controlling STAT3, SIRT1 also influences the IL-22-induced expression of molecules involved in proliferation and inflammation as well as proliferation and migration processes in cultured keratinocytes. Although SIRT1 levels were similar in keratinocytes of healthy individuals and patients with psoriasis, they were reduced in psoriatic skin lesions, with the lymphokine IFN-γ inhibiting SIRT1 expression. Concomitantly, IFN-γ enhanced basal acetylation of STAT3 and its phosphorylation induced by IL-22. In conclusion, STAT3-dependent IL-22 signaling and effects in keratinocytes are negatively regulated by SIRT1. In skin affected by psoriasis, SIRT1 is down-regulated by IFN-γ, which thus renders psoriatic keratinocytes more prone to respond to IL-22.

  10. StreamStats in Georgia: a water-resources web application

    USGS Publications Warehouse

    Gotvald, Anthony J.; Musser, Jonathan W.

    2015-07-31

    StreamStats is being implemented on a State-by-State basis to allow for customization of the data development and underlying datasets to address their specific needs, issues, and objectives. The USGS, in cooperation with the Georgia Environmental Protection Division and Georgia Department of Transportation, has implemented StreamStats for Georgia. The Georgia StreamStats Web site is available through the national StreamStats Web-page portal at http://streamstats.usgs.gov. Links are provided on this Web page for individual State applications, instructions for using StreamStats, definitions of basin characteristics and streamflow statistics, and other supporting information.

  11. STAT3 as a target for inducing apoptosis in solid and hematological tumors

    PubMed Central

    Siddiquee, Khandaker Al Zaid; Turkson, James

    2008-01-01

    Studies in the past few years have provided compelling evidence for the critical role of aberrant Signal Transducer and Activator of Transcription 3 (STAT3) in malignant transformation and tumorigenesis. Thus, it is now generally accepted that STAT3 is one of the critical players in human cancer formation and represents a valid target for novel anticancer drug design. This review focuses on aberrant STAT3 and its role in promoting tumor cell survival and supporting the malignant phenotype. A brief evaluation of the current strategies targeting STAT3 for the development of novel anticancer agents against human tumors harboring constitutively active STAT3 will also be presented. PMID:18227858

  12. Comment on “Maxwell's equations and electromagnetic Lagrangian density in fractional form” [J. Math. Phys. 53, 033505 (2012)

    SciTech Connect

    Rabei, Eqab M.; Al-Jamel, A.; Widyan, H.; Baleanu, D.

    2014-03-15

    In a recent paper, Jaradat et al. [J. Math. Phys. 53, 033505 (2012)] have presented the fractional form of the electromagnetic Lagrangian density within the Riemann-Liouville fractional derivative. They claimed that the Agrawal procedure [O. P. Agrawal, J. Math. Anal. Appl. 272, 368 (2002)] is used to obtain Maxwell's equations in the fractional form, and the Hamilton's equations of motion together with the conserved quantities obtained from fractional Noether's theorem are reported. In this comment, we draw the attention that there are some serious steps of the procedure used in their work are not applicable even though their final results are correct. Their work should have been done based on a formulation as reported by Baleanu and Muslih [Phys. Scr. 72, 119 (2005)].

  13. Comment on "Maxwell's equations and electromagnetic Lagrangian density in fractional form" [J. Math. Phys. 53, 033505 (2012)

    NASA Astrophysics Data System (ADS)

    Rabei, Eqab M.; Al-Jamel, A.; Widyan, H.; Baleanu, D.

    2014-03-01

    In a recent paper, Jaradat et al. [J. Math. Phys. 53, 033505 (2012)] have presented the fractional form of the electromagnetic Lagrangian density within the Riemann-Liouville fractional derivative. They claimed that the Agrawal procedure [O. P. Agrawal, J. Math. Anal. Appl. 272, 368 (2002)] is used to obtain Maxwell's equations in the fractional form, and the Hamilton's equations of motion together with the conserved quantities obtained from fractional Noether's theorem are reported. In this comment, we draw the attention that there are some serious steps of the procedure used in their work are not applicable even though their final results are correct. Their work should have been done based on a formulation as reported by Baleanu and Muslih [Phys. Scr. 72, 119 (2005)].

  14. Sol-gel processing with inorganic metal salt precursors

    DOEpatents

    Hu, Zhong-Cheng

    2004-10-19

    Methods for sol-gel processing that generally involve mixing together an inorganic metal salt, water, and a water miscible alcohol or other organic solvent, at room temperature with a macromolecular dispersant material, such as hydroxypropyl cellulose (HPC) added. The resulting homogenous solution is incubated at a desired temperature and time to result in a desired product. The methods enable production of high quality sols and gels at lower temperatures than standard methods. The methods enable production of nanosize sols from inorganic metal salts. The methods offer sol-gel processing from inorganic metal salts.

  15. Gradient Index Lenses From Sol-Gel Layering.

    DTIC Science & Technology

    2008-02-15

    AND SJu ’ jL SGFRADIENT INDEX LENSES FROM SOL - GEL LAYERING F49620-93-1-0364 3484/XS 6. AU1CqQ(s) ) 61103D Dr John D. Mackenzie 4 7. PE’r~Of;M1!?𔃽...applied U to the sol -ge•l process. The sol - gel process has been widely studied in the Uj recent past, as it is an interesting alte’rnative chemical route...REPORT to Air Force Office of Scientific Research for project entitled GRADIENT INDEX LENSES FROM SOL - GEL LAYERING (An AASERT Award) Grant No.: AFOSR

  16. Method of making ionic liquid mediated sol-gel sorbents

    DOEpatents

    Malik, Abdul; Shearrow, Anne M.

    2017-01-31

    Ionic liquid (IL)-mediated sol-gel hybrid organic-inorganic materials present enormous potential for effective use in analytical microextraction. One obstacle to materializing this prospect arises from high viscosity of ILs significantly slowing down sol-gel reactions. A method was developed which provides phosphonium-based, pyridinium-based, and imidazolium-based IL-mediated advanced sol-gel organic-inorganic hybrid materials for capillary microextraction. Scanning electron microscopy results demonstrate that ILs can serve as porogenic agents in sol-gel reactions. IL-mediated sol-gel coatings prepared with silanol-terminated polymers provided up to 28 times higher extractions compared to analogous sol-gel coatings prepared without any IL in the sol solution. This study shows that IL-generated porous morphology alone is not enough to provide effective extraction media: careful choice of the organic polymer and the precursor with close sol-gel reactivity must be made to ensure effective chemical bonding of the organic polymer to the created sol-gel material to be able to provide the desired sorbent characteristics.

  17. Comment on "Analysis of single-layer metamaterial absorber with reflection theory" [J. Appl. Phys. 117, 154906 (2015)

    NASA Astrophysics Data System (ADS)

    Tung, Nguyen Thanh

    2016-03-01

    In a recent paper, Xiong et al. [J. Appl. Phys. 117, 154906 (2015)] presented the simulated results of a Jerusalem-cross structure in an attempt to elaborate their proposed reflection theory for metamaterial absorbers. Noting that even at non-resonant frequencies the real part of the permeability shows an over-high average value and its imaginary part drops abruptly from positivity to negativity, we argue that their simulated results are unphysical, resulting from an incomplete understanding of the retrieval procedure.

  18. Comment on 'Power loss in open cavity diodes and a modified Child-Langmuir law' [Phys. Plasmas 12, 093102 (2005)

    SciTech Connect

    Swanekamp, S. B.; Ottinger, P. F.

    2007-09-15

    In this Comment, it is shown that no modification of the Child-Langmuir law [Phys. Rev.32, 492 (1911); Phys. Rev. 2, 450 (1913)] is necessary to treat the space-charge-limited flow from a diode with an open boundary as reported in Phys. Plasmas 12, 093102 (2005). The open boundary condition in their simulations can be represented by a voltage source and a resistor whose value is the vacuum-wave impedance of the opening. The diode can be represented as a variable resistor whose value depends on the voltage drop across the diode (as measured by the line integral of E across the diode gap). This is a simple voltage-divider circuit whose analysis shows that the real diode voltage drops as the vacuum-wave impedance increases. Furthermore, it is shown that in equilibrium, the voltage drop between the anode and cathode is independent of the path chosen for the line integral of the electric field so that E=-{nabla}{phi} is valid. In this case, the equations of electrostatics are applicable. This clearly demonstrates that the electric field is electrostatic and static fields DO NOT RADIATE. It is shown that the diode voltage drops as the vacuum wave impedance increases and the current drops according to the Child-Langmuir law. Therefore, the observed drop in circuit current can be explained by a real drop in voltage across the diode and not an effective drop as claimed by the authors.

  19. Comment on ``Unified explanation of the anomalous dynamic properties of highly asymmetric polymer blends'' [J. Chem. Phys. 138, 054903 (2013)

    NASA Astrophysics Data System (ADS)

    Colmenero, J.

    2013-05-01

    In a recent paper by Ngai and Capaccioli ["Unified explanation of the anomalous dynamic properties of highly asymmetric polymer blends," J. Chem. Phys. 138, 054903 (2013), 10.1063/1.4789585] the authors claimed that the so-called coupling model (CM) provides a unified explanation of all dynamical anomalies that have been reported for dynamically asymmetric blends over last ten years. Approximately half of the paper is devoted to chain-dynamic properties involving un-entangled polymers. According to the authors, the application of the CM to these results is based on the existence of a crossover at a time tc ≈ 1-2 ns of the magnitudes describing chain-dynamics. Ngai and Capaccioli claimed that the existence of such a crossover is supported by the neutron scattering and MD-simulation results, corresponding to the blend poly(methyl methacrylate)/poly(ethylene oxide), by Niedzwiedz et al. [Phys. Rev. Lett. 98, 168301 (2007), 10.1103/PhysRevLett.98.168301] and Brodeck et al. [Macromolecules 43, 3036 (2010), 10.1021/ma902820a], respectively. Being one of the authors of these two papers, I will demonstrate here that there is no evidence supporting such a crossover in the data reported in these papers.

  20. Nifuroxazide inhibits survival of multiple myeloma cells by directly inhibiting STAT3.

    PubMed

    Nelson, Erik A; Walker, Sarah R; Kepich, Alicia; Gashin, Laurie B; Hideshima, Teru; Ikeda, Hiroshi; Chauhan, Dharminder; Anderson, Kenneth C; Frank, David A

    2008-12-15

    Constitutive activation of the transcription factor STAT3 contributes to the pathogenesis of many cancers, including multiple myeloma (MM). Since STAT3 is dispensable in most normal tissue, targeted inhibition of STAT3 is an attractive therapy for patients with these cancers. To identify STAT3 inhibitors, we developed a transcriptionally based assay and screened a library of compounds known to be safe in humans. We found the drug nifuroxazide to be an effective inhibitor of STAT3 function. Nifuroxazide inhibits the constitutive phosphorylation of STAT3 in MM cells by reducing Jak kinase autophosphorylation, and leads to down-regulation of the STAT3 target gene Mcl-1. Nifuroxazide causes a decrease in viability of primary myeloma cells and myeloma cell lines containing STAT3 activation, but not normal peripheral blood mononuclear cells. Although bone marrow stromal cells provide survival signals to myeloma cells, nifuroxazide can overcome this survival advantage. Reflecting the interaction of STAT3 with other cellular pathways, nifuroxazide shows enhanced cytotoxicity when combined with either the histone deacetylase inhibitor depsipeptide or the MEK inhibitor UO126. Therefore, using a mechanistic-based screen, we identified the clinically relevant drug nifuroxazide as a potent inhibitor of STAT signaling that shows cytotoxicity against myeloma cells that depend on STAT3 for survival.

  1. STAT6 deficiency ameliorates Graves' disease severity by suppressing thyroid epithelial cell hyperplasia

    PubMed Central

    Jiang, Xuechao; Zha, Bingbing; Liu, Xiaoming; Liu, Ronghua; Liu, Jun; Huang, Enyu; Qian, Tingting; Liu, Jiajing; Wang, Zhiming; Zhang, Dan; Wang, Luman; Chu, Yiwei

    2016-01-01

    Signal transducer and activator of transcription 6 (STAT6) is involved in epithelial cell growth. However, little is known regarding the STAT6 phosphorylation status in Graves' disease (GD) and its role in thyroid epithelial cells (TECs). In this study, we found that STAT6 phosphorylation (p-STAT6) was significantly increased in TECs from both GD patients and experimental autoimmune Graves' disease mice and that STAT6 deficiency ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the phosphorylation of STAT6 via IL-4 R engagement, and the downstream targets of STAT6 were Bcl-xL and cyclin D1. Thus, the IL-4-STAT6-Bcl-xL/cyclin D1 pathway is crucial for TEC hyperplasia, which aggravates GD. More importantly, in vitro and in vivo experiments demonstrated that STAT6 phosphorylation inhibited by AS1517499 decreased TEC hyperplasia, thereby reducing serum T3 and T4 and ameliorating GD. Thus, our study reveals that in addition to the traditional pathogenesis of GD, in which autoantibody TRAb stimulates thyroid-stimulating hormone receptors and consequently produces T3, T4, TRAb could also trigger TECs producing IL-4, and IL-4 then acts in an autocrine manner to activate p-STAT6 signalling and stimulate unrestricted cell growth, thus aggravating GD. These findings suggest that STAT6 inhibitors could be potent therapeutics for treating GD. PMID:27906181

  2. STAT1 Pathway Mediates Amplification of Metastatic Potential and Resistance to Therapy

    PubMed Central

    Pitroda, Sean P.; Golden, Daniel W.; Bhayani, Mihir; Shao, Michael Y.; Darga, Thomas E.; Beveridge, Mara G.; Sood, Ravi F.; Sutton, Harold G.; Beckett, Michael A.; Mauceri, Helena J.; Posner, Mitchell C.; Weichselbaum, Ralph R.

    2009-01-01

    Background Traditionally IFN/STAT1 signaling is connected with an anti-viral response and pro-apoptotic tumor-suppressor functions. Emerging functions of a constitutively activated IFN/STAT1 pathway suggest an association with an aggressive tumor phenotype. We hypothesized that tumor clones that constitutively overexpress this pathway are preferentially selected by the host microenvironment due to a resistance to STAT1-dependent cytotoxicity and demonstrate increased metastatic ability combined with increased resistance to genotoxic stress. Methodology/Principal Findings Here we report that clones of B16F1 tumors grown in the lungs of syngeneic C57BL/6 mice demonstrate variable transcriptional levels of IFN/STAT1 pathway expression. Tumor cells that constitutively overexpress the IFN/STAT1 pathway (STAT1H genotype) are selected by the lung microenvironment. STAT1H tumor cells also demonstrate resistance to IFN-gamma (IFNγ), ionizing radiation (IR), and doxorubicin relative to parental B16F1 and low expressors of the IFN/STAT1 pathway (STAT1L genotype). Stable knockdown of STAT1 reversed the aggressive phenotype and decreased both lung colonization and resistance to genotoxic stress. Conclusions Our results identify a pathway activated by tumor-stromal interactions thereby selecting for pro-metastatic and therapy-resistant tumor clones. New therapies targeted against the IFN/STAT1 signaling pathway may provide an effective strategy to treat or sensitize aggressive tumor clones to conventional cancer therapies and potentially prevent distant organ colonization. PMID:19503789

  3. Molecular cloning and expression analysis of the STAT1 gene in the water buffalo (Bubalus bubalis).

    PubMed

    Deng, Tingxian; Pang, Chunying; Zhu, Peng; Liao, Biyun; Zhang, Ming; Yang, Bingzhuang; Liang, Xianwei

    2015-01-01

    Signal transducer and activator of transcription 1 (STAT1) is a critical component of the transcription factor complex in the interferon (IFN) signaling pathways. Of the seven STAT isoforms, STAT1 is a key mediator of type I and type III IFN signaling, but limited information is available for the STAT genes in the water buffalo. Here, we amplified and identified the complete coding sequence (CDS) of the buffalo STAT1 gene by using reverse transcription polymerase chain reaction (RT-PCR). Sequence analysis indicated that the buffalo STAT1 gene length size was 3437 bp, containing an open reading frame (ORF) of 2244 bp that encoded 747 amino acids for the first time. The buffalo STAT1 CDS showed 99, 98, 89, 93, 86, 85, and 87% identity with that of Bos taurus, Ovis aries, Homo sapiens, Sus scrofa, Rattus norvegicus, Mus musculus, and Capra hircus. The phylogenetic analyses revealed that the nearest relationship existed between the water buffalo and B. taurus. The STAT1 gene was ubiquitously expressed in 11 buffalo tissues by real-time PCR, whereas STAT1 was expressed at higher levels in the lymph. The STAT1 gene contained five targeted microRNA sequences compared with the B. taurus by the miRBase software that provide a fundamental for identifying the STAT1 gene function.

  4. Interplay of hepatic and myeloid STAT3 in facilitating liver regeneration via tempering innate immunity

    PubMed Central

    Wang, Hua; Park, Ogyi; Lafdil, Fouad; Shen, Kezhen; Horiguchi, Norio; Yin, Shi; Fu, Xin-Yuan; Kunos, George; Gao, Bin

    2009-01-01

    Liver regeneration triggered by 2/3 partial hepatectomy is accompanied by elevated hepatic levels of endotoxin, which contributes to the regenerative process, but liver inflammation and apoptosis remain paradoxically limited. Here we show that STAT3, an important anti-inflammatory signal, is activated in myeloid cells after partial hepatectomy and its conditional deletion results in an enhanced inflammatory response. Surprisingly, this is accompanied by an improved rather than impaired regenerative response with increased hepatic STAT3 activation, which may contribute to the enhanced liver regeneration. Indeed, conditional deletion of STAT3 in both hepatocytes and myeloid cells results in elevated activation of STAT1 and apoptosis of hepatocytes, and a dramatic reduction in survival after partial hepatectomy, whereas additional global deletion of STAT1 protects against these effects. Conclusions: An interplay of myeloid and hepatic STAT3 signaling is essential to prevent liver failure during liver regeneration through tempering a strong innate inflammatory response mediated by STAT1 signaling. PMID:20041412

  5. Stat3 is involved in control of MASP2 gene expression

    SciTech Connect

    Unterberger, Claudia; Hanson, Steven; Klingenhoff, Andreas; Oesterle, Daniela; Frankenberger, Marion; Endo, Yuichi; Matsushita, Misao; Fujita, Teizo; Schwaeble, Wilhelm; Weiss, Elisabeth H.; Ziegler-Heitbrock, Loems; Stover, Cordula

    2007-12-28

    Little is known about determinants regulating expression of Mannan-binding lectin associated serine protease-2 (MASP-2), the effector component of the lectin pathway of complement activation. Comparative bioinformatic analysis of the MASP2 promoter regions in human, mouse, and rat, revealed conservation of two putative Stat binding sites, termed StatA and StatB. Site directed mutagenesis specific for these sites was performed. Transcription activity was decreased 5-fold when StatB site was mutated in the wildtype reporter gene construct. Gel retardation and competition assays demonstrated that proteins contained in the nuclear extract prepared from HepG2 specifically bound double-stranded StatB oligonucleotides. Supershift analysis revealed Stat3 to be the major specific binding protein. We conclude that Stat3 binding is important for MASP2 promoter activity.

  6. Growth hormone, but not insulin, activates STAT5 proteins in adipocytes in vitro and in vivo.

    PubMed

    Zvonic, Sanjin; Story, David J; Stephens, Jacqueline M; Mynatt, Randall L

    2003-03-07

    STAT 5 proteins are latent transcription factors which have been shown to be activated by growth hormone (GH) in many cell types. However, some recent studies also suggest that STAT 5B is a physiological substrate of the insulin receptor. In our studies, we have shown that physiological levels of insulin do not induce STAT 5 tyrosine phosphorylation or affect the nuclear distribution of STATs 5A or 5B in 3T3-L1 adipocytes. Moreover, we did not observe the activation of STAT 5 in the adipose tissue or skeletal muscle of mice following an acute intraperitoneal injection of insulin. However, acute GH administration, both in vitro and in vivo, resulted in the activation of STAT 5 proteins. In summary, our results indicate that STAT 5 proteins are not activated by physiological levels of insulin in adipose tissue.

  7. Impaired IL-13-mediated functions of macrophages in STAT6-deficient mice.

    PubMed

    Takeda, K; Kamanaka, M; Tanaka, T; Kishimoto, T; Akira, S

    1996-10-15

    IL-13 shares many biologic responses with IL-4. In contrast to well-characterized IL-4 signaling pathways, which utilize STAT6 and 4PS/IRS2, IL-13 signaling pathways are poorly understood. Recent studies performed with STAT6-deficient mice have demonstrated that STAT6 plays an essential role in IL-4 signaling. In this study, the functions of peritoneal macrophages of STAT6-deficient mice in response to IL-13 were analyzed. In STAT6-deficient mice, neither morphologic changes nor augmentation of MHC class II expression in response to IL-13 was observed. In addition, IL-13 did not decrease the nitric oxide production by activated macrophages. Taken together, these results suggest that the macrophage functions in response to IL-13 were impaired in STAT6-deficient mice, indicating that IL-13 and IL-4 share the signaling pathway via STAT6.

  8. KAP1 regulates type I interferon/STAT1-mediated IRF-1 gene expression

    SciTech Connect

    Kamitani, Shinya; Ohbayashi, Norihiko; Ikeda, Osamu; Togi, Sumihito; Muromoto, Ryuta; Sekine, Yuichi; Ohta, Kazuhide; Ishiyama, Hironobu; Matsuda, Tadashi

    2008-05-30

    Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation, and survival in immune responses, hematopoiesis, neurogenesis, and other biological processes. Recently, we showed that KAP1 is a novel STAT-binding partner that regulates STAT3-mediated transactivation. KAP1 is a universal co-repressor protein for the KRAB zinc finger protein superfamily of transcriptional repressors. In this study, we found KAP1-dependent repression of interferon (IFN)/STAT1-mediated signaling. We also demonstrated that endogenous KAP1 associates with endogenous STAT1 in vivo. Importantly, a small-interfering RNA-mediated reduction in KAP1 expression enhanced IFN-induced STAT1-dependent IRF-1 gene expression. These results indicate that KAP1 may act as an endogenous regulator of the IFN/STAT1 signaling pathway.

  9. Cross-talk between KLF4 and STAT3 regulates axon regeneration

    NASA Astrophysics Data System (ADS)

    Qin, Song; Zou, Yuhua; Zhang, Chun-Li

    2013-10-01

    Cytokine-induced activation of signal transducer and activator of transcription 3 (STAT3) promotes the regrowth of damaged axons in the adult central nervous system (CNS). Here we show that KLF4 physically interacts with STAT3 upon cytokine-induced phosphorylation of tyrosine 705 (Y705) on STAT3. This interaction suppresses STAT3-dependent gene expression by blocking its DNA-binding activity. The deletion of KLF4 in vivo induces axon regeneration of adult retinal ganglion cells (RGCs) via Janus kinase (JAK)-STAT3 signalling. This regeneration can be greatly enhanced by exogenous cytokine treatment, or removal of an endogenous JAK-STAT3 pathway inhibitor called suppressor of cytokine signalling 3 (SOCS3). These findings reveal an unexpected cross-talk between KLF4 and activated STAT3 in the regulation of axon regeneration that might have therapeutic implications in promoting repair of injured adult CNS.

  10. Comment on “Theoretical analysis of high-field transport in graphene on a substrate” [J. Appl. Phys. 116, 034507 (2014)

    SciTech Connect

    Tan, Michael L. P.; Arora, Vijay K.

    2014-12-21

    In a recent article, Serov et al. [J. Appl. Phys. 116, 034507 (2014)] claim: “This study represents the first time that the high-field behavior in graphene on a substrate was investigated taking into account intrinsic graphene properties,” ignoring the most recent anisotropic distribution function [V. K. Arora et al., J. Appl. Phys. 112, 114330 (2012)] also published in J. Appl. Phys., targeting the same experimental data [V. E. Dorgan et al., Appl. Phys. Lett. 97, 082112 (2010)]. The claim of Serov et al. of being first is refuted and many shortcomings of the hydrodynamic model for a highly quantum and degenerate graphene nanolayer are pointed out.

  11. 'Victoria' After Sol 950 Drive (Stereo)

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Left-eye view of a stereo pair for PIA08778

    [figure removed for brevity, see original site] Right-eye view of a stereo pair for PIA08778 [figure removed for brevity, see original site] Cylindrical view for PIA08778

    A drive of about 30 meters (about 100 feet) on the 950th Martian day, or sol, of Opportunity's exploration of Mars' Meridiani Planum region (Sept. 25, 2006) brought the NASA rover to within about 20 meters (about 66 feet) of the rim of 'Victoria Crater.' From that position, the rover's navigation camera took the exposures combined into this stereo anaglyph, which appears three-dimensional when viewed through red-green glasses. The scalloped shape of the crater is visible on the left edge. Due to a small dune or ripple close to the nearest part of the rim, the scientists and engineers on the rover team planned on sol 951 to drive to the right of the ripple, but not quite all the way to the rim, then to proceed to the rim the following sol. The image is presented in cylindrical projection with geometric seam correction.

    Victoria Crater is about 800 meters (one-half mile) in diameter, about five times wider than 'Endurance Crater,' which Opportunity spent six months examining in 2004, and about 40 times wider than 'Eagle Crater,' where Opportunity first landed. The great lure of Victoria is the expectation that a thick stack of geological layers will be exposed in the crater walls, potentially several times the thickness that was previously studied at Endurance and therefore, potentially preserving several times the historical record.

  12. Spirit's Surroundings on 'West Spur,' Sol 305

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This 360-degree panorama shows the terrain surrounding NASA's Mars Exploration Rover Spirit as of the rover's 305th martian day, or sol, (Nov. 11, 2004). At that point, Spirit was climbing the 'West Spur' of the 'Columbia Hills.' The rover had just finished inspecting a rock called 'Lutefisk' and was heading uphill toward an area called 'Machu Picchu.' Spirit used its navigational camera to take the images combined into this mosaic. The rover's location when the images were taken is catalogued as the mission's site 89, position 205. The view is presented here as a cylindrical projection with geometric seam correction.

  13. The Sol-Gel-Xerogel Transition

    DTIC Science & Technology

    1993-11-01

    cases, on the matrix of the gel. They showed that photofading of methylene blue in thin films prepared from methyltriethoxy-silane is faster than In films...thin films doped with zeolite crystals (>1 pim, ZSM-5) benefit from the size exclusion selectivity of the encased zeolites . 2. Control of the surface...exposed to H2S due to the formation of CdS crystals. Zink and 0 Dunn [33] reported that sol-gel glasses doped with iron(III) produce an intense blue

  14. Exterior of Opportunity Heat Shield, Sol 344

    NASA Technical Reports Server (NTRS)

    2005-01-01

    NASA's Mars Exploration Rover Opportunity took a detailed look at what was once the exterior of its heat shield. Hitting the martian surface inverted the heat shield, making it difficult to photograph the outside where evidence of any atmospheric effects may be found.

    Engineers sought this image to help determine how the heat shield weathered the intense frictional heat created as it passed through the martian atmosphere.

    This is an approximately true-color rendering of the scene acquired around 12:47 p.m. local solar time on Opportunity's sol 344 (Jan. 11, 2005) using panoramic camera filters at wavelengths of 750, 530, and 430 nanometers.

  15. Spirit Near 'Stapledon' on Sol 1802 (Stereo)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    [figure removed for brevity, see original site] Left-eye view of a color stereo pair for PIA11781 [figure removed for brevity, see original site] Right-eye view of a color stereo pair for PIA11781

    NASA Mars Exploration Rover Spirit used its navigation camera for the images assembled into this stereo, full-circle view of the rover's surroundings during the 1,802nd Martian day, or sol, (January 26, 2009) of Spirit's mission on the surface of Mars. South is at the center; north is at both ends.

    This view combines images from the left-eye and right-eye sides of the navigation camera. It appears three-dimensional when viewed through red-blue glasses with the red lens on the left.

    Spirit had driven down off the low plateau called 'Home Plate' on Sol 1782 (January 6, 2009) after spending 12 months on a north-facing slope on the northern edge of Home Plate. The position on the slope (at about the 9-o'clock position in this view) tilted Spirit's solar panels toward the sun, enabling the rover to generate enough electricity to survive its third Martian winter. Tracks at about the 11-o'clock position of this panorama can be seen leading back to that 'Winter Haven 3' site from the Sol 1802 position about 10 meters (33 feet) away. For scale, the distance between the parallel wheel tracks is about one meter (40 inches).

    Where the receding tracks bend to the left, a circular pattern resulted from Spirit turning in place at a soil target informally named 'Stapledon' after William Olaf Stapledon, a British philosopher and science-fiction author who lived from 1886 to 1950. Scientists on the rover team suspected that the soil in that area might have a high concentration of silica, resembling a high-silica soil patch discovered east of Home Plate in 2007. Bright material visible in the track furthest to the right was examined with Spirit's alpha partical X-ray spectrometer and found, indeed, to be rich in silica.

    The team laid plans to drive Spirit from

  16. STAT1 negatively regulates spatial memory formation and mediates the memory-impairing effect of Aβ.

    PubMed

    Hsu, Wei-Lun; Ma, Yun-Li; Hsieh, Ding-You; Liu, Yen-Chen; Lee, Eminy Hy

    2014-02-01

    Signal transducer and activator of transcription-1 (STAT1) has an important role in inflammation and the innate immune response, but its role in the central nervous system is less well understood. Here, we examined the role of STAT1 in spatial learning and memory, and assessed the involvement of STAT1 in mediating the memory-impairing effect of amyloid-beta (Aβ). We found that water maze training downregulated STAT1 expression in the rat hippocampal CA1 area, and spatial learning and memory function was enhanced in Stat1-knockout mice. Conversely, overexpression of STAT1 impaired water maze performance. STAT1 strongly upregulated the expression of the extracellular matrix protein laminin β1 (LB1), which also impaired water maze performance in rats. Furthermore, Aβ impaired spatial learning and memory in association with a dose-dependent increase in STAT1 and LB1 expression, but knockdown of STAT1 and LB1 both reversed this effect of Aβ. This Aβ-induced increase in STAT1 and LB1 expression was also associated with a decrease in the expression of the N-methyl-D-aspartate receptor (NMDAR) subunits, NR1, and NR2B. Overexpression of NR1 or NR2B or exogenous application of NMDA reversed Aβ-induced learning and memory deficits as well as Aβ-induced STAT1 and LB1 expression. Our results demonstrate that STAT1 negatively regulates spatial learning and memory through transcriptional regulation of LB1 expression. We also identified a novel mechanism for Aβ pathogenesis through STAT1 induction. Notably, impairment of spatial learning and memory by this STAT1-mediated mechanism is independent of cAMP responsive element-binding protein signaling.

  17. Suppression of autophagy augments the radiosensitizing effects of STAT3 inhibition on human glioma cells

    SciTech Connect

    Yuan, Xiaopeng; Du, Jie; Hua, Song; Zhang, Haowen; Gu, Cheng; Wang, Jie; Yang, Lei; Huang, Jianfeng; Yu, Jiahua Liu, Fenju

    2015-01-15

    Radiotherapy is an essential component of the standard therapy for newly diagnosed glioblastoma. To increase the radiosensitivity of glioma cells is a feasible solution to improve the therapeutic effects. It has been suggested that inhibition of signal transducer and activator of transcription 3 (STAT3) can radiosensitize glioma cells, probably via the activation of mitochondrial apoptotic pathway. In this study, human malignant glioma cells, U251 and A172, were treated with an STAT3 inhibitor, WP1066, or a short hairpin RNA plasmid targeting STAT3 to suppress the activation of STAT3 signaling. The radiosensitizing effects of STAT3 inhibition were confirmed in glioma cells. Intriguingly, combination of ionizing radiation exposure and STAT3 inhibition triggered a pronounced increase of autophagy flux. To explore the role of autophagy, glioma cells were treated with 3-methyladenine or siRNA for autophagy-related gene 5, and it was demonstrated that inhibition of autophagy further strengthened the radiosensitizing effects of STAT3 inhibition. Accordingly, more apoptotic cells were induced by the dual inhibition of autophagy and STAT3 signaling. In conclusion, our data revealed a protective role of autophagy in the radiosensitizing effects of STAT3 inhibition, and inhibition of both autophagy and STAT3 might be a potential therapeutic strategy to increase the radiosensitivity of glioma cells. - Highlights: • Inactivation of STAT3 signaling radiosensitizes malignant glioma cells. • STAT3 inhibition triggers a significant increase of autophagy flux induced by ionizing radiation in glioma cells. • Suppression of autophagy further strengthens the radiosensitizing effects of STAT3 inhibition in glioma cells. • Dual inhibition of autophagy and STAT3 induce massive apoptotic cells upon exposure to ionizing radiation.

  18. STAT3: A Novel Molecular Mediator of Resistance to Chemoradiotherapy

    PubMed Central

    Spitzner, Melanie; Ebner, Reinhard; Wolff, Hendrik A.; Ghadimi, B. Michael; Wienands, Jürgen; Grade, Marian

    2014-01-01

    Chemoradiotherapy (CRT) represents a standard treatment for many human cancers, frequently combined with radical surgical resection. However, a considerable percentage of primary cancers are at least partially resistant to CRT, which represents a substantial clinical problem, because it exposes cancer patients to the potential side effects of both irradiation and chemotherapy. It is therefore exceedingly important to determine the molecular characteristics underlying CRT-resistance and to identify novel molecular targets that can be manipulated to re-sensitize resistant tumors to CRT. In this review, we highlight much of the recent evidence suggesting that the signal transducer and activator of transcription 3 (STAT3) plays a prominent role in mediating CRT-resistance, and we outline why inhibition of STAT3 holds great promise for future multimodal treatment concepts in oncology. PMID:25268165

  19. Activating STAT3 Alpha for Promoting Healing of Neurons

    NASA Technical Reports Server (NTRS)

    Conway, Greg

    2008-01-01

    A method of promoting healing of injured or diseased neurons involves pharmacological activation of the STAT3 alpha protein. Usually, injured or diseased neurons heal incompletely or not at all for two reasons: (1) they are susceptible to apoptosis (cell death); and (2) they fail to engage in axogenesis that is, they fail to re-extend their axons to their original targets (e.g., muscles or other neurons) because of insufficiency of compounds, denoted neurotrophic factors, needed to stimulate such extension. The present method (see figure) of treatment takes advantage of prior research findings to the effect that the STAT3 alpha protein has anti-apoptotic and pro-axogenic properties.

  20. Constitutive STAT5 Activation Correlates With Better Survival in Cervical Cancer Patients Treated With Radiation Therapy

    SciTech Connect

    Chen, Helen H.W.; Chou, Cheng-Yang; Wu, Yuan-Hua; Hsueh, Wei-Ting; Hsu, Chiung-Hui; Guo, How-Ran; Lee, Wen-Ying; Su, Wu-Chou

    2012-02-01

    Purpose: Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3, and STAT5, have been detected in a wide variety of human primary tumors and have been demonstrated to directly contribute to oncogenesis. However, the expression pattern of these STATs in cervical carcinoma is still unknown, as is whether or not they have prognostic significance. This study investigated the expression patterns of STAT1, STAT3, and STAT5 in cervical cancer and their associations with clinical outcomes in patients treated with radical radiation therapy. Methods and Materials: A total of 165 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) Stages IB to IVA cervical cancer underwent radical radiation therapy, including external beam and/or high-dose-rate brachytherapy between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and to evaluate the effects of these factors affecting patient survival. Results: Constitutive activations of STAT1, STAT3, and STAT5 were observed in 11%, 22%, and 61% of the participants, respectively. While STAT5 activation was associated with significantly better metastasis-free survival (p < 0.01) and overall survival (p = 0.04), STAT1 and STAT3 activation were not. Multivariate analyses showed that STAT5 activation, bulky tumor ({>=}4 cm), advanced stage (FIGO Stages III and IV), and brachytherapy (yes vs. no) were independent prognostic factors for cause-specific overall survival. None of the STATs was associated with local relapse. STAT5 activation (odds ratio = 0.29, 95% confidence interval = 0.13-0.63) and advanced stage (odds ratio = 2.54; 95% confidence interval = 1.03-6.26) were independent predictors of distant metastasis. Conclusions: This is the first report to provide the overall expression patterns and prognostic significance of

  1. SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling

    PubMed Central

    Li, Cong; Li, Hong; Zhang, Peng; Yu, Li-Jun; Huang, Tian-Miao; Song, Xue; Kong, Qing-You; Dong, Jian-Li; Li, Pei-Nan; Liu, Jia

    2016-01-01

    Background: Activated STAT3 signaling is critical for human medulloblastoma cells. SHP2, SOCS3 and PIAS3 are known as the negative regulators of STAT3 signaling, while their relevance to frequent STAT3 activation in medulloblastomas remains unknown. Methods: Tissue microarrays were constructed with 17 tumor-surrounding noncancerous brain tissues and 61 cases of the classic medulloblastomas, 44 the large-cell medulloblastomas, and 15 nodular medulloblastomas, which were used for immunohistochemical profiling of STAT3, SHP2, SOCS3 and PIAS3 expression patterns and the frequencies of STAT3 nuclear translocation. Three human medulloblastoma cell lines (Daoy, UW228-2 and UW228-3) were cultured with and without 100 μM resveratrol supplementation. The influences of resveratrol in SHP2, SOCS3 and PIAS3 expression and SOCS3 knockdown in STAT3 activation were analyzed using multiple experimental approaches. Results: SHP2, SOCS3 and PIAS3 levels are reduced in medulloblastomas in vivo and in vitro, of which PIAS3 downregulation is more reversely correlated with STAT3 activation. In resveratrol-suppressed medulloblastoma cells with STAT3 downregulation and decreased incidence of STAT3 nuclear translocation, PIAS3 is upregulated, the SHP2 level remains unchanged and SOCS3 is downregulated. SOCS3 proteins are accumulated in the distal ends of axon-like processes of resveratrol-differentiated medulloblastoma cells. Knockdown of SOCS3 expression by siRNA neither influences cell proliferation nor STAT3 activation or resveratrol sensitivity but inhibits resveratrol-induced axon-like process formation. Conclusion: Our results suggest that (1) the overall reduction of SHP2, SOCS3 and PIAS3 in medulloblastoma tissues and cell lines; (2) the more inverse relevance of PIAS3 expression with STAT3 activation; (3) the favorable prognostic values of PIAS3 for medulloblastomas and (4) the involvement of SOCS3 in resveratrol-promoted axon regeneration of medulloblastoma cells. PMID:28035977

  2. Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion and can be diagnosed by nuclear expression of STAT6 protein.

    PubMed

    Schweizer, Leonille; Koelsche, Christian; Sahm, Felix; Piro, Rosario M; Capper, David; Reuss, David E; Pusch, Stefan; Habel, Antje; Meyer, Jochen; Göck, Tanja; Jones, David T W; Mawrin, Christian; Schittenhelm, Jens; Becker, Albert; Heim, Stephanie; Simon, Matthias; Herold-Mende, Christel; Mechtersheimer, Gunhild; Paulus, Werner; König, Rainer; Wiestler, Otmar D; Pfister, Stefan M; von Deimling, Andreas

    2013-05-01

    Non-central nervous system hemangiopericytoma (HPC) and solitary fibrous tumor (SFT) are considered by pathologists as two variants of a single tumor entity now subsumed under the entity SFT. Recent detection of frequent NAB2-STAT6 fusions in both, HPC and SFT, provided additional support for this view. On the other hand, current neuropathological practice still distinguishes between HPC and SFT. The present study set out to identify genes involved in the formation of meningeal HPC. We performed exome sequencing and detected the NAB2-STAT6 fusion in DNA of 8/10 meningeal HPC thereby providing evidence of close relationship of these tumors with peripheral SFT. Due to the considerable effort required for exome sequencing, we sought to explore surrogate markers for the NAB2-STAT6 fusion protein. We adopted the Duolink proximity ligation assay and demonstrated the presence of NAB2-STAT6 fusion protein in 17/17 HPC and the absence in 15/15 meningiomas. More practical, presence of the NAB2-STAT6 fusion protein resulted in a strong nuclear signal in STAT6 immunohistochemistry. The nuclear reallocation of STAT6 was detected in 35/37 meningeal HPC and 25/25 meningeal SFT but not in 87 meningiomas representing the most important differential diagnosis. Tissues not harboring the NAB2-STAT6 fusion protein presented with nuclear expression of NAB2 and cytoplasmic expression of STAT6 proteins. In conclusion, we provide strong evidence for meningeal HPC and SFT to constitute variants of a single entity which is defined by NAB2-STAT6 fusion. In addition, we demonstrate that this fusion can be rapidly detected by STAT6 immunohistochemistry which shows a consistent nuclear reallocation. This immunohistochemical assay may prove valuable for the differentiation of HPC and SFT from other mesenchymal neoplasms.

  3. Expression and Activation of STAT Transcription Factors in Breast Cancer

    DTIC Science & Technology

    1998-05-08

    several other studies suggest that estrogen given in low doses to relieve menopausal symptoms probably does not increase the incidence of breast cancer...breast cancer. ’It was recently demonstrated that, while .overall STAT DNA-bindinq activity is low in normal breast and benign lesions, it is...adjuvant anticancer treatment, particularly in chronic myelogenous leukemia, maliqnant melanoma, low · grade lymphoma, multiple myeloma, and midgut

  4. FastStats: a public health statistics database.

    PubMed

    Vardell, Emily

    2014-01-01

    FastStats is a site that provides quick and easy access to public health statistics. The freely available website is maintained by the Centers for Disease Control and Prevention's National Center for Health Statistics. Users can browse alphabetically by topic and state/territory or search across the National Center for Health Statistics site. A description of the browsing capabilities and sample searches are presented.

  5. Automatic electrochemical micro-pH-stat for biomicrosystems.

    PubMed

    Morimoto, Katsuya; Toya, Mariko; Fukuda, Junji; Suzuki, Hiroaki

    2008-02-15

    A microelectrochemical pH-stat with an automatic feedback function was fabricated. The operation of the device is based on the nonstandard use of an electrochemical three-electrode system with a pH-sensitive reference electrode, a Ag/AgCl working electrode, and an iridium auxiliary electrode that functions as an actuator to adjust the solution pH. The combination of the electrodes caused a negative feedback in response to a pH change. The shift of the potential of the pH-sensitive reference electrode caused an overpotential on the Ag/AgCl working electrode, which then caused a significant current increase. This led to the electrolysis of water on the auxiliary electrode and the rapid recovery of the pH. The negative feedback function to stabilize the initial state could be confirmed for changes to both the acidic and basic directions. The performance of the pH-stat was characterized in the titration of acetic acid or ammonia. The charge generated in the feedback process changed linearly with respect to the concentration. The pH-stat was also used in the determination of urea by urease and that of the activities of trypsin and pepsin while maintaining the optimum pH for the enzymes. The pH to be fixed could be changed by changing the working electrode potential. Moreover, the two pH-stats could be used to form a pH gradient in a microflow channel by fixing the pH values at two positions.

  6. IL-17 induces EMT via Stat3 in lung adenocarcinoma

    PubMed Central

    Huang, Qi; Han, Jieli; Fan, Jinshuo; Duan, Limin; Guo, Mengfei; Lv, Zhilei; Hu, Guorong; Chen, Lian; Wu, Feng; Tao, Xiaonan; Xu, Juanjuan; Jin, Yang

    2016-01-01

    Epithelial-mesenchymal transition (EMT) plays a vital role in lung inflammatory diseases, including lung cancer. However, the role and mechanism of action of the proinflammatory cytokine IL-17 in EMT in lung adenocarcinoma remain unresolved. In our study, we discovered that the expression of N-cadherin, Vimentin, Snail1, Snail2, and Twist1 was positively correlated with IL-17 expression, while E-cadherin expression was negatively correlated with IL-17 expression in human lung adenocarcinoma tissues. Moreover, we confirmed that IL-17 promoted EMT in A549 and Lewis lung carcinoma (LLC) cells in vitro by upregulating N-cadherin, Vimentin, Snail1, Snail2, and Twist1 expression and downregulating E-cadherin expression. Stat3 was activated in IL-17-treated A549 and LLC cells, and Stat3 inhibition or siRNA knockdown notably reduced IL-17-induced EMT in A549 and LLC cells. Thus, IL-17 promotes EMT in lung adenocarcinoma via Stat3 signaling; these observations suggest that targeting IL-17 and EMT are potential novel therapeutic strategies for lung cancer. PMID:27186414

  7. StatsCasts: screencasts for complementing lectures in statistics classes

    NASA Astrophysics Data System (ADS)

    Dunn, Peter K.; McDonald, Christine; Loch, Birgit

    2015-05-01

    Students who are studying introductory statistics units but are enrolled in non-statistics majors often struggle with the content, and do not stay engaged. Support structures are in place at many Australian universities to help these students. Most of these are face-to-face support centres that the students can visit during opening hours. To provide additional assistance to these students any time, and from anywhere, online media are increasingly used by students - either provided by support centres, or sought independently by students. Little research has been undertaken on the effectiveness of such resources to support student learning. This paper investigates whether students will embrace StatsCasts - short screen-capture videos on key statistical topics that students have struggled with in the past, with narrator explanation provided by the lecturer - as part of their learning strategy and if they will actively engage with the videos. Students enrolled in a large first-year statistics class at an Australian university who had been provided with StatsCasts responded to a survey at the end of the semester. Volunteering students also participated in a focus group to probe deeper into students' perceptions of and motivations for watching the videos. Analysis of the data shows that students do actively engage with the StatsCasts and they appear to become an important component of their study and revision strategy.

  8. Surface-enhanced Raman scattering spectra of tomato epidermis on gold/ silver sol active substrate

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Chen, Zhenyi; Chen, Na; Hu, Ling; Zhu, Hongfei; Liu, Shupeng; Guo, Qiang

    2011-12-01

    In this paper, tomato epidermis' surface-enhanced Raman scattering spectra were measured on gold and silver active substrates and analyzed. Preparing and using gold sol and silver sol in similar particle diameters (about 50-60nm), three comparable Raman spectra were obtained. Silver sol and gold sol can both increase Raman scattering signal of tomato epidermis. Through the Raman spectra, silver sol has greater enhancement ability than gold sol to tomato epidermis.

  9. Opportunity's Surroundings After Sol 1820 Drive (Stereo)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    [figure removed for brevity, see original site] Left-eye view of a color stereo pair for PIA11841 [figure removed for brevity, see original site] Right-eye view of a color stereo pair for PIA11841

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,820th to 1,822nd Martian days, or sols, of Opportunity's surface mission (March 7 to 9, 2009).

    This view combines images from the left-eye and right-eye sides of the navigation camera. It appears three-dimensional when viewed through red-blue glasses with the red lens on the left.

    The rover had driven 20.6 meters toward the northwest on Sol 1820 before beginning to take the frames in this view. Tracks from that drive recede southwestward. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches).

    The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and small exposures of lighter-toned bedrock.

    This view is presented as a cylindrical-perspective projection with geometric seam correction.

  10. Opportunity's Surroundings on Sol 1798 (Stereo)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    [figure removed for brevity, see original site] Left-eye view of a color stereo pair for PIA11850 [figure removed for brevity, see original site] Right-eye view of a color stereo pair for PIA11850

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this stereo 180-degree view of the rover's surroundings during the 1,798th Martian day, or sol, of Opportunity's surface mission (Feb. 13, 2009). North is on top.

    This view combines images from the left-eye and right-eye sides of the navigation camera. It appears three-dimensional when viewed through red-blue glasses with the red lens on the left.

    The rover had driven 111 meters (364 feet) southward on the preceding sol. Tracks from that drive recede northward in this view. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches).

    The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock.

    This view is presented as a cylindrical-perspective projection with geometric seam correction.

  11. Opportunity's Surroundings on Sol 1818 (Stereo)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    [figure removed for brevity, see original site] Left-eye view of a color stereo pair for PIA11846 [figure removed for brevity, see original site] Right-eye view of a color stereo pair for PIA11846

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,818th Martian day, or sol, of Opportunity's surface mission (March 5, 2009). South is at the center; north at both ends.

    This view combines images from the left-eye and right-eye sides of the navigation camera. It appears three-dimensional when viewed through red-blue glasses with the red lens on the left.

    The rover had driven 80.3 meters (263 feet) southward earlier on that sol. Tracks from the drive recede northward in this view.

    The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock.

    This view is presented as a cylindrical-perspective projection with geometric seam correction.

  12. Spirit View of Phobos Eclipse, Sol 675

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Annotated Spirit View of Phobos Eclipse, Sol 675

    NASA's Mars Exploration Rover Spirit observed the Martian moon Phobos entering the shadow of Mars during the night of the rover's 675th sol (Nov. 27, 2005). The panoramic camera captured 16 images, spaced 10 seconds apart, covering the period from when Phobos was in full sunlight to when it was entirely in shadow. As with our own Moon during lunar eclipses on Earth, even when in the planet's shadow, Phobos was not entirely dark. The small amount of light still visible from Phobos is a kind of 'Mars-shine' -- sunlight reflected through Mars' atmosphere and into the shadowed region.

    This view is a time-lapse composite of images taken 20 seconds apart, showing the movement of Phobos from left to right. (At 10 seconds apart, the images of the moon overlap each other.) Scientists are using information about the precise timing of Martian moon eclipses gained from observations such as these to refine calculations about the orbital path of Phobos. The precise position of Phobos will be important to any future spacecraft taking detailed pictures of the moon or landing on its surface.

  13. After Sample-Delivery Attempt, Sol 62

    NASA Technical Reports Server (NTRS)

    2008-01-01

    NASA's Phoenix Mars Lander collected a soil sample and attempted to deliver some of it to a laboratory oven on the deck during the mission's 62nd Martian day, or sol, (July 28, 2008). The sample came from a hard layer at the bottom of the 'Snow White' trench and might have contained water ice mixed with the soil. This image taken after the attempt to deliver the sample through the open doors to cell number zero on the Thermal and Evolved-Gas Analyzer shows that very little of the soil fell onto the screened opening.

    Not enough material reached the oven, through a funnel under the screen, to proceed with analysis of the sample material.

    Phoenix's Robotic Arm Camera took this image at 7:54 a.m. local solar time on Sol 62. The size of the screened opening is about 10 centimeters (4 inches) long by 4 centimeters (1.5 inches) wide.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  14. Solar sanitary system (SOL-SAN)

    SciTech Connect

    Cobb, J.C.

    1996-11-01

    Ordinary composting toilets, because of cooling by evaporation, do not heat the product (humus) hot enough to kill all pathogenic viruses, bacteria, or parasite eggs and cysts. The SOL-SAN system uses direct radiation to pasteurize incoming river water for drinking and also, separately, to pasteurize and dry the humus, and to pasteurize the effluent gray/brown water. Work is in progress on simple fool-proof methods of insuring that the water will not flow out unless it has been pasteurized. Heat exchangers recapture the heat from these very hot pasteurized liquids, thereby warming more in-coming water for washing, which is important for preventing transmission of pathogenic microbes. When pasteurized, the humus and gray/brown water can safely be recycled to fertilize and water the family vegetable garden. Thus no sewer would be needed, and the vegetables or fish would grow well. Widespread use of the SOL-SAN system would save water and nutrients, reduce the prevalence of infectious diseases, improve the nutrition and vitality of the population, and save the large fraction of human food now consumed by parasites.

  15. Opportunity's Heat Shield in Color, Sol 325

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This image from the panoramic camera on NASA's Mars Exploration Rover Opportunity shows remains of the heat shield that protected the spacecraft as it barreled through the martian atmosphere. The image was taken on the rover's 325th martian day, or sol, (Dec. 22, 2004).

    The picture features the main heat shield debris when Opportunity was approximately 40 meters (about 131 feet) away from it. Many rover-team engineers were taken aback when they realized the heat shield had inverted, or turned itself inside out. The height of the pictured debris is about 1.3 meters (about 4.3 feet). The original diameter was 2.65 meters (8.7 feet), though it has obviously been deformed.

    The fact that the heat shield is now inside out makes it more challenging to evaluate the state of the thermal protection system that is now on the inside. In coming sols, Opportunity will investigate the debris with its microscopic imager.

    Engineers who designed and built the heat shield are thrilled to see the hardware on the surface of Mars. This provides a unique opportunity to look at how the thermal protection system material survived the actual Mars entry. Team members hope this information will allow them to compare their predictions to what really happened.

    The image is an approximately true-color rendering generated using the panoramic camera's 600, 530 and 480 nanometer filters.

  16. View Ahead After Spirit's Sol 1861 Drive

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Spirit used its navigation camera to take the images combined into this 210-degree view of the rover's surroundings during the 1,861st to 1,863rd Martian days, or sols, of Spirit's surface mission (March 28 to 30, 2009).

    The center of the scene is toward the south-southwest. East is on the left. West-northwest is on the right.

    The rover had driven 22.7 meters (74 feet) southwestward on Sol 1861 before beginning to take the frames in this view. The drive brought Spirit past the northwestern corner of Home Plate.

    In this view, the western edge of Home Plate is on the portion of the horizon farthest to the left. A mound in middle distance near the center of the view is called 'Tsiolkovsky' and is about 40 meters (about 130 feet) from the rover's position.

    This view is presented as a cylindrical projection with geometric seam correction.

  17. Spirit Beside 'Home Plate,' Sol 1809 (Stereo)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    [figure removed for brevity, see original site] Left-eye view of a color stereo pair for PIA11803 [figure removed for brevity, see original site] Right-eye view of a color stereo pair for PIA11803

    NASA Mars Exploration Rover Spirit used its navigation camera to take the images assembled into this stereo, 120-degree view southward after a short drive during the 1,809th Martian day, or sol, of Spirit's mission on the surface of Mars (February 3, 2009).

    By combining images from the left-eye and right-eye sides of the navigation camera, the view appears three-dimensional when viewed through red-blue glasses with the red lens on the left.

    Spirit had driven about 2.6 meters (8.5 feet) that sol, continuing a clockwise route around a low plateau called 'Home Plate.' In this image, the rocks visible above the rovers' solar panels are on the slope at the northern edge of Home Plate.

    This view is presented as a cylindrical-perspective projection with geometric seam correction.

  18. Sol-gel precursors and products thereof

    DOEpatents

    Warren, Scott C.; DiSalvo, Jr., Francis J.; Weisner, Ulrich B.

    2017-02-14

    The present invention provides a generalizable single-source sol-gel precursor capable of introducing a wide range of functionalities to metal oxides such as silica. The sol-gel precursor facilitates a one-molecule, one-step approach to the synthesis of metal-silica hybrids with combinations of biological, catalytic, magnetic, and optical functionalities. The single-source precursor also provides a flexible route for simultaneously incorporating functional species of many different types. The ligands employed for functionalizing the metal oxides are derived from a library of amino acids, hydroxy acids, or peptides and a silicon alkoxide, allowing many biological functionalities to be built into silica hybrids. The ligands can coordinate with a wide range of metals via a carboxylic acid, thereby allowing direct incorporation of inorganic functionalities from across the periodic table. Using the single-source precursor a wide range of functionalized nanostructures such as monolith structures, mesostructures, multiple metal gradient mesostructures and Stober-type nanoparticles can be synthesized. ##STR00001##

  19. A new biocatalyst: Penicillin G acylase immobilized in sol-gel micro-particles with magnetic properties.

    PubMed

    Bernardino, Susana M S A; Fernandes, Pedro; Fonseca, Luís P

    2009-05-01

    The present work focuses on the development and basic characterization of a new magnetic biocatalyst, namely penicillin G acylase (PGA), immobilized in sol-gel matrices with magnetic properties, ultimately aimed for application in cephalexin (CEX) synthesis. A mechanically stable carrier, based on porous xerogels silica matrixes starting from tetramethoxysilane (TMOS), was prepared leading to micro-carriers with medium sized particles of 30 microm, as determined by scanning electron microscopy. An immobilization yield of 95-100% and a recovered activity of 50-65% at 37 degrees C, as determined by penicillin G (PG) hydrolysis (pH STAT method), were observed. These results clearly exceed those reported in a previous work on PGA immobilization in sol-gel, where only 10% of activity was recovered. The values of activity were kept constant for 6 months. Immobilized PGA (682 U/g(dry weight)) retained high specific activity throughout ten consecutive runs for PG hydrolysis, suggesting adequate biocatalyst stability. The CEX synthesis was performed at 14 degrees C, using the free and immobilized PGA in aqueous medium. Phenylglycine methyl ester was used as acyl donor at 90 mM and 7-aminodeacetoxycephalosporanic acid was the limiting substrate at 30 mM. The CEX stoichiometric yield after 1-h reaction was close to 68% (23 mM CEX/h) and 65% (19 mM CEX/h), respectively.

  20. Interim Guidance on the Use of SiteStat/GridStats and Other Army Corps of Engineers Statistical Techniques to Characterize Military Ranges

    EPA Pesticide Factsheets

    The purpose of this memorandum is to inform recipients of concerns regarding Army Corps of Engineers statistical techniques, provide a list of installations and FWS where SiteStat/GridStats (SS/GS) have been used, and to provide direction on communicating with the public on the use of these 'tools' by USACE.

  1. Application of the docking program SOL for CSAR benchmark.

    PubMed

    Sulimov, Alexey V; Kutov, Danil C; Oferkin, Igor V; Katkova, Ekaterina V; Sulimov, Vladimir B

    2013-08-26

    This paper is devoted to results obtained by the docking program SOL and the post-processing program DISCORE at the CSAR benchmark. SOL and DISCORE programs are described. SOL is the original docking program developed on the basis of the genetic algorithm, MMFF94 force field, rigid protein, precalculated energy grid including desolvation in the frame of simplified GB model, vdW, and electrostatic interactions and taking into account the ligand internal strain energy. An important SOL feature is the single- or multi-processor performance for up to hundreds of CPUs. DISCORE improves the binding energy scoring by the local energy optimization of the ligand docked pose and a simple linear regression on the base of available experimental data. The docking program SOL has demonstrated a good ability for correct ligand positioning in the active sites of the tested proteins in most cases of CSAR exercises. SOL and DISCORE have not demonstrated very exciting results on the protein-ligand binding free energy estimation. Nevertheless, for some target proteins, SOL and DISCORE were among the first in prediction of inhibition activity. Ways to improve SOL and DISCORE are discussed.

  2. Biocatalysis with Sol-Gel Encapsulated Acid Phosphatase

    ERIC Educational Resources Information Center

    Kulkarni, Suhasini; Tran, Vu; Ho, Maggie K.-M.; Phan, Chieu; Chin, Elizabeth; Wemmer, Zeke; Sommerhalter, Monika

    2010-01-01

    This experiment was performed in an upper-level undergraduate biochemistry laboratory course. Students learned how to immobilize an enzyme in a sol-gel matrix and how to perform and evaluate enzyme-activity measurements. The enzyme acid phosphatase (APase) from wheat germ was encapsulated in sol-gel beads that were prepared from the precursor…

  3. The evolutionary divergence of STAT transcription factor in different Anopheles species.

    PubMed

    Gupta, Kuldeep; Dhawan, Rini; Kajla, Mithilesh; Misra, Tripti; Kumar, Sanjeev; Gupta, Lalita

    2017-01-05

    Anopheles mosquito transmits Plasmodium, the malaria causing parasite. Different species of Anopheles mosquito dominate in a particular geographical location and are capable of transmitting specific strains of Plasmodium. It is important to understand the biology of different anophelines to control the parasite transmission. STAT is an evolutionary conserved transcription factor that regulates the parasite development in African malaria vector Anopheles gambiae. Unlike Drosophila and Aedes aegypti, where a single STAT gene plays an important role in immunity, An. gambiae contains one evolutionary conserved STAT-A and another retro-duplicated, introns-less STAT-B gene. To find out whether other species of Anopheles also have two STATs, the available genomic data of different anophelines were used to annotate their STATs through in silico analyses. Our results revealed that Indian malaria vector An. stephensi genome contains two STATs, AsSTAT-A and AsSTAT-B genes. These genes were cloned and confirmed by sequencing. Both AsSTATs were found to be expressed in different development stages of mosquito. However, the relative mRNA levels of evolutionary conserved AsSTAT-A gene were always higher than the retroduplicated AsSTAT-B gene. STAT pathway was activated upon Plasmodium berghei infection, indicated its role in immunity. Furthermore, comparative in silico analysis of eighteen Anopheles species revealed that five species: An. sinensis, An. albimanus, An. darlingi, An. dirus andAn. farauti do not contain STAT-B gene in their genome. Interestingly, thirteen species of the subgenus Anopheles and Cellia that contain both STATs were also mutually diverged. This consequence leads to sequence variability in some significant protein motifs within the STAT-B genes. Phylogenetic analyses indicated that an independent, lineage-specific duplication occurred in the subgenus Cellia after the diversification of series Neomyzomyia from its last common ancestor. In An. atroparvus

  4. High-Content pSTAT3/1 Imaging Assays to Screen for Selective Inhibitors of STAT3 Pathway Activation in Head and Neck Cancer Cell Lines

    PubMed Central

    Sen, Malabika; Hua, Yun; Camarco, Daniel; Shun, Tong Ying; Lazo, John S.; Grandis, Jennifer R.

    2014-01-01

    Abstract The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is hyperactivated in most cancers and represents a plausible therapeutic target. In the absence of STAT3-selective small-molecule inhibitors, we sought to develop pSTAT3/1 high-content imaging (HCS) assays to screen for selective inhibitors of STAT3 pathway activation in head and neck squamous cell carcinomas (HNSCC) tumor cell lines. Based on the expression of the interleukin-6 (IL-6)Rα and gp130 subunits of the IL-6 receptor complex and STAT3, we selected the Cal33 HNSCC cell line as our model. After developing image acquisition and analysis procedures, we rigorously investigated the cytokine activation responses to optimize the dynamic ranges of both assays and demonstrated that the pan-Janus kinase inhibitor pyridone 6 nonselectively inhibited pSTAT3 and pSTAT1 activation with 50% inhibition concentrations of 7.19±4.08 and 16.38±8.45 nM, respectively. The optimized pSTAT3 HCS assay performed very well in a pilot screen of 1,726 compounds from the Library of Pharmacologically Active Compounds and the National Institutes of Health clinical collection sets, and we identified 51 inhibitors of IL-6-induced pSTAT3 activation. However, only three of the primary HCS actives selectively inhibited STAT3 compared with STAT1. Our follow-up studies indicated that the nonselective inhibition of cytokine induced pSTAT3 and pSTAT1 activation by G-alpha stimulatory subunit-coupled G-protein-coupled receptor agonists, and forskolin was likely due to cyclic adenosine monophosphate-mediated up-regulation of suppressors of cytokine signaling 3. Azelastine, an H1 receptor antagonist approved for the treatment of seasonal allergic rhinitis, nonallergic vasomotor rhinitis, and ocular conjunctivitis, was subsequently confirmed as a selective inhibitor of IL-6-induced pSTAT3 activation that also reduced the growth of HNSCC cell lines. These data illustrate the power of a chemical

  5. Human Cytomegalovirus Immediate-Early 1 Protein Rewires Upstream STAT3 to Downstream STAT1 Signaling Switching an IL6-Type to an IFNγ-Like Response

    PubMed Central

    Lukas, Simone; Zenger, Marion; Reitberger, Tobias; Danzer, Daniela; Übner, Theresa; Munday, Diane C.; Paulus, Christina

    2016-01-01

    The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication. PMID:27387064

  6. The measles virus phosphoprotein interacts with the linker domain of STAT1

    SciTech Connect

    Devaux, Patricia Priniski, Lauren; Cattaneo, Roberto

    2013-09-15

    The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway. - Highlights: • Residue in the linker and SH2 domains of STAT1 are important for MV-P interaction. • Residue in the linker and SH2 domains of STAT1 are important for STAT1 phosphorylation. • Residues interferring with both functions have similar location on STAT1. • The viral P and V proteins may operate in concert to inhibit the JAK/STAT pathway.

  7. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing.

    PubMed

    Pickert, Geethanjali; Neufert, Clemens; Leppkes, Moritz; Zheng, Yan; Wittkopf, Nadine; Warntjen, Moritz; Lehr, Hans-Anton; Hirth, Sebastian; Weigmann, Benno; Wirtz, Stefan; Ouyang, Wenjun; Neurath, Markus F; Becker, Christoph

    2009-07-06

    Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c(+) cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific deletion of STAT3 activity were highly susceptible to experimental colitis, indicating that epithelial STAT3 regulates gut homeostasis. STAT3(IEC-KO) mice, upon induction of colitis, showed a striking defect of epithelial restitution. Gene chip analysis indicated that STAT3 regulates the cellular stress response, apoptosis, and pathways associated with wound healing in IECs. Consistently, both IL-22 and epithelial STAT3 were found to be important in wound-healing experiments in vivo. In summary, our data suggest that intestinal epithelial STAT3 activation regulates immune homeostasis in the gut by promoting IL-22-dependent mucosal wound healing.

  8. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing

    PubMed Central

    Pickert, Geethanjali; Neufert, Clemens; Leppkes, Moritz; Zheng, Yan; Wittkopf, Nadine; Warntjen, Moritz; Lehr, Hans-Anton; Hirth, Sebastian; Weigmann, Benno; Wirtz, Stefan; Ouyang, Wenjun; Neurath, Markus F.

    2009-01-01

    Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c+ cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific deletion of STAT3 activity were highly susceptible to experimental colitis, indicating that epithelial STAT3 regulates gut homeostasis. STAT3IEC-KO mice, upon induction of colitis, showed a striking defect of epithelial restitution. Gene chip analysis indicated that STAT3 regulates the cellular stress response, apoptosis, and pathways associated with wound healing in IECs. Consistently, both IL-22 and epithelial STAT3 were found to be important in wound-healing experiments in vivo. In summary, our data suggest that intestinal epithelial STAT3 activation regulates immune homeostasis in the gut by promoting IL-22–dependent mucosal wound healing. PMID:19564350

  9. Myeloid STAT3 promotes formation of colitis-associated colorectal cancer in mice

    PubMed Central

    Pathria, Paulina; Gotthardt, Dagmar; Prchal-Murphy, Michaela; Putz, Eva-Maria; Holcmann, Martin; Schlederer, Michaela; Grabner, Beatrice; Crncec, Ilija; Svinka, Jasmin; Musteanu, Monica; Hoffmann, Thomas; Filipits, Martin; Berger, Walter; Poli, Valeria; Kenner, Lukas; Bilban, Martin; Casanova, Emilio; Müller, Mathias; Strobl, Birgit; Bayer, Editha; Mohr, Thomas; Sexl, Veronika; Eferl, Robert

    2015-01-01

    Myeloid cells lacking STAT3 promote antitumor responses of NK and T cells but it is unknown if this crosstalk affects development of autochthonous tumors. We deleted STAT3 in murine myeloid cells (STAT3Δm) and examined the effect on the development of autochthonous colorectal cancers (CRCs). Formation of Azoxymethane/Dextransulfate (AOM/DSS)-induced CRCs was strongly suppressed in STAT3Δm mice. Gene expression profiling showed strong activation of T cells in the stroma of STAT3Δm CRCs. Moreover, STAT3Δm host mice were better able to control the growth of transplanted MC38 colorectal tumor cells which are known to be killed in a T cell-dependent manner. These data suggest that myeloid cells lacking STAT3 control formation of CRCs mainly via cross activation of T cells. Interestingly, the few CRCs that formed in STAT3Δm mice displayed enhanced stromalization but appeared normal in size indicating that they have acquired ways to escape enhanced tumor surveillance. We found that CRCs in STAT3Δm mice consistently activate STAT3 signaling which is implicated in immune evasion and might be a target to prevent tumor relapse. PMID:26137415

  10. Mechanisms of STAT3 activation in the liver of FXR knockout mice

    PubMed Central

    Li, Guodong; Zhu, Yan; Tawfik, Ossama; Kong, Bo; Williams, Jessica A.; Zhan, Le; Kassel, Karen M.; Luyendyk, James P.; Wang, Li

    2013-01-01

    Farnesoid X receptor (FXR, Nr1h4) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. FXR is essential in maintaining bile acid (BA) homeostasis, and FXR−/− mice develop cholestasis, inflammation, and spontaneous liver tumors. The signal transducer and activator of transcription 3 (STAT3) is well known to regulate liver growth, and STAT3 is feedback inhibited by its target gene, the suppressor of cytokine signaling 3 (SOCS3). Strong activation of STAT3 was detected in FXR−/− mouse livers. However, the mechanism of STAT3 activation with FXR deficiency remains elusive. Wild-type (WT) and FXR−/− mice were used to detect STAT3 pathway activation in the liver. In vivo BA feeding or deprivation was used to determine the role of BAs in STAT3 activation, and in vitro molecular approaches were used to determine the direct transcriptional regulation of SOCS3 by FXR. STAT3 was activated in FXR−/− but not WT mice. BA feeding increased, but deprivation by cholestyramine reduced, serum inflammatory markers and STAT3 activation. Furthermore, the Socs3 gene was determined as a direct FXR target gene. The elevated BAs and inflammation, along with reduced SOCS3, collectively contribute to the activation of the STAT3 signaling pathway in the liver of FXR−/− mice. This study suggests that the constitutive activation of STAT3 may be a mechanism of liver carcinogenesis in FXR−/− mice. PMID:24091600

  11. STAT3 Inhibition by Microtubule-Targeted Drugs: Dual Molecular Effects of Chemotherapeutic Agents

    PubMed Central

    Walker, Sarah R.; Chaudhury, Mousumi; Frank, David A.

    2011-01-01

    To improve the effectiveness of anti-cancer therapies, it is necessary to identify molecular targets that are essential to a tumor cell but dispensable in a normal cell. Increasing evidence indicates that the transcription factor STAT3, which regulates the expression of genes controlling proliferation, survival, and self-renewal, constitutes such a target. Recently it has been found that STAT3 can associate with the cytoskeleton. Since many of the tumors in which STAT3 is activated, such as breast cancer and ovarian cancer, are responsive to drugs that target microtubules, we examined the effect of these compounds on STAT3. We found that microtubule stabilizers, such as paclitaxel, or microtubule inhibitors, such as vinorelbine, decrease the activating tyrosine phosphorylation of STAT3 in tumor cells and inhibit the expression of STAT3 target genes. Paclitaxel decreases the association between STAT3 and microtubules, and appears to decrease STAT3 phosphorylation through induction of a negative feedback regulator. The cytotoxic activity of paclitaxel in breast cancer cell lines correlates with its ability to decrease STAT3 phosphorylation. However, consistent with the necessity for expression of a negative regulator, treatment of resistant MDA-MB-231 cells with the DNA demethylating agent 5-azacytidine restores the ability of paclitaxel to block STAT3-dependent gene expression. Finally, the combination of paclitaxel and agents that directly target STAT3 has beneficial effects in killing STAT3-dependent cell lines. Thus, microtubule-targeted agents may exert some of their effects by inhibiting STAT3, and understanding this interaction may be important for optimizing rational targeted cancer therapies. PMID:21949561

  12. LIGHT, a member of the TNF superfamily, activates Stat3 mediated by NIK pathway

    SciTech Connect

    Nadiminty, Nagalakshmi; Chun, Jae Yeon; Hu, Yan; Dutt, Smitha; Lin, Xin; Gao, Allen C. . E-mail: allen.gao@roswellpark.org

    2007-07-27

    Stat3, a member of the signal transducers and activators of transcription (STAT) family, is a key signal transduction protein activated by numerous cytokines, growth factors, and oncoproteins that controls cell proliferation, differentiation, development, survival, and inflammation. Constitutive activation of Stat3 has been found frequently in a wide variety of human tumors and induces cellular transformation and tumor formation. In this study, we demonstrated that LIGHT, a member of tumor necrosis factor superfamily, activates Stat3 in cancer cells. LIGHT induces dose-dependent activation of Stat3 by phosphorylation at both the tyrosine 705 and serine 727 residues. The activation of Stat3 by LIGHT appears to be mediated by NIK phosphorylation. Expression of a kinase-inactive NIK mutant abolished LIGHT induced Stat3 activation. Overexpression of an active NIK induces Stat3 activation by phosphorylation at the both tyrosine 705 and serine 727 residues. Activation of Stat3 by NIK requires NIK kinase activity as showed by kinase assays. In addition, LIGHT increases the expression of Stat3 target genes including cyclin D1, survivin, and Bcl-xL, and stimulates human LNCaP prostate cancer cell growth in vitro which can be blocked by expression of a dominant-negative Stat3 mutant. Taken together, these results indicate that in addition to activating NF-{kappa}B/p52, LIGHT also activates Stat3. Activation of Stat3 together with activating non-canonical NF-{kappa}B/p52 signaling by LIGHT may maximize its effects on cellular proliferation, survival, and inflammation.

  13. Stat5a increases lactation of dairy cow mammary gland epithelial cells cultured in vitro.

    PubMed

    Liu, Xiao Fei; Li, Meng; Li, Qing Zhang; Lu, Li Min; Tong, Hui Li; Gao, Xue Jun

    2012-10-01

    Signal transducer and activator of transcription 5a (Stat5a) transduces signals of extracellular cytokines and growth factors to the nucleus of mammary gland epithelial cells and thereby regulates gene transcription during pregnancy, lactation, and weaning. However, its function on the milk production of dairy cows needs further investigation. In this experiment, the effects of Stat5a on lactation ability of dairy cow mammary gland epithelial cells (DCMECs) were analyzed. Eukaryotic expression vector pcDNA3.1+-stat5a-αS1 was constructed by inserting stat5a gene into the plasmid vector pcDNA3.1+ and replacing CMV promoter with α-S1-casein 5' flanking sequence. The recombinant vector was stably transfected into DCMECs after geneticin (G418) selection. The proliferation and viability of DCMECs, expression of β-casein and stat5a gene, and the content of lactose were detected. The results showed that stat5a gene in eukaryotic expression vector pcDNA3.1+-stat5a-αS1 was highly expressed in DCMECs and could increase the lactation ability of DCMECs. The associativity of Stat5a with nutrients on the lactation ability of DCMECs was also evaluated. Lysine (Lys), methionine (Met), sodium acetate, β-sodium hydroxybutyrate, and glucose all had more positive effects on the lactation function of DCMECs after pcDNA3.1+-stat5a-αS1 transfection. The proliferation and viability of DCMECs, expression of β-casein and stat5a gene, and contents of lactose and triglyceride were detected. The results revealed that nutrients could promote expression of Stat5a gene to increase lactation of DCMECs. These data help to clarify the function of stat5 gene on lactation and gene regulatory networks linking stat5a.

  14. Tannic acid inhibits EGFR/STAT1/3 and enhances p38/STAT1 signalling axis in breast cancer cells.

    PubMed

    Darvin, Pramod; Joung, Youn Hee; Kang, Dong Young; Sp, Nipin; Byun, Hyo Joo; Hwang, Tae Sook; Sasidharakurup, Hema; Lee, Chi Ho; Cho, Kwang Hyun; Park, Kyung Do; Lee, Hak Kyo; Yang, Young Mok

    2017-04-01

    Tannic acid (TA), a naturally occurring polyphenol, is a potent anti-oxidant with anti-proliferative effects on multiple cancers. However, its ability to modulate gene-specific expression of tumour suppressor genes and oncogenes has not been assessed. This work investigates the mechanism of TA to regulate canonical and non-canonical STAT pathways to impose the gene-specific induction of G1-arrest and apoptosis. Regardless of the p53 status and membrane receptors, TA induced G1-arrest and apoptosis in breast cancer cells. Tannic acid distinctly modulated both canonical and non-canonical STAT pathways, each with a specific role in TA-induced anti-cancer effects. Tannic acid enhanced STAT1 ser727 phosphorylation via upstream serine kinase p38. This STAT1 ser727 phosphorylation enhanced the DNA-binding activity of STAT1 and in turn enhanced expression of p21(Waf1/Cip1) . However, TA binds to EGF-R and inhibits the tyrosine phosphorylation of both STAT1 and STAT3. This inhibition leads to the inhibition of STAT3/BCL-2 DNA-binding activity. As a result, the expression and mitochondrial localization of BCl-2 are declined. This altered expression and localization of mitochondrial anti-pore factors resulted in the release of cytochrome c and the activation of intrinsic apoptosis cascade involving caspases. Taken together, our results suggest that TA modulates EGF-R/Jak2/STAT1/3 and P38/STAT1/p21(Waf1/Cip1) pathways and induce G1-arrest and intrinsic apoptosis in breast carcinomas.

  15. Onion skin model (OSM) analysis of EAST SOL plasmas

    NASA Astrophysics Data System (ADS)

    Wang, F. Q.; Chen, Y. P.; Hu, L. Q.; Guo, H. Y.; Liu, S. C.; Wang, L.

    2014-09-01

    Two-dimensional maps of the Experimental Advanced Superconducting Tokamak (EAST) scrape-off layer (SOL) plasma conditions for ohmic, L-mode and H-mode discharges are reconstructed using an onion skin model (OSM) coupled in DIVIMP together with the Monte Carlo neutral transport code, EIRENE. The boundary conditions for OSM calculation are taken from the measurements of the Langmuir probe built into the divertor targets. The OSM-calculated values of the outboard mid-plane electron density, ne, and temperature, Te, are compared with the mid-plane measurements of ne and Te from a fast reciprocating probe. Some other characteristics of these SOL plasmas are also derived from the OSM solution, reflecting that the upstream plasma conditions are governed by the SOL collisionality to a large degree. Values of \\chi_{\\bot}^{SOL} at the low-field side and the high-field side mid-plane are derived separately as a function of the distance to the separatrix for ohmic, L- and H-mode discharges, showing that \\chi_{\\bot}^{{SOL}} increases with the distance to the separatrix at both sides and that the values of \\chi_{\\bot}^{SOL} at the low-field side tends to be higher than that at the high-field side. \\chi_{\\bot e}^{SOL} is found to be larger than \\chi_{\\bot i}^{SOL} by a factor of 2-3 for all the discharges considered here. In addition, before the use of the OSM method of extracting \\chi_{\\bot}^{SOL} and D_{\\bot}^{SOL} for EAST discharges, the reliability of this method is assessed by taking SOLPS-generated target n, T profiles as boundary conditions and by comparing the OSM-extracted cross-field transport coefficients with those input in the SOLPS modelling.

  16. Comment on ``Amorphization and defect recombination in ion implanted silicon carbide'' [J. Appl. Phys. 81, 7181 (1997)

    NASA Astrophysics Data System (ADS)

    Heera, V.

    1998-04-01

    It is demonstrated that the simplified analysis of Rutherford backscattering\\channeling data on damage production in SiC performed by Grimaldi et al. [J. Appl. Phys. 81, 7181 (1997)] cannot be used to calculate the atomic displacement energy. The value of 12 eV at which the authors arrive is much too small. Moreover, their conclusion of similar displacement energies in Si and SiC is essentially wrong. The general reasons for that are discussed and illustrated by an example.

  17. Comment on "The physics origin of the hierarchy of bodies in space" [J. Appl. Phys. 119, 094901 (2016)

    NASA Astrophysics Data System (ADS)

    Swartz, C. H.

    2016-09-01

    A recent paper [A. Bejan and R. W. Wagstaff, J. Appl. Phys. 119, 094901 (2016)] concludes that bodies of the same size suspended uniformly in space are in a state of high internal tension. The tension is then relieved by rearrangement of the bodies into a non-uniform distribution of mass. In this Comment, it is shown that the conclusions are based upon calculations which are in error, and that the amount of tension is not in fact decreased by such a rearrangement.

  18. Comment on "Size-efficient metamaterial absorber at low frequencies: Design, fabrication, and characterization" [J. Appl. Phys. 117, 243105 (2015)

    NASA Astrophysics Data System (ADS)

    Liu, Lulu; Liu, Shaobin; Zhang, HaiFeng; Kong, Xiangkun; Yang, Hua; Ding, Guowen; Xu, Ce; Wang, Lingling; Shi, Wei

    2016-06-01

    In a recent article, Khuyen et al. [J. Appl. Phys. 117, 243105 (2015)] proposed a metamaterial perfect absorber (MPA) with a self-asymmetric structure and claimed that it could produce dual-band "perfect absorption." In this report, we demonstrate that the self-asymmetric structure is not a true MPA. The cross-polarization reflection, which is induced by coupling between the induced magnetic field and the incident electric field, is ignored in calculation of absorptivity of that structure. The real absorption rate of this structure is below 60%, which indicates that the structure cannot be called a perfect absorber.

  19. Comment on “On the quantum theory of molecules” [J. Chem. Phys. 137, 22A544 (2012)

    SciTech Connect

    Sutcliffe, Brian T.; Woolley, R. Guy

    2014-01-21

    In our previous paper [B. T. Sutcliffe and R. G. Woolley, J. Chem. Phys. 137, 22A544 (2012)] we argued that the Born-Oppenheimer approximation could not be based on an exact transformation of the molecular Schrödinger equation. In this Comment we suggest that the fundamental reason for the approximate nature of the Born-Oppenheimer model is the lack of a complete set of functions for the electronic space, and the need to describe the continuous spectrum using spectral projection.

  20. Sol-Gel Processing Science Using a Sol-Gel Optics Research Facility (SGORF)

    DTIC Science & Technology

    1989-09-10

    property of the sol-gel process can be used to make optics with special shapes and surface features such as lightweight mirrors, Fresnel lenses and...lightweight mirrors, Fresnel lenses and aspheric optical components.I Acknowledgements The authors gratefully acknowledge financial support of Air Force...e.g. Fresnel lenses ) - internal structures3 - reduced grinding - reduced polishing ! Improved Physical Properties (Type V) - lower coefficient of

  1. Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer.

    PubMed

    Nefedova, Yulia; Huang, Mei; Kusmartsev, Sergei; Bhattacharya, Raka; Cheng, Pingyan; Salup, Raoul; Jove, Richard; Gabrilovich, Dmitry

    2004-01-01

    Abnormal differentiation of myeloid cells is one of the hallmarks of cancer. However, the molecular mechanisms of this process remain elusive. In this study, we investigated the effect of tumor-derived factors on Janus kinase (Jak)/STAT signaling in myeloid cells during their differentiation into dendritic cells. Tumor cell conditioned medium induced activation of Jak2 and STAT3, which was associated with an accumulation of immature myeloid cells. Jak2/STAT3 activity was localized primarily in these myeloid cells, which prevented the differentiation of immature myeloid cells into mature dendritic cells. This differentiation was restored after removal of tumor-derived factors. Inhibition of STAT3 abrogated the negative effects of these factors on myeloid cell differentiation, and overexpression of STAT3 reproduced the effects of tumor-derived factors. Thus, this is a first demonstration that tumor-derived factors may affect myeloid cell differentiation in cancer via constitutive activation of Jak2/STAT3.

  2. Revisiting STAT3 signalling in cancer: new and unexpected biological functions.

    PubMed

    Yu, Hua; Lee, Heehyoung; Herrmann, Andreas; Buettner, Ralf; Jove, Richard

    2014-11-01

    The Janus kinases (JAKs) and signal transducer and activator of transcription (STAT) proteins, particularly STAT3, are among the most promising new targets for cancer therapy. In addition to interleukin-6 (IL-6) and its family members, multiple pathways, including G-protein-coupled receptors (GPCRs), Toll-like receptors (TLRs) and microRNAs were recently identified to regulate JAK-STAT signalling in cancer. Well known for its role in tumour cell proliferation, survival, invasion and immunosuppression, JAK-STAT3 signalling also promotes cancer through inflammation, obesity, stem cells and the pre-metastatic niche. In addition to its established role as a transcription factor in cancer, STAT3 regulates mitochondrion functions, as well as gene expression through epigenetic mechanisms. Newly identified regulators and functions of JAK-STAT3 in tumours are important targets for potential therapeutic strategies in the treatment of cancer.

  3. STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling.

    PubMed

    Arimoto, Kei-Ichiro; Löchte, Sara; Stoner, Samuel A; Burkart, Christoph; Zhang, Yue; Miyauchi, Sayuri; Wilmes, Stephan; Fan, Jun-Bao; Heinisch, Jürgen J; Li, Zhi; Yan, Ming; Pellegrini, Sandra; Colland, Frédéric; Piehler, Jacob; Zhang, Dong-Er

    2017-03-01

    Type I interferons (IFNs) are multifunctional cytokines that regulate immune responses and cellular functions but also can have detrimental effects on human health. A tight regulatory network therefore controls IFN signaling, which in turn may interfere with medical interventions. The JAK-STAT signaling pathway transmits the IFN extracellular signal to the nucleus, thus resulting in alterations in gene expression. STAT2 is a well-known essential and specific positive effector of type I IFN signaling. Here, we report that STAT2 is also a previously unrecognized, crucial component of the USP18-mediated negative-feedback control in both human and mouse cells. We found that STAT2 recruits USP18 to the type I IFN receptor subunit IFNAR2 via its constitutive membrane-distal STAT2-binding site. This mechanistic coupling of effector and negative-feedback functions of STAT2 may provide novel strategies for treatment of IFN-signaling-related human diseases.

  4. EXTENSIVE SURVEY OF STAT6 EXPRESSION IN A LARGE SERIES OF MESENCHYMAL TUMORS

    PubMed Central

    Demicco, Elizabeth G; Harms, Paul W; Patel, Rajiv M; Smith, Steven C; Ingram, Davis; Torres, Keila; Carskadon, Shannon L; Camelo-Piragua, Sandra; McHugh, Jonathan B; Siddiqui, Javed; Palanisamy, Nallasivam; Lucas, David R; Lazar, Alexander J; Wang, Wei-lien

    2015-01-01

    Objectives Expression of strong nuclear STAT6 is thought to be a specific marker for solitary fibrous tumors (SFT). Little is known about subtle expression patterns in other mesenchymal lesions. Methods We performed immunohistochemical studies against the C-terminus of STAT6 in tissue microarrays and whole sections, comprising 2366 mesenchymal lesions. Results Strong nuclear STAT6 was expressed in 285/2021 tumors, including 206/240 SFT, 49/408 well/dedifferentiated liposarcomas, 8/65 unclassified sarcomas, and 14/184 desmoids, among others. Expression in SFT was predominately limited to the nucleus. Other positive tumors typically expressed both nuclear and cytoplasmic STAT6. Complete absence of STAT6 was most common in pleomorphic liposarcoma and alveolar soft part sarcoma (60% and 72% cases negative, respectively). Conclusions Strong nuclear STAT6 is largely specific for SFT. Physiologic low-level cytoplasmic/nuclear expression is common in mesenchymal neoplasia, and is of uncertain significance. PMID:25873501

  5. Phoenix Telltale Movie with Clouds, Sol 103

    NASA Technical Reports Server (NTRS)

    2008-01-01

    NASA's Phoenix Mars Lander's telltale catches a breeze as clouds move over the landing site on Sol 103 (Sept. 7, 2008), the 103rd Martian day since landing.

    Phoenix's Surface Stereo Imager took this series of images during daily telltale monitoring around 3 p.m. local solar time and captured the clouds moving over the landing site.

    Phoenix can measure wind speed and direction by imaging the telltale, which is about about 10 centimeters (4 inches) tall. The telltale was built by the University of Aarhus, Denmark.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  6. Schiff base mediated sol-gel polymerization

    SciTech Connect

    Lindquist, D.A.; Harrison, C.M.; Williams, B.; Morris, R.D.

    1996-12-31

    Formation of a Schiff base imine by reacting a primary amine with either an aldehyde or ketone was initiated by an aluminum compound acting as a Lewis acid catalyst. The water byproduct of the reaction then was used as an in situ reagent for subsequent hydrolysis and sol-gel condensation of the aluminum species. These reactions yielded a gel network containing the entrained Schiff base. Two examples of this synthetic approach are described with two different aluminum catalyst/reagents: a diethylaluminum diethylphosphate ester [(CH{sub 3}CH{sub 2}){sub 2}Al-O-P(O)(OCH{sub 2}CH{sub 3}){sub 2}] and triethyl aluminum [Al(CH{sub 3}CH{sub 2}){sub 3}]. Anhydrous ammonia and acetone were used as the Schiff base precursors.

  7. Sol-gel processing of energetic materials

    SciTech Connect

    Tillotson, T.M.; Hrubesh, L.H.; Fox, G.L.; Simpson, R.L.; Lee, R.W.; Swansiger, R.W.; Simpson, L.R.

    1997-08-18

    As part of a new materials effort, we are exploring the use of sol- gel chemistry to manufacture energetic materials. Traditional manufacturing of energetic materials involves processing of granular solids. One application is the production of detonators where powders of energetic material and a binder are typically mixed and compacted at high pressure to make pellets. Performance properties are strongly dependent on particle size distribution, surface area of its constituents, homogeneity of the mix, and void volume. The goal is to produce detonators with fast energy release rate the are insensitive to unintended initiation. In this paper, we report results of our early work in this field of research, including the preparation of detonators from xerogel molding powders and aerogels, comparing the material properties with present state-of-the-art technology.

  8. Comment on ``Study of dielectric relaxations of anhydrous trehalose and maltose glasses'' [J. Chem. Phys. 134, 014508 (2011)

    NASA Astrophysics Data System (ADS)

    Kaminski, K.; Wlodarczyk, P.; Paluch, M.

    2011-10-01

    Very recently Kwon et al. [H.-J. Kwon, J.-A. Seo, H. K. Kim, and Y. H. Hwang, J. Chem. Phys. 134, 014508 (2011)] published an article on the study of dielectric relaxation in trehalose and maltose glasses. They carried out broadband dielectric measurements at very wide range of temperatures covering supercooled liquid as well as glassy state of both saccharides. It is worth to mention that authors have also applied a new method for obtaining anhydrous glasses of trehalose and maltose that enables avoiding their caramelization. Four relaxation processes were identified in dielectric spectra of both saccharides. The slower one was identified as structural relaxation process the next one, not observed by the others, was assigned as Johari-Goldstein (JG) β-relaxation, while the last two secondary modes were of the same nature as found by Kaminski et al. [K. Kaminski, E. Kaminska, P. Wlodarczyk, S. Pawlus, D. Kimla, A. Kasprzycka, M. Paluch, J. Ziolo, W. Szeja, and K. L. Ngai, J. Phys. Chem. B 112, 12816 (2008)]. In this comment we show that the authors mistakenly assigned the slowest relaxation process as structural mode of disaccharides. We have proven that this relaxation process is an effect of formation of thin layer of air or water between plate of capacitor and sample. The same effect can be observed if plates of capacitor are oxidized. Thus, we concluded that their slowest mode is connected to the dc conduction process while their β JG process is primary relaxation of trehalose and maltose.

  9. Martian Arctic Dust Devil, Phoenix Sol 104

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Surface Stereo Imager on NASA's Phoenix Mars Lander caught this dust devil in action west-southwest of the lander at 11:16 a.m. local Mars time on Sol 104, or the 104th Martian day of the mission, Sept. 9, 2008.

    Dust devils have not been detected in any Phoenix images from earlier in the mission, but at least six were observed in a dozen images taken on Sol 104.

    Dust devils are whirlwinds that often occur when the Sun heats the surface of Mars, or some areas on Earth. The warmed surface heats the layer of atmosphere closest to it, and the warm air rises in a whirling motion, stirring dust up from the surface like a miniature tornado.

    The dust devil visible in the center of this image just below the horizon is estimated to be about 400 meters (about 1,300 feet) from Phoenix, and 4 meters (13 feet) in diameter. It is much smaller than dust devils that have been observed by NASA's Mars Exploration Rover Spirit much closer to the equator. It is closer in size to dust devils seen from orbit in the Phoenix landing region, though still smaller than those.

    The image has been enhanced to make the dust devil easier to see.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  10. Opportunity's Heat Shield in Color, Sol 335

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This image from the panoramic camera on NASA's Mars Exploration Rover Opportunity features the remains of the heat shield that protected the rover from temperatures of up to 2,000 degrees Fahrenheit as it made its way through the martian atmosphere. This two-frame mosaic was taken on the rover's 335th martian day, or sol, (Jan. 2, 2004).

    The view is of the main heat shield debris seen from approximately 10 meters (about 33 feet) away from it. Many rover-team engineers were taken aback when they realized the heat shield had inverted, or turned itself inside out. The height of the pictured debris is about 1.3 meters (about 4.3 feet). The original diameter was 2.65 meters (8.7 feet), though it has obviously been deformed. The Sun reflecting off of the aluminum structure accounts for the vertical blurs in the picture.

    The fact that the heat shield is now inside out makes it more challenging to evaluate the state of the thermal protection system that is now on the inside. In coming sols, Opportunity will investigate the debris with its microscopic imager.

    Engineers who designed and built the heat shield are thrilled to see the hardware on the surface of Mars. This provides a unique opportunity to look at how the thermal protection system material survived the actual Mars entry. Team members hope this information will allow them to compare their predictions to what really happened.

    The image is an approximately true-color rendering generated using the panoramic camera's 600, 530 and 480 nanometer filters.

  11. StreamStats: A Water Resources Web Application

    USGS Publications Warehouse

    Ries, Kernell G.; Guthrie, John G.; Rea, Alan H.; Steeves, Peter A.; Stewart, David W.

    2008-01-01

    . Streamflow measurements are collected systematically over a period of years at partial-record stations to estimate peak-flow or low-flow statistics. Streamflow measurements usually are collected at miscellaneous-measurement stations for specific hydrologic studies with various objectives. StreamStats is a Web-based Geographic Information System (GIS) application (fig. 1) that was created by the USGS, in cooperation with Environmental Systems Research Institute, Inc. (ESRI)1, to provide users with access to an assortment of analytical tools that are useful for water-resources planning and management. StreamStats functionality is based on ESRI's ArcHydro Data Model and Tools, described on the Web at http://support.esri.com/index.cfm?fa=downloads.dataModels.filteredGateway&dmid=15. StreamStats allows users to easily obtain streamflow statistics, basin characteristics, and descriptive information for USGS data-collection stations and user-selected ungaged sites. It also allows users to identify stream reaches that are upstream and downstream from user-selected sites, and to identify and obtain information for locations along the streams where activities that may affect streamflow conditions are occurring. This functionality can be accessed through a map-based user interface that appears in the user's Web browser (fig. 1), or individual functions can be requested remotely as Web services by other Web or desktop computer applications. StreamStats can perform these analyses much faster than historically used manual techniques. StreamStats was designed so that each state would be implemented as a separate application, with a reliance on local partnerships to fund the individual applications, and a goal of eventual full national implementation. Idaho became the first state to implement StreamStats in 2003. By mid-2008, 14 states had applications available to the public, and 18 other states were in various stages of implementation.

  12. Early Activation of STAT3 Regulates Reactive Astrogliosis Induced by Diverse Forms of Neurotoxicity

    PubMed Central

    O'Callaghan, James P.; Kelly, Kimberly A.; VanGilder, Reyna L.; Sofroniew, Michael V.; Miller, Diane B.

    2014-01-01

    Astrogliosis, a cellular response characterized by astrocytic hypertrophy and accumulation of GFAP, is a hallmark of all types of central nervous system (CNS) injuries. Potential signaling mechanisms driving the conversion of astrocytes into “reactive” phenotypes differ with respect to the injury models employed and can be complicated by factors such as disruption of the blood-brain barrier (BBB). As denervation tools, neurotoxicants have the advantage of selective targeting of brain regions and cell types, often with sparing of the BBB. Previously, we found that neuroinflammation and activation of the JAK2-STAT3 pathway in astrocytes precedes up regulation of GFAP in the MPTP mouse model of dopaminergic neurotoxicity. Here we show that multiple mechanistically distinct mouse models of neurotoxicity (MPTP, AMP, METH, MDA, MDMA, KA, TMT) engender the same neuroinflammatory and STAT3 activation responses in specific regions of the brain targeted by each neurotoxicant. The STAT3 effects seen for TMT in the mouse could be generalized to the rat, demonstrating cross-species validity for STAT3 activation. Pharmacological antagonists of the neurotoxic effects blocked neuroinflammatory responses, pSTAT3tyr705 and GFAP induction, indicating that damage to neuronal targets instigated astrogliosis. Selective deletion of STAT3 from astrocytes in STAT3 conditional knockout mice markedly attenuated MPTP-induced astrogliosis. Monitoring STAT3 translocation in GFAP-positive cells indicated that effects of MPTP, METH and KA on pSTAT3tyr705 were localized to astrocytes. These findings strongly implicate the STAT3 pathway in astrocytes as a broadly triggered signaling pathway for astrogliosis. We also observed, however, that the acute neuroinflammatory response to the known inflammogen, LPS, can activate STAT3 in CNS tissue without inducing classical signs of astrogliosis. Thus, acute phase neuroinflammatory responses and neurotoxicity-induced astrogliosis both signal through

  13. Association of STAT3 with Cx26 and Cx43 in human uterine endometrioid adenocarcinoma

    PubMed Central

    SULKOWSKA, URSZULA; FEBP, ANDRZEJ WINCEWICZ; SULKOWSKI, STANISLAW

    2016-01-01

    Signal transducer and activator of transcription-3 (STAT3) drives endometrial carcinogenesis, while signaling via gap junctions gets weakened during cancer progression. Connexin 26 (Cx26), Cx43 and STAT3 were immunohistochemically evaluated in 78 endometrioid adenocarcinomas: Nuclear expression of STAT3 positively correlated with cytoplasmic immunoreactivity to Cx43 (P=0.004, r=0.318) and Cx26 (P=0.006, r=0.309). STAT3 correlated with Cx43 (P=0.022, r=0.411) and Cx26 (P=0.008 r=0.466) in G1 tumors. A statistically significant linkage remained in G2 cancers between STAT3 and Cx43 (P=0.061, r=0.262) and Cx26 (P=0.016, r=0.331); however, no correlations were observed in G3 tumors. STAT3 was significantly associated with Cx 43 (p=0.003, r=0.684) and Cx26 (p=0.049, r=0.500) in estrogen receptor (ER) negative adenocarcinomas. STAT3 did not correlate with Cx43 in ER positive adenocarcinomas; however, STAT3 expression remained correlated with Cx26 expression (P=0.035, r=0.268). In progesterone receptor negative tumors STAT3 was significantly associated with Cx43 (P=0.035, r=0.451) and Cx26 (P<0.0001, r=0.707). However, in PgR positive adenocarcinomas STAT3 correlated with Cx43 (P=0.03, r=0.290) but not with Cx26. Thus, it appears that hormone dependent acceleration of cancer growth breaks the association between STAT3 and Cx expression. These associations become weaker as the tumors dedifferentiate from G1 to G3 endometrioid adenocarcinomas. The present study provides evidence that the loss of correlation between STAT3 and selected Cx proteins occurs in tumors with more aggressive behavior. PMID:27313754

  14. Significance of Stat3 Signaling in Epithelial Cell Differentiation of Fetal Mouse Lungs

    PubMed Central

    Kameyama, Hiroki; Kudoh, Shinji; Hatakeyama, Jun; Matuo, Akira; Ito, Takaaki

    2017-01-01

    To study the significance of signal transducer and activator of transcription (Stat) 3 in lung epithelial development of fetal mice, we examined fetal mouse lungs, focusing on the expression of Clara cell secretory protein (CCSP), Forkhead box protein J1 (Foxj1), calcitonin gene-related peptide (CGRP), phosphorylated Stat3 (Tyr705), and hairy/enhancer of split (Hes) 1, and observed cultured fetal lungs upon treatment with IL-6, a Stat3 activator, or cucurbitacin I, a Stat3 inhibitor. Moreover, the interaction of Stat3 signaling and Hes1 was studied using Hes1 gene-deficient mice. Phosphorylated Stat3 was detected in fetal lungs and, immunohistochemically, phosphorylated Stat3 was found to be co-localized in developing Clara cells, but not in ciliated cells. In the organ culture studies, upon treatment with IL-6, quantitative RT-PCR revealed that CCSP mRNA increased with increasing Stat3 phosphorylation, while cucurbitacin I decreased Hes1, CCSP, Foxj1 and CGRP mRNAs with decreasing Stat3 phosphorylation. In the lungs of Hes1 gene-deficient mice, Stat3 phosphorylation was not markedly different from wild-type mice, the expression of CCSP and CGRP was enhanced, and the treatment of IL-6 or cucurbitacin I induced similar effects on mouse lung epithelial differentiation regardless of Hes1 expression status. Stat3 signaling acts in fetal mouse lung development, and seems to regulate Clara cell differentiation positively. Hes1 could regulate Clara cell differentiation in a manner independent from Stat3 signaling. PMID:28386145

  15. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent.

    PubMed

    Chen, Jane Q; Mori, Hidetoshi; Cardiff, Robert D; Trott, Josephine F; Hovey, Russell C; Hubbard, Neil E; Engelberg, Jesse A; Tepper, Clifford G; Willis, Brandon J; Khan, Imran H; Ravindran, Resmi K; Chan, Szeman R; Schreiber, Robert D; Borowsky, Alexander D

    2015-01-01

    Female 129:Stat1-null mice (129S6/SvEvTac-Stat1(tm1Rds) homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment.

  16. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent

    PubMed Central

    Cardiff, Robert D.; Trott, Josephine F.; Hovey, Russell C.; Hubbard, Neil E.; Engelberg, Jesse A.; Tepper, Clifford G.; Willis, Brandon J.; Khan, Imran H.; Ravindran, Resmi K.; Chan, Szeman R.; Schreiber, Robert D.; Borowsky, Alexander D.

    2015-01-01

    Female 129:Stat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment. PMID:26075897

  17. Regulation of Natural Killer Cell Function by STAT3

    PubMed Central

    Cacalano, Nicholas A.

    2016-01-01

    Natural killer (NK) cells, key members of a distinct hematopoietic lineage, innate lymphoid cells, are not only critical effectors that mediate cytotoxicity toward tumor and virally infected cells but also regulate inflammation, antigen presentation, and the adaptive immune response. It has been shown that NK cells can regulate the development and activation of many other components of the immune response, such as dendritic cells, which in turn, modulate the function of NK cells in multiple synergistic feed back loops driven by cell–cell contact, and the secretion of cytokines and chemokines that control effector function and migration of cells to sites of immune activation. The signal transducer and activator of transcription (STAT)-3 is involved in driving almost all of the pathways that control NK cytolytic activity as well as the reciprocal regulatory interactions between NK cells and other components of the immune system. In the context of tumor immunology, NK cells are a first line of defense that eliminates pre-cancerous and transformed cells early in the process of carcinogenesis, through a mechanism of “immune surveillance.” Even after tumors become established, NK cells are critical components of anticancer immunity: dysfunctional NK cells are often found in the peripheral blood of cancer patients, and the lack of NK cells in the tumor microenvironment often correlates to poor prognosis. The pathways and soluble factors activated in tumor-associated NK cells, cancer cells, and regulatory myeloid cells, which determine the outcome of cancer immunity, are all critically regulated by STAT3. Using the tumor microenvironment as a paradigm, we present here an overview of the research that has revealed fundamental mechanisms through which STAT3 regulates all aspects of NK cell biology, including NK development, activation, target cell killing, and fine tuning of the innate and adaptive immune responses. PMID:27148255

  18. Modified silica sol coatings for surface enhancement of leather.

    PubMed

    Mahltig, Boris; Vossebein, Lutz; Ehrmann, Andrea; Cheval, Nicolas; Fahmi, Amir

    2012-06-01

    The presented study reports on differently modified silica sols for coating applications on leather. Silica sols are prepared by acidic hydrolysis of tetraethoxysilane and modified by silane compounds with fluorinated and non-fluorinated alkylgroups. In contrast to many earlier investigations regarding sol-gel applications on leather, no acrylic resin is used together with the silica sols when applying on leather. The modified silica particles are supposed to aggregate after application, forming thus a modified silica coating on the leather substrate. Scanning electron microscopy investigation shows that the applied silica coatings do not fill up or close the pores of the leather substrate. However, even if the pores of the leather are not sealed by this sol-gel coating, an improvement of the water repellent and oil repellent properties of the leather substrates are observed. These improved properties of leather by application of modified silica sols can provide the opportunity to develop sol-gel products for leather materials present in daily life.

  19. STAT1, STAT3 and p38MAPK are involved in the apoptotic effect induced by a chimeric cyclic interferon-{alpha}2b peptide

    SciTech Connect

    Blank, Viviana C.; Pena, Clara; Roguin, Leonor P.

    2010-02-15

    In the search of mimetic peptides of the interferon-{alpha}2b molecule (IFN-{alpha}2b), we have previously designed and synthesized a chimeric cyclic peptide of the IFN-{alpha}2b that inhibits WISH cell proliferation by inducing an apoptotic response. Here, we first studied the ability of this peptide to activate intracellular signaling pathways and then evaluated the participation of some signals in the induction of apoptosis. Stimulation of WISH cells with the cyclic peptide showed tyrosine phosphorylation of Jak1 and Tyk2 kinases, tyrosine and serine phosphorylation of STAT1 and STAT3 transcription factors and activation of p38 MAPK pathway, although phosphorylation levels or kinetics were in some conditions different to those obtained under IFN-{alpha}2b stimulus. JNK and p44/42 pathways were not activated by the peptide in WISH cells. We also showed that STAT1 and STAT3 downregulation by RNA interference decreased the antiproliferative activity and the amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.

  20. Jak/STAT Inhibition to Prevent Post-Traumatic Epileptogenesis

    DTIC Science & Technology

    2012-07-01

    Supporting Data: Figure 9 and 10 1i. Assess mossy fiber sprouting, cell loss and glial proliferation 10 weeks post injury using Timm and Nissl ...using Timm and Nissl staining (40 mice [subset of mice used in Task 2h]; months 24-26). 2j. Assess pSTAT3, ICER and Gabra1 protein levels 10 weeks...phosphate-buffered aline; 20m coronal brain sections were cut on a cryostat and ollected at 400m intervals. Timm’s and Nissl staining was per- ormed as

  1. A Chemical Biology Approach to Developing STAT Inhibitors: Molecular Strategies for Accelerating Clinical Translation

    PubMed Central

    Nelson, Erik A.; Sharma, Sreenath V.; Settleman, Jeffrey; Frank, David A.

    2011-01-01

    STAT transcription factors transduce signals from the cell surface to the nucleus, where they regulate the expression of genes that control proliferation, survival, self-renewal, and other critical cellular functions. Under normal physiological conditions, the activation of STATs is tightly regulated. In cancer, by contrast, STAT proteins, particularly STAT3 and STAT5, become activated constitutively, thereby driving the malignant phenotype of cancer cells. Since these proteins are largely dispensable in the function of normal adult cells, STATs represent a potentially important target for cancer therapy. Although transcription factors have traditionally been viewed as suboptimal targets for pharmacological inhibition, chemical biology approaches have been particularly fruitful in identifying compounds that can modulate this pathway through a variety of mechanisms. STAT inhibitors have notable anti-cancer effects in many tumor systems, show synergy with other therapeutic modalities, and have the potential to eradicate tumor stem cells. Furthermore, STAT inhibitors identified through the screening of chemical libraries can then be employed in large scale analyses such as gene expression profiling, RNA interference screens, or large-scale tumor cell line profiling. Data derived from these studies can then provide key insights into mechanisms of STAT signal transduction, as well as inform the rational design of targeted therapeutic strategies for cancer patients. PMID:21680956

  2. STAT3 Expression, Molecular Features, Inflammation Patterns and Prognosis in a Database of 724 Colorectal Cancers

    PubMed Central

    Morikawa, Teppei; Baba, Yoshifumi; Yamauchi, Mai; Kuchiba, Aya; Nosho, Katsuhiko; Shima, Kaori; Tanaka, Noriko; Huttenhower, Curtis; Frank, David A.; Fuchs, Charles S.; Ogino, Shuji

    2010-01-01

    Purpose STAT3 (signal transducer and activator of transcription 3) is a transcription factor that is constitutively activated in some cancers. STAT3 appears to play crucial roles in cell proliferation and survival, angiogenesis, tumor-promoting inflammation and suppression of anti-tumor host immune response in the tumor microenvironment. Although the STAT3 signaling pathway is a potential drug target, clinical, pathologic, molecular or prognostic features of STAT3-activated colorectal cancer remain uncertain. Experimental Design Utilizing a database of 724 colon and rectal cancer cases, we evaluated phosphorylated STAT3 (p-STAT3) expression by immunohistochemistry. Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for clinical, pathologic and molecular features, including microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), LINE-1 methylation, 18q loss of heterozygosity, TP53 (p53), CTNNB1 (β-catenin), JC virus T-antigen, and KRAS, BRAF, and PIK3CA mutations. Results Among the 724 tumors, 131 (18%) showed high-level p-STAT3 expression (p-STAT3-high), 244 (34%) showed low-level expression (p-STAT3-low), and the remaining 349 (48%) were negative for p-STAT3. p-STAT3 overexpression was associated with significantly higher colorectal cancer-specific mortality [log-rank p=0.0020; univariate HR (p-STAT3-high vs. p-STAT3-negative) 1.85, 95% confidence interval (CI) 1.30–2.63, Ptrend =0.0005; multivariate HR, 1.61, 95% CI 1.11–2.34, Ptrend =0.015). p-STAT3 expression was positively associated with peritumoral lymphocytic reaction (multivariate odds ratio 3.23; 95% CI, 1.89–5.53; p<0.0001). p-STAT3 expression was not associated with MSI, CIMP, or LINE-1 hypomethylation. Conclusions STAT3 activation in colorectal cancer is associated with adverse clinical outcome, supporting its potential roles as a prognostic biomarker and a chemoprevention and/or therapeutic target. PMID:21310826

  3. The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors

    PubMed Central

    Nelson, Erik A.; Walker, Sarah R.; Weisberg, Ellen; Bar-Natan, Michal; Barrett, Rosemary; Gashin, Laurie B.; Terrell, Shariya; Klitgaard, Josephine L.; Santo, Loredana; Addorio, Martha R.; Ebert, Benjamin L.; Griffin, James D.

    2011-01-01

    The transcription factor STAT5 is an essential mediator of the pathogenesis of chronic myelogenous leukemia (CML). In CML, the BCR/ABL fusion kinase causes the constitutive activation of STAT5, thereby driving the expression of genes promoting survival. BCR/ABL kinase inhibitors have become the mainstay of therapy for CML, although CML cells can develop resistance through mutations in BCR/ABL. To overcome this problem, we used a cell-based screen to identify drugs that inhibit STAT-dependent gene expression. Using this approach, we identified the psychotropic drug pimozide as a STAT5 inhibitor. Pimozide decreases STAT5 tyrosine phosphorylation, although it does not inhibit BCR/ABL or other tyrosine kinases. Furthermore, pimozide decreases the expression of STAT5 target genes and induces cell cycle arrest and apoptosis in CML cell lines. Pimozide also selectively inhibits colony formation of CD34+ bone marrow cells from CML patients. Importantly, pimozide induces similar effects in the presence of the T315I BCR/ABL mutation that renders the kinase resistant to presently available inhibitors. Simultaneously inhibiting STAT5 with pimozide and the kinase inhibitors imatinib or nilotinib shows enhanced effects in inhibiting STAT5 phosphorylation and in inducing apoptosis. Thus, targeting STAT5 may be an effective strategy for the treatment of CML and other myeloproliferative diseases. PMID:21233313

  4. Disruption of STAT3 signalling promotes KRAS-induced lung tumorigenesis

    PubMed Central

    Grabner, Beatrice; Schramek, Daniel; Mueller, Kristina M.; Moll, Herwig P.; Svinka, Jasmin; Hoffmann, Thomas; Bauer, Eva; Blaas, Leander; Hruschka, Natascha; Zboray, Katalin; Stiedl, Patricia; Nivarthi, Harini; Bogner, Edith; Gruber, Wolfgang; Mohr, Thomas; Zwick, Ralf Harun; Kenner, Lukas; Poli, Valeria; Aberger, Fritz; Stoiber, Dagmar; Egger, Gerda; Esterbauer, Harald; Zuber, Johannes; Moriggl, Richard; Eferl, Robert; Győrffy, Balázs; Penninger, Josef M.; Popper, Helmut; Casanova, Emilio

    2015-01-01

    STAT3 is considered to play an oncogenic role in several malignancies including lung cancer; consequently, targeting STAT3 is currently proposed as therapeutic intervention. Here we demonstrate that STAT3 plays an unexpected tumour-suppressive role in KRAS mutant lung adenocarcinoma (AC). Indeed, lung tissue-specific inactivation of Stat3 in mice results in increased KrasG12D-driven AC initiation and malignant progression leading to markedly reduced survival. Knockdown of STAT3 in xenografted human AC cells increases tumour growth. Clinically, low STAT3 expression levels correlate with poor survival and advanced malignancy in human lung AC patients with smoking history, which are prone to KRAS mutations. Consistently, KRAS mutant lung tumours exhibit reduced STAT3 levels. Mechanistically, we demonstrate that STAT3 controls NF-κB-induced IL-8 expression by sequestering NF-κB within the cytoplasm, thereby inhibiting IL-8-mediated myeloid tumour infiltration and tumour vascularization and hence tumour progression. These results elucidate a novel STAT3–NF-κB–IL-8 axis in KRAS mutant AC with therapeutic and prognostic relevance. PMID:25734337

  5. STAT3 overexpression promotes metastasis in intrahepatic cholangiocarcinoma and correlates negatively with surgical outcome.

    PubMed

    Yang, Xin-Wei; Li, Liang; Hou, Guo-Jun; Yan, Xin-Zhou; Xu, Qin-Guo; Chen, Lei; Zhang, Bao-Hua; Shen, Feng

    2017-01-31

    Signal transducer and activator of transcription 3 (STAT3) promotes tumor progression in many types of cancer. In this study, we analyzed the prognostic value of this marker in human intrahepatic cholangiocarcinoma (ICC). Using real-time PCR, western blot and immunohistochemistry assays, we found that STAT3 is overexpressed in ICC patients. STAT3 expression correlated with several clinicopathological features, including tumor size, pathological satellite, vascular invasion, undifferentiated-type histology, lymph node metastasis and TNM stage in two independent cohorts of ICC patients. Patients with high STAT3 levels had a poor prognosis in terms of overall survival (OS) and disease-free survival (DFS). Multivariate survival analysis indicated that STAT3 is an independent prognostic factor for OS and DFS. Furthermore, we observed that STAT3 overexpression promotes the invasion, metastasis and proliferation of ICC cells in vitro and in vivo, and also promotes STAT3 phosphorylation. These findings suggest that STAT3 expression correlated negatively with surgical outcome and inhibition of STAT3 expression may constitute a novel target for the treatment of ICC patients.

  6. High glucose enhances progression of cholangiocarcinoma cells via STAT3 activation.

    PubMed

    Saengboonmee, Charupong; Seubwai, Wunchana; Pairojkul, Chawalit; Wongkham, Sopit

    2016-01-08

    Epidemiological studies have indicated diabetes mellitus (DM) as a risk of cholangiocarcinoma (CCA), however, the effects and mechanisms of high glucose on progression of CCA remain unclear. This study reports for the first time of the enhancing effects of high glucose on aggressive phenotypes of CCA cells via STAT3 activation. CCA cells cultured in high glucose media exerted significantly higher rates of cell proliferation, adhesion, migration and invasion than those cultured in normal glucose. The phosphokinase array revealed STAT3 as the dominant signal activated in response to high glucose. Increased nuclear STAT3, p-STAT3 and its downstream target proteins, cyclin D1, vimentin and MMP2, were shown to be underling mechanisms of high glucose stimulation. The link of high glucose and STAT3 activation was confirmed in tumor tissues from CCA patients with DM that exhibited higher STAT3 activation than those without DM. Moreover, the levels of STAT3 activation were correlated with the levels of blood glucose. Finally, decreasing the level of glucose or using a STAT3 inhibitor could reduce the effects of high glucose. These findings suggest that controlling blood glucose or using a STAT3 inhibitor as an alternative approach may improve the therapeutic outcome of CCA patients with DM.

  7. Paeoniflorin inhibits human glioma cells via STAT3 degradation by the ubiquitin–proteasome pathway

    PubMed Central

    Nie, Xiao-hu; Ou-yang, Jia; Xing, Ying; Li, Dan-yan; Dong, Xing-yu; Liu, Ru-en; Xu, Ru-xiang

    2015-01-01

    We investigated the underlying mechanism for the potent proapoptotic effect of paeoniflorin (PF) on human glioma cells in vitro, focusing on signal transducer and activator of transcription 3 (STAT3) signaling. Significant time- and dose-dependent apoptosis and inhibition of proliferation were observed in PF-treated U87 and U251 glioma cells. Expression of STAT3, its active form phosphorylated STAT3 (p-STAT3), and several downstream molecules, including HIAP, Bcl-2, cyclin D1, and Survivin, were significantly downregulated upon PF treatment. Overexpression of STAT3 induced resistance to PF, suggesting that STAT3 was a critical target of PF. Interestingly, rapid downregulation of STAT3 was consistent with its accelerated degradation, but not with its dephosphorylation or transcriptional modulation. Using specific inhibitors, we demonstrated that the prodegradation effect of PF on STAT3 was mainly through the ubiquitin–proteasome pathway rather than via lysosomal degradation. These findings indicated that PF-induced growth suppression and apoptosis in human glioma cells through the proteasome-dependent degradation of STAT3. PMID:26508835

  8. Involvement of Stat3 in mouse brain development and sexual dimorphism: a proteomics approach.

    PubMed

    Di Domenico, Fabio; Casalena, Gabriella; Sultana, Rukhsana; Cai, Jian; Pierce, William M; Perluigi, Marzia; Cini, Chiara; Baracca, Alessandra; Solaini, Giancarlo; Lenaz, Giorgio; Jia, Jia; Dziennis, Suzan; Murphy, Stephanie J; Alkayed, Nabil J; Butterfield, D Allan

    2010-11-29

    Although the role of STAT3 in cell physiology and tissue development has been largely investigated, its involvement in the development and maintenance of nervous tissue and in the mechanisms of neuroprotection is not yet known. The potentially wide range of STAT3 activities raises the question of tissue- and gender-specificity as putative mechanisms of regulation. To explore the function of STAT3 in the brain and the hypothesis of a gender-linked modulation of STAT3, we analyzed a neuron-specific STAT3 knockout mouse model investigating the influence of STAT3 activity in brain protein expression pattern in both males and females in the absence of neurological insult. We performed a proteomic study aimed to reveal the molecular pathways directly or indirectly controlled by STAT3 underscoring its role in brain development and maintenance. We identified several proteins, belonging to different neuronal pathways such as energy metabolism or synaptic transmission, controlled by STAT3 that confirm its crucial role in brain development and maintenance. Moreover, we investigated the different processes that could contribute to the sexual dimorphic behavior observed in the incidence of neurological and mental disease. Interestingly both STAT3 KO and gender factors influence the expression of several mitochondrial proteins conferring to mitochondrial activity high importance in the regulation of brain physiology and conceivable relevance as therapeutic target.

  9. Revealing the cellular localization of STAT1 during the cell cycle by super-resolution imaging

    NASA Astrophysics Data System (ADS)

    Gao, Jing; Wang, Feng; Liu, Yanhou; Cai, Mingjun; Xu, Haijiao; Jiang, Junguang; Wang, Hongda

    2015-03-01

    Signal transducers and activators of transcription (STATs) can transduce cytokine signals and regulate gene expression. The cellular localization and nuclear trafficking of STAT1, a representative of the STAT family with multiple transcriptional functions, is tightly related with transcription process, which usually happens in the interphase of the cell cycle. However, these priority questions regarding STAT1 distribution and localization at the different cell-cycle stages remain unclear. By using direct stochastic optical reconstruction microscopy (dSTORM), we found that the nuclear expression level of STAT1 increased gradually as the cell cycle carried out, especially after EGF stimulation. Furthermore, STAT1 formed clusters in the whole cell during the cell cycle, with the size and the number of clusters also increasing significantly from G1 to G2 phase, suggesting that transcription and other cell-cycle related activities can promote STAT1 to form more and larger clusters for fast response to signals. Our work reveals that the cellular localization and clustering distribution of STAT1 are associated with the cell cycle, and further provides an insight into the mechanism of cell-cycle regulated STAT1 signal transduction.

  10. Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations.

    PubMed

    Milner, Joshua D; Vogel, Tiphanie P; Forbes, Lisa; Ma, Chi A; Stray-Pedersen, Asbjørg; Niemela, Julie E; Lyons, Jonathan J; Engelhardt, Karin R; Zhang, Yu; Topcagic, Nermina; Roberson, Elisha D O; Matthews, Helen; Verbsky, James W; Dasu, Trivikram; Vargas-Hernandez, Alexander; Varghese, Nidhy; McClain, Kenneth L; Karam, Lina B; Nahmod, Karen; Makedonas, George; Mace, Emily M; Sorte, Hanne S; Perminow, Gøri; Rao, V Koneti; O'Connell, Michael P; Price, Susan; Su, Helen C; Butrick, Morgan; McElwee, Joshua; Hughes, Jason D; Willet, Joseph; Swan, David; Xu, Yaobo; Santibanez-Koref, Mauro; Slowik, Voytek; Dinwiddie, Darrell L; Ciaccio, Christina E; Saunders, Carol J; Septer, Seth; Kingsmore, Stephen F; White, Andrew J; Cant, Andrew J; Hambleton, Sophie; Cooper, Megan A

    2015-01-22

    Germline loss-of-function mutations in the transcription factor signal transducer and activator of transcription 3 (STAT3) cause immunodeficiency, whereas somatic gain-of-function mutations in STAT3 are associated with large granular lymphocytic leukemic, myelodysplastic syndrome, and aplastic anemia. Recently, germline mutations in STAT3 have also been associated with autoimmune disease. Here, we report on 13 individuals from 10 families with lymphoproliferation and early-onset solid-organ autoimmunity associated with 9 different germline heterozygous mutations in STAT3. Patients exhibited a variety of clinical features, with most having lymphadenopathy, autoimmune cytopenias, multiorgan autoimmunity (lung, gastrointestinal, hepatic, and/or endocrine dysfunction), infections, and short stature. Functional analyses demonstrate that these mutations confer a gain-of-function in STAT3 leading to secondary defects in STAT5 and STAT1 phosphorylation and the regulatory T-cell compartment. Treatment targeting a cytokine pathway that signals through STAT3 led to clinical improvement in 1 patient, suggesting a potential therapeutic option for such patients. These results suggest that there is a broad range of autoimmunity caused by germline STAT3 gain-of-function mutations, and that hematologic autoimmunity is a major component of this newly described disorder. Some patients for this study were enrolled in a trial registered at www.clinicaltrials.gov as #NCT00001350.

  11. Epstein-Barr virus-derived EBNA2 regulates STAT3 activation

    SciTech Connect

    Muromoto, Ryuta; Ikeda, Osamu; Okabe, Kanako; Togi, Sumihito; Kamitani, Shinya; Fujimuro, Masahiro; Harada, Shizuko; Oritani, Kenji; Matsuda, Tadashi

    2009-01-16

    The Epstein-Barr virus (EBV)-encoded latency protein EBNA2 is a nuclear transcriptional activator that is essential for EBV-induced cellular transformation. Here, we show that EBNA2 interacts with STAT3, a signal transducer for an interleukin-6 family cytokine, and enhances the transcriptional activity of STAT3 by influencing its DNA-binding activity. Furthermore, EBNA2 cooperatively acts on STAT3 activation with LMP1. These data demonstrate that EBNA2 acts as a transcriptional coactivator of STAT3.

  12. Nuclear protein I{kappa}B-{zeta} inhibits the activity of STAT3

    SciTech Connect

    Wu, Zhihao; Zhang, Xiaoai; Yang, Juntao; Wu, Guangzhou; Zhang, Ying; Yuan, Yanzhi; Jin, Chaozhi; Chang, Zhijie; Wang, Jian; Yang, Xiaoming; He, Fuchu

    2009-09-18

    STAT3 (Signal transducer and activator of transcription 3) is a key transcription factor of the JAK-STAT (Janus kinase/signal transducer and activator of transcription) pathway that regulates cell proliferation and apoptosis. Activation of STAT3 is under tight regulation, and yet the different signaling pathways and the mechanisms that regulate its activity remain to be elucidated. Using a yeast two-hybrid screening, we have identified a nuclear protein I{kappa}B-{zeta} that interacts in a novel way with STAT3. This physical interaction was further confirmed by co-immunoprecipitation assays. The interaction regions were mapped to the coiled-coil domain of STAT3 and the C-terminal of I{kappa}B-{zeta}. Overexpression of I{kappa}B-{zeta} inhibited the transcriptional activity of STAT3. It also suppressed cell growth and induced cell apoptosis in SRC-simulated cells, which is partially mediated by down-regulation of expression of a known STAT3 target gene, MCL1. Our results suggest that I{kappa}B-{zeta} is a negative regulator of STAT3, and demonstrate a novel mechanism in which a component of the NF-{kappa}B signaling pathway inhibits the activation of STAT3.

  13. The role of STATs in transcriptional control and their impact on cellular function.

    PubMed

    Bromberg, J; Darnell, J E

    2000-05-15

    The STAT proteins (Signal Transducers and Activators of Transcription), were identified in the last decade as transcription factors which were critical in mediating virtually all cytokine driven signaling. These proteins are latent in the cytoplasm and become activated through tyrosine phosphorylation which typically occurs through cytokine receptor associated kinases (JAKs) or growth factor receptor tyrosine kinases. Recently a number of non-receptor tyrosine kinases (for example src and abl) have been found to cause STAT phosphorylation. Phosphorylated STATs form homo- or hetero-dimers, enter the nucleus and working coordinately with other transcriptional co-activators or transcription factors lead to increased transcriptional initiation. In normal cells and in animals, ligand dependent activation of the STATs is a transient process, lasting for several minutes to several hours. In contrast, in many cancerous cell lines and tumors, where growth factor dysregulation is frequently at the heart of cellular transformation, the STAT proteins (in particular Stats 1, 3 and 5) are persistently tyrosine phosphorylated or activated. The importance of STAT activation to growth control in experiments using anti-sense molecules or dominant negative STAT protein encoding constructs performed in cell lines or studies in animals lacking specific STATs strongly indicate that STATs play an important role in controlling cell cycle progression and apoptosis. Stat1 plays an important role in growth arrest, in promoting apoptosis and is implicated as a tumor suppressor; while Stats 3 and 5 are involved in promoting cell cycle progression and cellular transformation and preventing apoptosis. Many questions remain including: (1) a better understanding of how the STAT proteins through association with other factors increase transcription initiation; (2) a more complete definition of the sets of genes which are activated by different STATs and (3) how these sets of activated genes differ

  14. Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia.

    PubMed

    Schaefer, F; Chen, Y; Tsao, T; Nouri, P; Rabkin, R

    2001-08-01

    Chronic renal failure (CRF) is associated with resistance to the growth-promoting and anabolic actions of growth hormone (GH). In rats with CRF induced by partial renal ablation, 7 days of GH treatment had a diminished effect on weight gain and hepatic IGF-1 and IGFBP-1 mRNA levels, compared with sham-operated pair-fed controls. To assess whether GH resistance might be due to altered signal transduction, activation of the JAK-STAT pathway was studied 10 or 15 minutes after intravenous injection of 5 mg/kg GH or vehicle. Hepatic GH receptor (GHR) mRNA levels were significantly decreased in CRF, but GHR protein abundance and GH binding to microsomal and plasma membranes was unaltered. JAK2, STAT1, STAT3, and STAT5 protein abundance was also unchanged. However, GH-induced tyrosine phosphorylation of JAK2, STAT5, and STAT3 was 75% lower in the CRF animals. Phosphorylated STAT5 and STAT3 were also diminished in nuclear extracts. The expression of the suppressor of cytokine signaling-2 (SOCS-2) was increased twofold in GH-treated CRF animals, and SOCS-3 mRNA levels were elevated by 60% in CRF, independent of GH treatment. In conclusion, CRF causes a postreceptor defect in GH signal transduction characterized by impaired phosphorylation and nuclear translocation of GH-activated STAT proteins, which is possibly mediated, at least in part, by overexpression of SOCS proteins.

  15. T-cell growth transformation by herpesvirus saimiri is independent of STAT3 activation.

    PubMed

    Heck, Elke; Lengenfelder, Doris; Schmidt, Monika; Müller-Fleckenstein, Ingrid; Fleckenstein, Bernhard; Biesinger, Brigitte; Ensser, Armin

    2005-05-01

    Herpesvirus saimiri (saimirine herpesvirus 2) (HVS), a T-lymphotropic tumor virus, induces lymphoproliferative disease in several species of New World primates. In addition, strains of HVS subgroup C are able to transform T cells of Old World primates, including humans, to permanently growing T-cell lines. In concert with the Stp oncoprotein, the tyrosine kinase-interacting protein (Tip) of HVS C488 is required for T-cell transformation in vitro and lymphoma induction in vivo. Tip was previously shown to interact with the protein tyrosine kinase Lck. Constitutive activation of signal transducers and activators of transcription (STATs) has been associated with oncogenesis and has also been detected in HVS-transformed T-cell lines. Furthermore, Tip contains a putative consensus YXPQ binding motif for the SH2 (src homology 2) domains of STAT1 and STAT3. Tip tyrosine phosphorylation at this site was required for binding of STATs and induction of STAT-dependent transcription. Here we sought to address the relevance of STAT activation for transformation of human T cells by introducing a tyrosine-to-phenylalanine mutation in the YXPQ motif of Tip of HVS C488. Unexpectedly, the recombinant virus was still able to transform human T lymphocytes, but it had lost its capability to activate STAT3 as well as STAT1. This demonstrates that growth transformation by HVS is independent of STAT3 activation.

  16. Stat3 induces oncogenic Skp2 expression in human cervical carcinoma cells

    SciTech Connect

    Huang, Hanhui; Zhao, Wenrong; Yang, Dan

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Upregulation of Skp2 by IL-6 or Stat3 activation. Black-Right-Pointing-Pointer Stat3 activates Skp2 expression through bound to its promoter region. Black-Right-Pointing-Pointer Stat3 activates Skp2 expression through recruitment of P300. Black-Right-Pointing-Pointer Stat3 activation decreases the P27 stability. -- Abstract: Dysregulated Skp2 function promotes cell proliferation, which is consistent with observations of Skp2 over-expression in many types of human cancers, including cervical carcinoma (CC). However, the molecular mechanisms underlying elevated Skp2 expression have not been fully explored. Interleukin-6 (IL-6) induced Stat3 activation is viewed as crucial for multiple tumor growth and metastasis. Here, we demonstrate that Skp2 is a direct transcriptional target of Stat3 in the human cervical carcinoma cells. Our data show that IL-6 administration or transfection of a constitutively activated Stat3 in HeLa cells activates Skp2 mRNA transcription. Using luciferase reporter and ChIP assays, we show that Stat3 binds to the promoter region of Skp2 and promotes its activity through recruiting P300. As a result of the increase of Skp2 expression, endogenous p27 protein levels are markedly decreased. Thus, our results suggest a previously unknown Stat3-Skp2 molecular network controlling cervical carcinoma development.

  17. Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer

    PubMed Central

    Peyser, Noah D.; Pendleton, Kelsey; Gooding, William E.; Lui, Vivian W. Y.; Johnson, Daniel E.; Grandis, Jennifer R.

    2016-01-01

    Background Hyperactivation of STAT3 via constitutive phosphorylation of tyrosine 705 (Y705) is common in most human cancers, including head and neck squamous carcinoma (HNSCC). STAT3 is rarely mutated in cancer and the (epi)genetic alterations that lead to STAT3 activation are incompletely understood. Here we used an unbiased approach to identify genomic and epigenomic changes associated with pSTAT3(Y705) expression using data generated by The Cancer Genome Atlas (TCGA). Methods and Findings Mutation, mRNA expression, promoter methylation, and copy number alteration data were extracted from TCGA and examined in the context of pSTAT3(Y705) protein expression. mRNA expression levels of 1279 genes were found to be associated with pSTAT3(705) expression. Association of pSTAT3(Y705) expression with caspase-8 mRNA expression was validated by immunoblot analysis in HNSCC cells. Mutation, promoter hypermethylation, and copy number alteration of any gene were not significantly associated with increased pSTAT3(Y705) protein expression. Conclusions These cumulative results suggest that unbiased approaches may be useful in identifying the molecular underpinnings of oncogenic signaling, including STAT3 activation, in HNSCC. Larger datasets will likely be necessary to elucidate signaling consequences of infrequent alterations. PMID:27855189

  18. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model.

    PubMed

    Sano, Shigetoshi; Chan, Keith Syson; Carbajal, Steve; Clifford, John; Peavey, Mary; Kiguchi, Kaoru; Itami, Satoshi; Nickoloff, Brian J; DiGiovanni, John

    2005-01-01

    Here we report that epidermal keratinocytes in psoriatic lesions are characterized by activated Stat3. Transgenic mice with keratinocytes expressing a constitutively active Stat3 (K5.Stat3C mice) develop a skin phenotype either spontaneously, or in response to wounding, that closely resembles psoriasis. Keratinocytes from K5.Stat3C mice show upregulation of several molecules linked to the pathogenesis of psoriasis. In addition, the development of psoriatic lesions in K5.Stat3C mice requires cooperation between Stat3 activation in keratinocytes and activated T cells. Finally, abrogation of Stat3 function by a decoy oligonucleotide inhibits the onset and reverses established psoriatic lesions in K5.Stat3C mice. Thus, targeting Stat3 may be potentially therapeutic in the treatment of psoriasis.

  19. NAB2-STAT6 gene fusion and STAT6 immunoexpression in extrathoracic solitary fibrous tumors: the association between fusion variants and locations.

    PubMed

    Chuang, I-Chieh; Liao, Kuan-Cho; Huang, Hsuan-Ying; Kao, Yu-Chien; Li, Chien-Feng; Huang, Shih-Chiang; Tsai, Jen-Wei; Chen, Ko-Chin; Lan, Jui; Lin, Po-Chun

    2016-05-01

    Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm harboring NAB2-STAT6 fusion, which drives STAT6 nuclear relocation. For extrathoracic SFTs, the clinical relevance of this molecular hallmark remains obscure. We assessed STAT6 immunoexpression for 61 extrathoracic SFTs exclusive of the meninges and head and neck, and 25 had analyzable RNAs to distinguish fusion variants by RT-PCR. The immunohistochemical and molecular findings were correlated with clincopathological features and disease-free survival (DFS). Twenty-eight males and 33 females had SFTs in the body cavities (n = 31), extremities (n = 17), and trunk (n = 13), categorized into 53 non-malignant and 8 malignant tumors. The vast majority (n = 57, 93%) exhibited distinctive STAT6 nuclear expression, including malignant ones. The common fusion variants were NAB2ex6-STAT6ex16/17 in 13 SFTs and NAB2ex4-STAT6ex2 in 8, while miscellaneous variants were detected only in 4 SFTs in the limbs and trunk but not in any body cavity-based cases (P = 0.026). The worse DFS was univariately associated with malignant histology (P = 0.04) but unrelated to tumor size, location, or fusion variant. Conclusively, extrathoracic SFTs mostly harbor NAB2ex6-STAT6ex16/17, followed by NAB2ex4-STAT6ex2. Miscellaneous variants are significantly rare in SFTs within the body cavities. The clinical aggressiveness of extrathoraic SFTs is associated with malignant histology but unrelated to the NAB2-STAT6 fusion variants.

  20. Signal transducer and activator of transcription 3 (STAT3) homologue in turbot (Scophthalmus maximus): molecular characterization and expression analysis.

    PubMed

    Wang, Na; Yang, Chang-Geng; Sun, Zhong-Zhi; Wang, Xian-Li; Chen, Song-Lin

    2011-01-01

    Signal transducer and activator of transcription 3 (STAT3) acts as an important mediator in multiple biological processes induced by different cytokines. So far, little information is available in fish STAT3. In this study, turbot (Scophthalmus maximus) STAT3 gene was cloned and characterized for the first time. The turbot STAT3 full-length cDNA consists of 2355 nucleotides encoding a polypeptide of 784 amino acids with four conserved domains including STAT_int, STAT_alpha, STAT_bind and SH2 domain. The phylogenetic tree showed that turbot STAT3 shared the closest relationship with mandarin fish (Siniperca chuatsi) STAT3. The autoactivation experiment in yeast proved that turbot STAT3 was a strong transcription factor. The quantitative RT-PCR experiment indicated that Stat3 mRNA was expressed in widespread tissues with the highest expression levels in the liver. And the further expression patterns analysis revealed that turbot Stat3 expression levels were increased in liver, spleen, kidney of fish infected with Vibrio anguillarum and liver of fish infected with LCDV. Meantime, hepcidin, one of STAT3 target gene, was also up-regulated in liver of fish infected with two pathogens. These results suggested that turbot Stat3 may involved in the immune defense process as a transcription factor.

  1. Sol/Gel Processing Techniques for Glass Matrix Composites.

    DTIC Science & Technology

    1987-11-01

    development of a general technique (i.e., Pyrex is less susceptible to devitrification than SiO2 or TiO2 -SiO 2 ). In addition. the properties of these sol / gel ...of a sol / gel process for SIC 2 and SiO2 - TiO2 - together with a data base for their densification - are prerequisite to the successful fabrication of...S~%ad~ 5~ ~ ~ *~~~~;:>;::L-; 1: ’*~~’~ ’S. AFWL-TN-86-59 AFWL-TN- 86-59 00 SOL / GEL PROCESSING TECHNIQUES FOR GLASS MATRIX COMPOSITES 0) C. G

  2. Oxide Ceramic Fibers by the Sol-Gel Methods

    DTIC Science & Technology

    1989-02-10

    prepared by the sol-gel method . 3 Table 2. List of candidates for fibers via the sol-gel method . 4 Table 3. Solvents, raw materials and catalysts ...reaction chemistry. The synthesis method will be discussed in Section 3.1.3 Using commercially available precursors the production of lanthanum chromite via...AFWAL-TR-88-4199 OXIDE CERAMIC FIBERS BY THE SOL-GEL METHOD J. D. Mackenzie If) K. Ono The Regents of the University of California (Los Angeles) V

  3. Sol-gel derived PZT films doped with vanadium pentoxide

    SciTech Connect

    Shen Hongfang; Guo Qing; Zhao Zhiman; Cao Guozhong

    2009-11-15

    The present research investigated the sol-gel preparation, dielectric and ferroelectric properties of PZT films doped with 5 mol% vanadium oxide. Stable PZTV sols can be readily formed, and homogeneous, micrometer thick and pinhole-free PZTV films were obtained by using spin coating followed with rapid annealing. The X-ray diffraction patterns revealed that no parasitic or secondary phases were formed in the sol-gel PZT films with the addition of vanadium oxide. The material doped with vanadium pentoxide showed enhanced dielectric constant and remanent polarization with reduced loss tangent and coercive field.

  4. Silica scintillating materials prepared by sol-gel methods

    SciTech Connect

    Werst, D.W.; Sauer, M.C. Jr.; Cromack, K.R.; Lin, Y.; Tartakovsky, E.A.; Trifunac, A.D.

    1993-12-31

    Silica was investigated as a rad-hard alternative to organic polymer hosts for organic scintillators. Silica sol-gels were prepared by hydrolysis of tetramethoxysilane in alcohol solutions. organic dyes were incorporated into the gels by dissolving in methanol at the sol stage of gel formation. The silica sol-gel matrix is very rad-hard. The radiation stability of silica scintillators prepared by this method is dye-limited. Transient radioluminescence was measured following excitation with 30 ps pulses of 20 MeV electrons.

  5. Unphosphorylated STAT1 promotes sarcoma development through repressing expression of Fas and Bad and conferring apoptotic resistance

    PubMed Central

    Zimmerman, Mary A.; Rahman, Nur-Taz; Yang, Dafeng; Lahat, Guy; Lazar, Alexander J.; Pollock, Raphael; Lev, Dina; Liu, Kebin

    2012-01-01

    STAT1 exists in phosphorylated (pSTAT1) and unphosphorylated (uSTAT1) forms each regulated by IFN-γ. Although STAT1 is a key mediator of the IFN-γ signaling pathway, an essential component of the host cancer immunosurveillance system, STAT1 is also overexpressed in certain human cancers where the functions of pSTAT1 and uSTAT1 are ill-defined. Using a murine model of soft tissue sarcoma (STS), we demonstrate that disruption of the IFN effector molecule IRF8 decreases pSTAT1 and increases uSTAT1 in STS cells, thereby increasing their metastatic potential. We determined that the IRF8 gene promoter was hypermethylated frequently in human STS. An analysis of 123 human STS specimens revealed that high uSTAT1 levels in tumor cells was correlated with a reduction in disease-specific survival, whereas high pSTAT1 levels in tumor cells was correlated with an increase in disease-specific survival. In addition, uSTAT1 levels were negatively correlated with pSTAT1 levels in these STS specimens. Mechanistic investigations revealed that IRF8 suppressed STAT1 transcription by binding the STAT1 promoter. RNAi-mediated silencing of STAT1 in STS cells was sufficient to increase expression of the apoptotic mediators Fas and Bad and to elevate the sensitivity of STS cells to Fas-mediated apoptosis. Together, our findings show how the phosphorylation status of pSTAT1 determines its function as a tumor suppressor, with uSTAT1 acting as a tumor promoter that acts by elevating resistance to Fas-mediated apoptosis to promote immune escape. PMID:22805310

  6. Comment on “Stationary self-focusing of Gaussian laser beam in relativistic thermal quantum plasma” [Phys. Plasmas 20, 072703 (2013)

    SciTech Connect

    Habibi, M.; Ghamari, F.

    2014-06-15

    Patil and Takale in their recent article [Phys. Plasmas 20, 072703 (2013)], by evaluating the quantum dielectric response in thermal quantum plasma, have modeled the relativistic self-focusing of Gaussian laser beam in a plasma. We have found that there are some important shortcomings and fundamental mistakes in Patil and Takale [Phys. Plasmas 20, 072703 (2013)] that we give a brief description about them and refer readers to important misconception about the use of the Fermi temperature in quantum plasmas, appearing in Patil and Takale [Phys. Plasmas 20, 072703 (2013)].

  7. Effect of Chelating Agents on the Stability of Nano-TiO2 Sol Particles for Sol-Gel Coating.

    PubMed

    Maeng, Wan Young; Yoo, Mi

    2015-11-01

    Agglomeration of sol particles in a titanium alkoxide (tetrabutyl orthotitanate (TBOT), > 97%) solution during the hydrolysis and condensation steps makes the sol solution difficult to use for synthesizing homogeneous sol-gel coating. Here, we have investigated the effect of stabilizing agents (acetic acid and ethyl acetoacetate (EAcAc)) on the agglomeration of Ti alkoxide particles during hydrolysis and condensation in order to determine the optimized conditions for controlling the precipitation of TiO2 particles. The study was conducted at R(AC) ([acetic acid]/[TBOT]) = 0.1-5 and R(EAcAc)([EAcAc]/[TBOT]) = 0.05-0.65. We also studied the effects of a basic catalyst ethanolamine (ETA), water, and HCl on sol stability. The chelating ligands in the precursor sol were analyzed with FT-IR. The coating properties were examined by focused ion beam. The stabilizing agents (acetic acid and EAcAc) significantly influenced the agglomeration and precipitation of TBOT precursor particles during hydrolysis. As R(AC) and R(EAcAc) increased, the agglomeration remarkably decreased. The stability of the sol with acetic acid and EAcAc arises from the coordination of the chelating ligand to TBOT that hinders hydrolysis and condensation. A uniform fine coating (thickness: 30 nm) on stainless steel was obtained by using an optimized sol with R(AC) = 0.5 and R(EAcAc) = 0.65.

  8. Protein inhibitor of activated STAT3 inhibits adipogenic gene expression

    SciTech Connect

    Deng Jianbei; Hua Kunjie; Caveney, Erica J.; Takahashi, Nobuyuki; Harp, Joyce B. . E-mail: jharp@unc.edu

    2006-01-20

    Protein inhibitor of activated STAT3 (PIAS3), a cytokine-induced repressor of signal transducer and activator of transcription 3 (STAT3) and a modulator of a broad array of nuclear proteins, is expressed in white adipose tissue, but its role in adipogenesis is not known. Here, we determined that PIAS3 was constitutively expressed in 3T3-L1 cells at all stages of adipogenesis. However, it translocated from the nucleus to the cytoplasm 4 days after induction of differentiation by isobutylmethylxanthine, dexamethasone, and insulin (MDI). In ob/ob mice, PIAS3 expression was increased in white adipose tissue depots compared to lean mice and was found in the cytoplasm of adipocytes. Overexpression of PIAS3 in differentiating preadipocytes, which localized primarily to the nucleus, inhibited mRNA level gene expression of adipogenic transcription factors C/EBP{alpha} and PPAR{gamma}, as well as their downstream target genes aP2 and adiponectin. PIAS3 also inhibited C/EBP{alpha} promoter activation mediated specifically by insulin, but not dexamethasone or isobutylmethylxanthine. Taken together, these data suggest that PIAS3 may play an inhibitory role in adipogenesis by modulating insulin-activated transcriptional activation events. Increased PIAS3 expression in adipose tissue may play a role in the metabolic disturbances of obesity.

  9. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth.

    PubMed

    Harel, Sivan; Higgins, Claire A; Cerise, Jane E; Dai, Zhenpeng; Chen, James C; Clynes, Raphael; Christiano, Angela M

    2015-10-01

    Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells.

  10. JAK/STAT Pathways in Cytokine Signaling and Myeloproliferative Disorders

    PubMed Central

    Jatiani, Shashidhar S.; Baker, Stacey J.; Silverman, Lewis R.; Reddy, E. Premkumar

    2010-01-01

    Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Studies conducted over the past 10 to 15 years have revealed that hematopoietic cytokine receptor signaling is largely mediated by a family of tyrosine kinases termed Janus kinases (JAKs) and their downstream transcription factors, termed STATs (signal transducers and activators of transcription). Aberrations in these pathways, such as those caused by the recently identified JAK2V617F mutation and translocations of the JAK2 gene, are underlying causes of leukemias and other myeloproliferative disorders. This review discusses the role of JAK/STAT signaling in normal hematopoiesis as well as genetic abnormalities associated with myeloproliferative and myelodisplastic syndromes. This review also summarizes the status of several small molecule JAK2 inhibitors that are currently at various stages of clinical development. Several of these compounds appear to improve the quality of life of patients with myeloproliferative disorders by palliation of disease-related symptoms. However, to date, these agents do not seem to significantly affect bone marrow fibrosis, alter marrow histopathology, reverse cytopenias, reduce red cell transfusion requirements, or significantly reduce allele burden. These results suggest the possibility that additional mutational events might be associated with the development of these neoplasms, and indicate the need for combination therapies as the nature and significance of these additional molecular events is better understood. PMID:21442038

  11. Stat5 signaling specifies basal versus stress erythropoietic responses through distinct binary and graded dynamic modalities.

    PubMed

    Porpiglia, Ermelinda; Hidalgo, Daniel; Koulnis, Miroslav; Tzafriri, Abraham R; Socolovsky, Merav

    2012-08-01

    Erythropoietin (Epo)-induced Stat5 phosphorylation (p-Stat5) is essential for both basal erythropoiesis and for its acceleration during hypoxic stress. A key challenge lies in understanding how Stat5 signaling elicits distinct functions during basal and stress erythropoiesis. Here we asked whether these distinct functions might be specified by the dynamic behavior of the Stat5 signal. We used flow cytometry to analyze Stat5 phosphorylation dynamics in primary erythropoietic tissue in vivo and in vitro, identifying two signaling modalities. In later (basophilic) erythroblasts, Epo stimulation triggers a low intensity but decisive, binary (digital) p-Stat5 signal. In early erythroblasts the binary signal is superseded by a high-intensity graded (analog) p-Stat5 response. We elucidated the biological functions of binary and graded Stat5 signaling using the EpoR-HM mice, which express a "knocked-in" EpoR mutant lacking cytoplasmic phosphotyrosines. Strikingly, EpoR-HM mice are restricted to the binary signaling mode, which rescues these mice from fatal perinatal anemia by promoting binary survival decisions in erythroblasts. However, the absence of the graded p-Stat5 response in the EpoR-HM mice prevents them from accelerating red cell production in response to stress, including a failure to upregulate the transferrin receptor, which we show is a novel stress target. We found that Stat5 protein levels decline with erythroblast differentiation, governing the transition from high-intensity graded signaling in early erythroblasts to low-intensity binary signaling in later erythroblasts. Thus, using exogenous Stat5, we converted later erythroblasts into high-intensity graded signal transducers capable of eliciting a downstream stress response. Unlike the Stat5 protein, EpoR expression in erythroblasts does not limit the Stat5 signaling response, a non-Michaelian paradigm with therapeutic implications in myeloproliferative disease. Our findings show how the binary and

  12. The Tumor Suppressive Effects of HPP1 Are Mediated Through JAK-STAT-Interferon Signaling Pathways

    PubMed Central

    Hernandez, Jonathan M.; Elahi, Abul; Clark, Whalen; Humphries, Leigh Ann; Wang, Jian; Achille, Alex; Seto, Ed

    2015-01-01

    HPP1, a novel tumor suppressive epidermal growth factor (EGF)-like ligand, mediates its effects through signal transducer and activators of transcription (STAT) activation. We previously demonstrated the importance of STAT1 activation for HPP1 function; however the contribution of STAT2 remains unclear. We sought to delineate the components of JAK-STAT-interferon (IFN) signaling specifically associated with HPP1s biological effects. Using stable HPP1-HCT116 transfectants, expression analyses were performed by polymerase chain reaction (PCR)/western blotting while expression knockdowns were achieved using siRNA. Growth parameters evaluated included proliferation, cell cycle distribution, and anchorage-independent growth. STAT dimerization, translocation, and DNA binding were examined by reporter assays, fluorescent microscopy, and chromatin immunoprecipitation (ChIP), respectively. Forced expression of HPP1 in colon cancer cell lines results in the upregulation of total and activated levels of STAT2. We have also determined that JAK1 and JAK2 are activated in response to HPP1 overexpression, and are necessary for subsequent STAT activation. Overexpression of HPP1 was associated with significant increases in STAT1:STAT1 (p=0.007) and STAT1:STAT2 (p=0.036) dimer formation, as well as subsequent nuclear translocation. By ChIP, binding of activated STAT1 and STAT2 to the interferon-signaling regulatory element promoter sites of the selected genes, protein kinase RNA-activated (PKR), IFI44, and OAS1 was demonstrated. STAT2 knockdown resulted in partial abrogation of HPP1s growth suppressive activity with increased proliferation (p<0.0001), reduced G1/G0 phase cell cycle fraction, and a restoration of growth potential in soft agar (p<0.01). Presumably as a consequence of upregulation of IFN signaling elements, HPP1 overexpression resulted in an acquisition of exogenous IFN sensitivity. Physiologic doses of IFN-α resulted in a significant reduction in proliferation (p<0

  13. Comment on 'The diatomic dication CuZn{sup 2+} in the gas phase' [J. Chem. Phys. 135, 034306 (2011)

    SciTech Connect

    Fiser, Jiri; Diez, Reinaldo Pis; Franzreb, Klaus; Alonso, Julio A.

    2013-02-21

    In this Comment, the density functional theory (DFT) calculations carried out by Diez et al. [J. Chem. Phys. 135, 034306 (2011)] are revised within the framework of the coupled-cluster single double triple method. These more sophisticated calculations allow us to show that the {sup 2}{Sigma}{sup +} electronic ground state of CuZn{sup 2+}, characterized as the metastable ground state by DFT calculations, is a repulsive state instead. The {sup 2}{Delta} and {sup 2}{Pi} metastable states of CuZn{sup 2+}, on the other hand, should be responsible for the formation mechanism of the dication through the near-resonant electron transfer CuZn{sup +}+ Ar{sup +}{yields} CuZn{sup 2+}+ Ar reaction.

  14. Comment on “Deterministic six states protocol for quantum communication” [Phys. Lett. A 358 (2006) 85

    NASA Astrophysics Data System (ADS)

    El-Orany, Faisal A. A.

    2010-02-01

    In [J.S. Shaari, M. Lucamarini, M.R.B. Wahiddin, Phys. Lett. A 358 (2006) 85] the deterministic six states protocol (6DP) for quantum communication has been developed. This protocol is based on three mutually unbiased bases and four encoding operators. Information is transmitted between the users via two qubits from different bases. Three attacks have been studied; namely intercept-resend attack (IRA), double-CNOT attack (2CNOTA) and quantum man-in-the-middle attack. In this Letter, we show that the IRA and 2CNOTA are not properly addressed. For instance, we show that the probability of detecting Eve in the control mode of the IRA is 70% instead of 50% in the previous study. Moreover, in the 2CNOTA, Eve can only obtain 50% of the data not all of it as argued earlier.

  15. Comment on "Unexpected size effect in the thermopower of thin-film stripes" [J. Appl. Phys. 110, 083709 (2011)

    NASA Astrophysics Data System (ADS)

    Szakmany, Gergo P.; Orlov, Alexei O.; Bernstein, Gary H.; Porod, Wolfgang

    2014-06-01

    In a recent article, Sun et al. [J. Appl. Phys. 110, 083709 (2011)] claim to measure a size-dependent thermoelectric effect in a micron-scale single-metal thermocouple. In this Comment, we demonstrate that the observed phenomenon is not due to a size-dependent Seebeck effect as claimed, but is rather wire-size-dependent heat transport that causes unequal heating at the bonding pads. As a result, the bonding pads are at two different temperatures, and the observed voltage corresponds to a thermoelectric effect of a parasitic thermocouple formed between their metal structure and the bonding-pad wires. We provide simulations and suggest a control experiment based on their structure that supports our contention that the observation depends on width-dependent heat transport in the wires.

  16. Activation of the Notch1/STAT3/Twist signaling axis promotes gastric cancer progression.

    PubMed

    Hsu, Kai-Wen; Hsieh, Rong-Hong; Huang, Kuo-Hung; Fen-Yau Li, Anna; Chi, Chin-Wen; Wang, Tzu-Yin; Tseng, Min-Jen; Wu, Kou-Juey; Yeh, Tien-Shun

    2012-08-01

    Gastric carcinoma is one of the most common malignancies and a lethal cancer in the world. Notch signaling and transcription factors STAT3 (signal transducer and activator of transcription 3) and Twist regulate tumor development and are critical regulators of gastric cancer progression. Herein, the relationship among Notch, STAT3 and Twist pathways in the control of gastric cancer progression was studied. We found that Twist and phosphorylated STAT3 levels were promoted by the activated Notch1 receptor in human stomach adenocarcinoma SC-M1, embryonic kidney HEK293 and erythroleukemia K562 cells. Notch1 signaling dramatically induced Twist promoter activity through a C promoter binding factor-1-independent manner and STAT3 phosphorylation. Overexpression of Notch1 receptor intracellular domain (N1IC) enhanced the interaction between nuclear STAT3 and Twist promoter in cells. Gastric cancer progression of SC-M1 cells was promoted by N1IC through STAT3 phosphorylation and Twist expression including colony formation, migration and invasion. STAT3 regulated gastric cancer progression of SC-M1 cells via Twist. N1IC also elevated the progression of other gastric cancer cells such as AGS and KATO III cells through STAT3 and Twist. The N1IC-promoted tumor growth and lung metastasis of SC-M1 cells in mice were suppressed by the STAT3 inhibitor JSI-124 and Twist knockdown. Furthermore, Notch1 and Notch ligand Jagged1 expressions were significantly associated with phosphorylated STAT3 and Twist levels in gastric cancer tissues of patients. Taken together, these results suggest that Notch1/STAT3/Twist signaling axis is involved in progression of human gastric cancer and modulation of this cascade has potential for the targeted combination therapy.

  17. Death-associated protein kinase controls STAT3 activity in intestinal epithelial cells.

    PubMed

    Chakilam, Saritha; Gandesiri, Muktheshwar; Rau, Tilman T; Agaimy, Abbas; Vijayalakshmi, Mahadevan; Ivanovska, Jelena; Wirtz, Ralph M; Schulze-Luehrmann, Jan; Benderska, Natalya; Wittkopf, Nadine; Chellappan, Ajithavalli; Ruemmele, Petra; Vieth, Michael; Rave-Fränk, Margret; Christiansen, Hans; Hartmann, Arndt; Neufert, Clemens; Atreya, Raja; Becker, Christoph; Steinberg, Pablo; Schneider-Stock, Regine

    2013-03-01

    The TNF-IL-6-STAT3 pathway plays a crucial role in promoting ulcerative colitis-associated carcinoma (UCC). To date, the negative regulation of STAT3 is poorly understood. Interestingly, intestinal epithelial cells of UCC in comparison to ulcerative colitis show high expression levels of anti-inflammatory death-associated protein kinase (DAPK) and low levels of pSTAT3. Accordingly, epithelial DAPK expression was enhanced in STAT3(IEC-KO) mice. To unravel a possible regulatory mechanism, we used an in vitro TNF-treated intestinal epithelial cell model. We identified a new function of DAPK in suppressing TNF-induced STAT3 activation as DAPK siRNA knockdown and treatment with a DAPK inhibitor potentiated STAT3 activation, IL-6 mRNA expression, and secretion. DAPK attenuated STAT3 activity directly by physical interaction shown in three-dimensional structural modeling. This model suggests that DAPK-induced conformational changes in the STAT3 dimer masked its nuclear localization signal. Alternatively, pharmacological inactivation of STAT3 led to an increase in DAPK mRNA and protein levels. Chromatin immunoprecipitation showed that STAT3 restricted DAPK expression by promoter binding, thereby reinforcing its own activation by inducing IL-6. This novel negative regulation principle might balance TNF-induced inflammation and seems to play an important role in the inflammation-associated transformation process as confirmed in an AOM+DSS colon carcinogenesis mouse model. DAPK as a negative regulator of STAT3 emerges as therapeutic option in the treatment of ulcerative colitis and UCC.

  18. The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling

    PubMed Central

    Weigl, Julia; De Nicola, Gina Rosalinda; Canistro, Donatella; Paolini, Moreno; Iori, Renato; Rascle, Anne

    2016-01-01

    Sulforaphane (SFN) and moringin (GMG-ITC) are edible isothiocyanates present as glucosinolate precursors in cruciferous vegetables and in the plant Moringa oleifera respectively, and recognized for their chemopreventive and medicinal properties. In contrast to the well-studied SFN, little is known about the molecular pathways targeted by GMG-ITC. We investigated the ability of GMG-ITC to inhibit essential signaling pathways that are frequently upregulated in cancer and immune disorders, such as JAK/STAT and NF-κB. We report for the first time that, similarly to SFN, GMG-ITC in the nanomolar range suppresses IL-3-induced expression of STAT5 target genes. GMG-ITC, like SFN, does not inhibit STAT5 phosphorylation, suggesting a downstream inhibitory event. Interestingly, treatment with GMG-ITC or SFN had a limited inhibitory effect on IFNα-induced STAT1 and STAT2 activity, indicating that both isothiocyanates differentially target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar range is a more potent inhibitor of TNF-induced NF-κB activity than SFN. Finally, using a cellular system mimicking constitutive active STAT5-induced cell transformation, we demonstrated that SFN can reverse the survival and growth advantage mediated by oncogenic STAT5 and triggers cell death, therefore providing experimental evidence of a cancer chemopreventive activity of SFN. This work thus identified STAT5, and to a lesser extent STAT1/STAT2, as novel targets of moringin. It also contributes to a better understanding of the biological activities of the dietary isothiocyanates GMG-ITC and SFN and further supports their apparent beneficial role in the prevention of chronic illnesses such as cancer, inflammatory diseases and immune disorders. PMID:27304884

  19. The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling.

    PubMed

    Michl, Carina; Vivarelli, Fabio; Weigl, Julia; De Nicola, Gina Rosalinda; Canistro, Donatella; Paolini, Moreno; Iori, Renato; Rascle, Anne

    2016-01-01

    Sulforaphane (SFN) and moringin (GMG-ITC) are edible isothiocyanates present as glucosinolate precursors in cruciferous vegetables and in the plant Moringa oleifera respectively, and recognized for their chemopreventive and medicinal properties. In contrast to the well-studied SFN, little is known about the molecular pathways targeted by GMG-ITC. We investigated the ability of GMG-ITC to inhibit essential signaling pathways that are frequently upregulated in cancer and immune disorders, such as JAK/STAT and NF-κB. We report for the first time that, similarly to SFN, GMG-ITC in the nanomolar range suppresses IL-3-induced expression of STAT5 target genes. GMG-ITC, like SFN, does not inhibit STAT5 phosphorylation, suggesting a downstream inhibitory event. Interestingly, treatment with GMG-ITC or SFN had a limited inhibitory effect on IFNα-induced STAT1 and STAT2 activity, indicating that both isothiocyanates differentially target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar range is a more potent inhibitor of TNF-induced NF-κB activity than SFN. Finally, using a cellular system mimicking constitutive active STAT5-induced cell transformation, we demonstrated that SFN can reverse the survival and growth advantage mediated by oncogenic STAT5 and triggers cell death, therefore providing experimental evidence of a cancer chemopreventive activity of SFN. This work thus identified STAT5, and to a lesser extent STAT1/STAT2, as novel targets of moringin. It also contributes to a better understanding of the biological activities of the dietary isothiocyanates GMG-ITC and SFN and further supports their apparent beneficial role in the prevention of chronic illnesses such as cancer, inflammatory diseases and immune disorders.

  20. Epithelial defect in prostates of Stat5a-null mice.

    PubMed

    Nevalainen, M T; Ahonen, T J; Yamashita, H; Chandrashekar, V; Bartke, A; Grimley, P M; Robinson, G W; Hennighausen, L; Rui, H

    2000-07-01

    The transcription factor Stat5a critically mediates prolactin (PRL)-induced mammary gland development and lactogenesis. PRL also stimulates growth and differentiation of prostate tissue. Specifically, hyperprolactinemia gives rise to prostate hyperplasia, and prostate size is reduced in PRL-deficient mice. We therefore investigated the importance of Stat5a for prostate development and function by examining Stat5a-null mice. The absence of Stat5a in mice was associated with a distinct prostate morphology characterized by an increased prevalence of local disorganization within acinar epithelium of ventral prostates. Affected acini were typically filled with desquamated, granular epithelial cells that had become embedded in dense, coagulated secretory material. These features were reminiscent of acinar cyst formation and degeneration frequently observed in human benign prostate hyperplasia, however, cystic changes in prostate acini of Stat5a-deficient mice were not associated with increased prostate size or morphologic hallmarks of epithelial hyperplasia. Instead, immunohistochemistry of the prostate-specific secretory marker, probasin, suggested that hypersecretory function of the epithelium could underlie local congestion and cyst formation in prostates of Stat5a-null mice. Serum testosterone and PRL levels were normal in Stat5a knockout mice, but prostate PRL receptor expression was reduced as determined by immunohistochemistry. Expression levels or activation states of other PRL signal transduction proteins, including Stat5b, Stat3, Stat1, ERK1, and ERK2 were not altered. The present study offers the first evidence for a direct role of Stat5a in the maintenance of normal tissue architecture and function of the mouse prostate.

  1. Production of continuous mullite fiber via sol-gel processing

    NASA Technical Reports Server (NTRS)

    Tucker, Dennis S.; Sparks, J. Scott; Esker, David C.

    1990-01-01

    The development of a continuous ceramic fiber which could be used in rocket engine and rocket boosters applications was investigated at the Marshall Space Flight Center. Methods of ceramic fiber production such as melt spinning, chemical vapor deposition, and precursor polymeric fiber decomposition are discussed and compared with sol-gel processing. The production of ceramics via the sol-gel method consists of two steps, hydrolysis and polycondensation, to form the preceramic, followed by consolidation into the glass or ceramic structure. The advantages of the sol-gel method include better homogeneity and purity, lower preparation temperature, and the ability to form unique compositions. The disadvantages are the high cost of raw materials, large shrinkage during drying and firing which can lead to cracks, and long processing times. Preparation procedures for aluminosilicate sol-gel and for continuous mullite fibers are described.

  2. Martian Dust Devil Movie, Phoenix Sol 104

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Surface Stereo Imager on NASA's Phoenix Mars Lander caught this dust devil in action west of the lander in four frames shot about 50 seconds apart from each other between 11:53 a.m. and 11:56 a.m. local Mars time on Sol 104, or the 104th Martian day of the mission, Sept. 9, 2008.

    Dust devils have not been detected in any Phoenix images from earlier in the mission, but at least six were observed in a dozen images taken on Sol 104.

    Dust devils are whirlwinds that often occur when the Sun heats the surface of Mars, or some areas on Earth. The warmed surface heats the layer of atmosphere closest to it, and the warm air rises in a whirling motion, stirring dust up from the surface like a miniature tornado.

    The dust devil visible in this sequence was about 1,000 meters (about 3,300 feet) from the lander when the first frame was taken, and had moved to about 1,700 meters (about 5,600 feet) away by the time the last frame was taken about two and a half minutes later. The dust devil was moving westward at an estimated speed of 5 meters per second (11 miles per hour), which is similar to typical late-morning wind speed and direction indicated by the telltale wind gauge on Phoenix.

    This dust devil is about 5 meters (16 feet) in diameter. This is much smaller than dust devils that have been observed by NASA's Mars Exploration Rover Spirit much closer to the equator. It is closer in size to dust devils seen from orbit in the Phoenix landing region, though still smaller than those..

    The image has been enhanced to make the dust devil easier to see. Some of the frame-to-frame differences in the appearance of foreground rocks is because each frame was taken through a different color filter.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  3. Erratum to "Solar Sources and Geospace Consequences of Interplanetary Magnetic Clouds Observed During Solar Cycle 23-Paper 1" [J. Atmos. Sol.-Terr. Phys. 70(2-4) (2008) 245-253

    NASA Technical Reports Server (NTRS)

    Gopalswamy, N.; Akiyama, S.; Yashiro, S.; Michalek, G.; Lepping, R. P.

    2009-01-01

    One of the figures (Fig. 4) in "Solar sources and geospace consequences of interplanetary magnetic Clouds observed during solar cycle 23 -- Paper 1" by Gopalswamy et al. (2008, JASTP, Vol. 70, Issues 2-4, February 2008, pp. 245-253) is incorrect because of a software error in t he routine that was used to make the plot. The source positions of various magnetic cloud (MC) types are therefore not plotted correctly.

  4. Notes on "Soliton solutions by Darboux transformation and some reductions for a new Hamiltonian lattice hierarchy" [Phys. Scr. 82 (2010) 015008

    NASA Astrophysics Data System (ADS)

    Xu, Xi-Xiang

    We demonstrate that the Darboux transformation in the paper "Soliton solutions by Darboux transformation and some reductions for a new Hamiltonian lattice hierarchy" [Phys. Scr. 82 (2010) 015008] is incorrect, and establish a correct Darboux transformation.

  5. Stat3 Activation in Murine Colitis Induced by Enterotoxigenic Bacteroides fragilis

    PubMed Central

    Wick, Elizabeth C.; Rabizadeh, Shervin; Albesiano, Emilia; Wu, XinQun; Wu, Shaoguang; Chan, June; Rhee, Ki-Jong; Ortega, Guillermo; Huso, David L.; Pardoll, Drew; Housseau, Franck; Sears, Cynthia L.

    2014-01-01

    Background Enterotoxigenic Bacteroides fragilis (ETBF), a molecular subclass of the common human commensal, B. fragilis, has been associated with inflammatory bowel disease. ETBF colitis is characterized by the activation of Stat3 and a Th17 immune response in the colonic mucosa. This study was designed to investigate the time course and cellular distribution of Stat3 activation in ETBF-colonized mice. Methods C57BL/6 wild-type, C57BL/6Stat3ΔIEC, or Rag-1 mice were inoculated with saline, nontoxigenic B. fragilis or ETBF. Histologic diagnosis and mucosal Stat activation (immunohistochemistry, Western blot, and/or electrophorectic mobility shift assay) were evaluated over time (6–24 h, 1–7 d, and 1–18 mo after inoculation). Mucosal permeability was evaluated at 16 hours, 1 day, and 3 days. Mucosal immune responses were evaluated at 1 week, and 12 and 18 months. Results ETBF induced rapid-onset colitis that persisted for up to 1 year. Stat3 activation (pStat3) was noted in the mucosal immune cells within 16 hours, with colonic epithelial cell activation evident at 24 hours after inoculation. ETBF-induced increased mucosal permeability was first observed at 24 hours after inoculation, after which the initial immune cell pStat3 activation was noted. Immune cell pStat3 was present in the absence of epithelial pStat3 (C57BL/ 6Stat3ΔIEC). Epithelial pStat3 was present in the absence of T and B cells (Rag-1 mice). pStat3 persisted in the epithelial and immune cells for 1 year, characterized by isolated pStat3-positive cell clusters, with varying intensity distributed through the proximal and distal colon. Similarly, mucosal Th17 immune responses persisted for up to 1 year. Loss of fecal ETBF colonization was associated with the loss of mucosal pStat3 and Th17 immune responses. Conclusions ETBF rapidly induces immune cell pStat3, which is independent of epithelial pStat3. This occurs before ETBF-induced mucosal permeability, suggesting that ETBF, likely through B

  6. Electrochemical and spectroscopic characterization of surface sol-gel processes.

    PubMed

    Chen, Xiaohong; Wilson, George S

    2004-09-28

    (3-Mercaptopropyl)trimethoxysilane (MTS) forms a unique film on a platinum substrate by self-assembly and sol-gel cross-linking. The gelating and drying states of the self-assembled MTS sol-gel films were probed by use of electrochemical and spectroscopic methods. The thiol moiety was the only active group within the sol-gel network. Gold nanoparticles were employed to detect the availability of the thiol group and their interaction further indicated the physicochemical states of the sol-gel inner structure. It was found that the thiol groups in the open porous MTS aerogel matrix were accessible to the gold nanoparticles while thiol groups in the compact MTS xerogel network were not accessible to the gold nanoparticles. The characteristics of the sol-gel matrix change with time because of its own irreversible gelating and drying process. The present work provides direct evidence of gold nanoparticle binding with thiol groups within the sol-gel structures and explains the different permeability of "aerogel" and "xerogel" films of MTS on the basis of electrochemical and spectroscopic results. Two endogenous species, hydrogen peroxide and ascorbic acid, were used to test the permeability of the self-assembled sol-gel film in different states. The MTS xerogel film on the platinum electrode was extremely selective against ascorbic acid while maintaining high sensitivity to hydrogen peroxide in contrast to the relatively high permeability of ascorbic acid in the MTS aerogel film. This study showed the potential of the MTS sol-gel film as a nanoporous material in biosensor development.

  7. New developments for sol-gel film and fiber processing

    SciTech Connect

    Hurd, A.J.

    1995-03-01

    New insights into the development of microstructure in sol-gel films have recently been revealed by several diagnostic techniques, including imaging ellipsometry, {open_quotes}chemical imaging{close_quotes} by fluorescent tracers, light scattering from capillary waves, and finite-element modeling. The evolution of porosity during the continuous transition from dilute sol to porous solid in restricted geometries such as films and fibers is becoming clearer through fundamental understanding of evaporation dynamics and capillarity.

  8. Prospects of sol-gel technology towards luminescent materials

    NASA Astrophysics Data System (ADS)

    Reisfeld, R.

    2001-02-01

    Sol-gel method for producing glasses or glass films at relatively low temperature allows incorporation of a large number of inorganic and organic additives during the process of glass formation. We outline some of the sophisticated products and devices obtained by the sol-gel method. Luminecence solar concentrators, tunable lasers in the visible part of the spectrum, active waveguides, semiconductor particles and sensors for environmental impurities.

  9. Topical Meeting on Optical Bistability Held at Rochester, New York on 15-17 June 1983.

    DTIC Science & Technology

    1983-01-01

    Republic of Germany, and P. Meystre and E. Vignes , vax-Planck-lnstitut fOr Quantenoptil:, Federal Republic of Germa,,y. Optical bistability without...Moss, Phys. Stat. Sol . (b) 101 555 (1980) Of.---.. * -..-...***.*4 ME. .17. 17~ . .. , J , 1.0 ,ThA3-4 -2.9 0.42 > HF laser line 3.0 .. 0.40 31...interaction and the local field correction are to be represented. . °. . . ., ThB29-2 Ref erences 1. J. Goll and H. Haken, Phys. Stat. Sol ., (6) 101, 489

  10. A novel platinum compound inhibits constitutive Stat3 signaling and induces cell cycle arrest and apoptosis of malignant cells.

    PubMed

    Turkson, James; Zhang, Shumin; Mora, Linda B; Burns, Audrey; Sebti, Said; Jove, Richard

    2005-09-23

    Previous studies have established constitutive activation of Stat3 protein as one of the molecular changes required for tumorigenesis. To develop novel therapeutics for tumors harboring constitutively active Stat3, compounds from the NCI 2000 diversity set were evaluated for inhibition of Stat3 DNA-binding activity in vitro. Of these, a novel platinum (IV) compound, IS3 295, interacted with Stat3 and inhibited its binding to specific DNA-response elements. Further analysis suggested noncompetitive-type kinetics for the inhibition of Stat3 binding to DNA. In human and mouse tumor cell lines with constitutively active Stat3, IS3 295 selectively attenuated Stat3 signaling, thereby inducing cell growth arrest at G0/G1 phase and apoptosis. Moreover, in transformed cells, IS3 295 repressed expression of cyclin D1 and bcl-xL, two of the known Stat3-regulated genes that are overexpressed in malignant cells, suggesting that IS3 295 mediates anti-tumor cell activity in part by blocking Stat3-mediated sub-version of cell growth and apoptotic signals. Together, our findings provide evidence for the inhibition of Stat3 activity and biological functions by IS3 295 through interaction with Stat3 protein. This study represents a significant advance in small molecule-based approaches to target Stat3 and suggests potential new applications for platinum (IV) complexes as modulators of the Stat3 pathway for cancer therapy.

  11. Sodium orthovanadate suppresses palmitate-induced cardiomyocyte apoptosis by regulation of the JAK2/STAT3 signaling pathway.

    PubMed

    Liu, Jing; Fu, Hui; Chang, Fen; Wang, Jinlan; Zhang, Shangli; Caudle, Yi; Zhao, Jing; Yin, Deling

    2016-05-01

    Elevated circulatory free fatty acids (FFAs) especially saturated FFAs, such as palmitate (PA), are detrimental to the heart. However, mechanisms responsible for this phenomenon remain unknown. Here, the role of JAK2/STAT3 in PA-induced cytotoxicity was investigated in cardiomyocytes. We demonstrate that PA suppressed the JAK2/STAT3 pathway by dephosphorylation of JAK2 (Y1007/1008) and STAT3 (Y705), and thus blocked the translocation of STAT3 into the nucleus. Conversely, phosphorylation of S727, another phosphorylated site of STAT3, was increased in response to PA treatment. Pretreatment of JNK inhibitor, but not p38 MAPK inhibitor, inhibited STAT3 (S727) activation induced by PA and rescued the phosphorylation of STAT3 (Y705). The data suggested that JNK may be another upstream factor regulating STAT3, and verified the important function of P-STAT3 (Y705) in PA-induced cardiomyocyte apoptosis. Sodium orthovanadate (SOV), a protein tyrosine phosphatase inhibitor, obviously inhibited PA-induced apoptosis by restoring JAK2/STAT3 pathways. This effect was diminished by STAT3 inhibitor Stattic. Collectively, our data suggested a novel mechanism that the inhibition of JAK2/STAT3 activation was responsible for palmitic lipotoxicity and SOV may act as a potential therapeutic agent by targeting JAK2/STAT3 in lipotoxic cardiomyopathy treatment.

  12. Comment on "Fe2: As simple as a Herculean labour. Neutral (Fe2), cationic (Fe2+), and anionic (Fe2-) species" [J. Chem. Phys. 142, 244304 (2015)

    NASA Astrophysics Data System (ADS)

    Hoyer, Chad E.; Li Manni, Giovanni; Truhlar, Donald G.; Gagliardi, Laura

    2016-01-01

    A recent paper on Fe2 [A. Kalemos, J. Chem. Phys. 142, 244304 (2015)] critiqued our previous work on the system [Hoyer et al., J. Chem. Phys. 141, 204309 (2014)]. In this comment, we explain the nature of our previously reported potential energy curve for Fe2 and we discuss our computed properties for Fe2. Additionally, we fix a labeling error that was present in our previous work, although this error is unrelated to the main point of discussion.

  13. JAB1 regulates unphosphorylated STAT3 DNA-binding activity through protein–protein interaction in human colon cancer cells

    SciTech Connect

    Nishimoto, Arata; Kugimiya, Naruji; Hosoyama, Toru; Enoki, Tadahiko; Li, Tao-Sheng; Hamano, Kimikazu

    2013-08-30

    Highlights: •JAB1 interacted with unphosphorylated STAT3 in the nucleus. •JAB1 knockdown tended to increase nuclear STAT3 expression. •JAB1 knockdown significantly decreased unphosphorylated STAT3 DNA-binding activity. •JAB1 knockdown significantly decreased MDR1, NANOG, and VEGF expressions. •Nuclear JAB1, but not nuclear STAT3, correlated with STAT3 DNA-binding activity. -- Abstract: Recent studies have revealed that unphosphorylated STAT3 forms a dimer, translocates to the nucleus, binds to the STAT3 binding site, and activates the transcription of STAT3 target genes, thereby playing an important role in oncogenesis in addition to phosphorylated STAT3. Among signaling steps of unphosphorylated STAT3, nuclear translocation and target DNA-binding are the critical steps for its activation. Therefore, elucidating the regulatory mechanism of these signaling steps of unphosphorylated STAT3 is a potential step in the discovery of a novel cancer drug. However, the mechanism of unphosphorylated STAT3 binding to the promoter of target genes remains unclear. In this study, we focused on Jun activation domain-binding protein 1 (JAB1) as a candidate protein that regulates unphosphorylated STAT3 DNA-binding activity. Initially, we observed that both unphosphorylated STAT3 and JAB1 existed in the nucleus of human colon cancer cell line COLO205 at the basal state (no cytokine stimulation). On the other hand, phosphorylated STAT3 did not exist in the nucleus of COLO205 cells at the basal state. Immunoprecipitation using nuclear extract of COLO205 cells revealed that JAB1 interacted with unphosphorylated STAT3. To investigate the effect of JAB1 on unphosphorylated STAT3 activity, RNAi studies were performed. Although JAB1 knockdown tended to increase nuclear STAT3 expression, it significantly decreased unphosphorylated STAT3 DNA-binding activity. Subsequently, JAB1 knockdown significantly decreased the expression levels of MDR1, NANOG, and VEGF, which are STAT3 target

  14. Immune deficiency vs. immune excess in inflammatory bowel diseases-STAT3 as a rheo-STAT of intestinal homeostasis.

    PubMed

    Leppkes, Moritz; Neurath, Markus F; Herrmann, Martin; Becker, Christoph

    2016-01-01

    Genome-wide association studies have provided many genetic alterations, conferring susceptibility to multifactorial polygenic diseases, such as inflammatory bowel diseases. Yet, how specific genetic alterations functionally affect intestinal inflammation often remains elusive. It is noteworthy that a large overlap of genes involved in immune deficiencies with those conferring inflammatory bowel disease risk has been noted. This has provided new arguments for the debate on whether inflammatory bowel disease arises from either an excess or a deficiency in the immune system. In this review, we highlight the functional effect of an inflammatory bowel disease-risk allele, which cannot be deduced from genome-wide association studies data alone. As exemplified by the transcription factor signal transducer and activator of transcription 3 (STAT3), we show that a single gene can have a plethora of effects in various cell types of the gut. These effects may individually contribute to the restoration of intestinal homeostasis on the one hand or pave the way for excessive immunopathology on the other, as an inflammatory "rheo-STAT".

  15. Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma.

    PubMed

    Sibbesen, Nina A; Kopp, Katharina L; Litvinov, Ivan V; Jønson, Lars; Willerslev-Olsen, Andreas; Fredholm, Simon; Petersen, David L; Nastasi, Claudia; Krejsgaard, Thorbjørn; Lindahl, Lise M; Gniadecki, Robert; Mongan, Nigel P; Sasseville, Denis; Wasik, Mariusz A; Iversen, Lars; Bonefeld, Charlotte M; Geisler, Carsten; Woetmann, Anders; Odum, Niels

    2015-08-21

    Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL). However, it remains only partially understood how Jak3/STAT activation promotes lymphomagenesis. Recently, non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of this malignancy. Here, we show that (i) malignant T cells display a decreased expression of a tumor suppressor miRNA, miR-22, when compared to non-malignant T cells, (ii) STAT5 binds the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA.

  16. Sol-gel-based biosensing applied to medicinal science.

    PubMed

    Moreira, Felismina T C; Moreira-Tavares, Ana P; Sales, M Goreti F

    2015-01-01

    Biosensors have opened new horizons in biomedical analysis, by ensuring increased assay speed and flexibility, and allowing point-of-care applications, multi-target analyses, automation and reduced costs of testing. This has been a result of many studies merging nanotechnology with biochemistry over the years, thereby enabling the creation of more suitable environments to biological receptors and their substitution by synthetic analogue materials. Sol-gel chemistry, among other materials, is deeply involved in this process. Sol-gel processing allows the immobilization of organic molecules, biomacromolecules and cells maintaining their properties and activities, permitting their integration into different transduction devices, of electrochemical or optical nature, for single or multiple analyses. Sol-gel also allows to the production of synthetic materials mimicking the activity of natural receptors, while bringing advantages, mostly in terms of cost and stability. Moreover, the biocompatibility of sol-gel materials structures of biological nature allowed the use of these materials in emerging in vivo applications. In this chapter, biosensors for biomedical applications based on sol-gel derived composites are presented, compared and described, along with current emerging applications in vivo, concerning drug delivery or biomaterials. Sol-gel materials are shown as a promising tool for current, emerging and future medical applications.

  17. New Record Five-Wheel Drive, Spirit's Sol 1856

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Spirit used its navigation camera to take the images that have been combined into this stereo, 180-degree view of the rover's surroundings during the 1,856th Martian day, or sol, of Spirit's surface mission (March 23, 2009). The center of the view is toward the west-southwest.

    The rover had driven 25.82 meters (84.7 feet) west-northwestward earlier on Sol 1856. This is the longest drive on Mars so far by a rover using only five wheels. Spirit lost the use of its right-front wheel in March 2006. Before Sol 1856, the farthest Spirit had covered in a single sol's five-wheel drive was 24.83 meters (81.5 feet), on Sol 1363 (Nov. 3, 2007).

    The Sol 1856 drive made progress on a route planned for taking Spirit around the western side of the low plateau called 'Home Plate.' A portion of the northwestern edge of Home Plate is prominent in the left quarter of this image, toward the south.

    This view is presented as a cylindrical projection with geometric seam correction.

  18. The effects of the Snowflake Divertor on upstream SOL profiles

    NASA Astrophysics Data System (ADS)

    Tsui, C. K.; Boedo, J. A.; Coda, S.; Labit, B.; Maurizio, R.; Nespoli, F.; Reimerdes, H.; Theiler, C.; Spolaore, M.; Vianello, N.; Lunt, T.; Vijvers, W. A. J.; Walkden, N.; the EUROfusion MST1 Team Team; the TCV Team Team

    2016-10-01

    The Snowflake Divertor creates separated volumes within the SOL and divertor that feature strikingly different ne, Te profiles, and decay lengths, as measured with a scanning probe. Profiles were taken at the outer midplane of TCV plasmas with snowflake divertors as well as just above the X-points within the region of enhanced βpol. Density shoulders in the far SOL in single null plasmas are relaxed by secondary X-points, while effects are more complex in the near SOL. These changes were observed whether the secondary X-point was placed in the low field side SOL, or in the high field side SOL. Additionally, target profiles measured with IR camera and Langmiur probes that were taken in the divertor leg opposite the secondary X-point also show features on the flux surface corresponding to the secondary X-point. Fluctuation statistics from the reciprocating probe as well as comparisons made between upstream and downstream measurements are considered for their implications on SOL transport. Support from EUROfusion Grant 633053 and US DOE Grant DE-SC0010529 are gratefully acknowledged.

  19. STAT3 integrates cytokine and neurotrophin signals to promote sympathetic axon regeneration

    PubMed Central

    Pellegrino, Michael J.; Habecker, Beth A.

    2013-01-01

    The transcription factor STAT3 has been implicated in axon regeneration. Here we investigate a role for STAT3 in sympathetic nerve sprouting after myocardial infarction (MI) - a common injury in humans. We show that NGF stimulates serine phosphorylation (S727) of STAT3 in sympathetic neurons via ERK1/2, in contrast to cytokine phosphorylation of Y705. Maximal sympathetic axon regeneration in vitro requires phosphorylation of both S727 and Y705. Furthermore, cytokine signaling is necessary for NGF-induced sympathetic nerve sprouting in the heart after MI. Transfection studies in neurons lacking STAT3 suggest two independent pools of STAT3, phosphorylated on either S727 or Y705, that regulate sympathetic regeneration via both transcriptional and non-transcriptional means. Additional data identify STAT3-microtubule interactions that may complement the well-characterized role of STAT3 stimulating regeneration associated genes. These data show that STAT3 is critical for sympathetic axon regeneration in vitro and in vivo, and identify a novel non-transcriptional mode of action. PMID:23831387

  20. Coregulation of genetic programs by the transcription factors NFIB and STAT5.

    PubMed

    Robinson, Gertraud W; Kang, Keunsoo; Yoo, Kyung Hyun; Tang, Yong; Zhu, Bing-Mei; Yamaji, Daisuke; Colditz, Vera; Jang, Seung Jian; Gronostajski, Richard M; Hennighausen, Lothar

    2014-05-01

    Mammary-specific genetic programs are activated during pregnancy by the common transcription factor signal transducer and activator of transcription (STAT) 5. More than one third of these genes carry nuclear factor I/B (NFIB) binding motifs that coincide with STAT5 in vivo binding, suggesting functional synergy between these two transcription factors. The role of NFIB in this governance was investigated in mice from which Nfib had been inactivated in mammary stem cells or in differentiating alveolar epithelium. Although NFIB was not required for alveolar expansion, the combined absence of NFIB and STAT5 prevented the formation of functional alveoli. NFIB controlled the expression of mammary-specific and STAT5-regulated genes and chromatin immunoprecipitation-sequencing established STAT5 and NFIB binding at composite regulatory elements containing histone H3 lysine dimethylation enhancer marks and progesterone receptor binding. By integrating previously published chromatin immunoprecipitation-sequencing data sets, the presence of NFIB-STAT5 modules in other cell types was investigated. Notably, genomic sites bound by NFIB in hair follicle stem cells were also occupied by STAT5 in mammary epithelium and coincided with enhancer marks. Many of these genes were under NFIB control in both hair follicle stem cells and mammary alveolar epithelium. We propose that NFIB-STAT5 modules, possibly in conjunction with other transcription factors, control cell-specific genetic programs.

  1. Increased STAT3 phosphorylation on CD27(+) B-cells from common variable immunodeficiency disease patients.

    PubMed

    Clemente, Antonio; Pons, Jaume; Lanio, Nallibe; Cunill, Vanesa; Frontera, Guillem; Crespí, Catalina; Matamoros, Núria; Ferrer, Joana M

    2015-12-01

    Maturation and differentiation of B-cells are driven by T-cells' help through IL-21/STAT3 axis in GC centers or through extrafollicular pathways, in a T-independent manner. B-cell differentiation is defective in common variable immunodeficiency disease (CVID) patients. We investigated if IL-21/STAT3 axis alterations could influence B-cell fate. We activated purified CVID B-cells with surrogate T-dependent (anti-CD40), T-independent (TLR-9 ligand) stimuli or through B-cell receptor engagement (anti-IgM) with or without IL-21. IL-21 mediated STAT3 activation was greater on CD27(-) than CD27(+) B-cells depending on the stimulus. IL-21 alone induced STAT3 phosphorylation (pSTAT3) only on CD27(-) B-cells and IL-21 induced higher pSTAT3 levels on CD27(-) than CD27(+) B-cells after anti-IgM or anti-CD40 activation. CVID CD27(+) B-cells showed selective STAT3 hyperphosphorylation after activation with anti-IgM or anti-CD40 alone and anti-IgM, anti-CD40 or ODN combined with IL-21. Increased STAT3 activation during immune responses could result in B-cell differentiation defects in CVID.

  2. At High Levels, Constitutively Activated STAT3 Induces Apoptosis of Chronic Lymphocytic Leukemia Cells.

    PubMed

    Rozovski, Uri; Harris, David M; Li, Ping; Liu, Zhiming; Wu, Ji Yuan; Grgurevic, Srdana; Faderl, Stefan; Ferrajoli, Alessandra; Wierda, William G; Martinez, Matthew; Verstovsek, Srdan; Keating, Michael J; Estrov, Zeev

    2016-05-15

    In chronic lymphocytic leukemia (CLL), the increment in PBLs is slower than the expected increment calculated from the cells' proliferation rate, suggesting that cellular proliferation and apoptosis are concurrent. Exploring this phenomenon, we found overexpression of caspase-3, higher cleaved poly (ADP-ribose) polymerase levels (p < 0.007), and a higher apoptosis rate in cells from patients with high counts compared with cells from patients with low counts. Although we previously found that STAT3 protects CLL cells from apoptosis, STAT3 levels were significantly higher in cells from patients with high counts than in cells from patients with low counts. Furthermore, overexpression of STAT3 did not protect the cells. Rather, it upregulated caspase-3 and induced apoptosis. Remarkably, putative STAT3 binding sites were identified in the caspase-3 promoter, and a luciferase assay, chromatin immunoprecipitation, and an EMSA revealed that STAT3 activated caspase-3 However, caspase-3 levels increased only when STAT3 levels were sufficiently high. Using chromatin immunoprecipitation and EMSA, we found that STAT3 binds with low affinity to the caspase-3 promoter, suggesting that at high levels, STAT3 activates proapoptotic mechanisms and induces apoptosis in CLL cells.

  3. Differential roles of STAT3 in the initiation and growth of lung cancer.

    PubMed

    Zhou, J; Qu, Z; Yan, S; Sun, F; Whitsett, J A; Shapiro, S D; Xiao, G

    2015-07-01

    Signal transducer and activator of transcription 3 (STAT3) is linked to multiple cancers, including pulmonary adenocarcinoma. However, the role of STAT3 in lung cancer pathogenesis has not been determined. Using lung epithelial-specific inducible knockout strategies, we demonstrate that STAT3 has contrasting roles in the initiation and growth of both chemically and genetically induced lung cancers. Selective deletion of lung epithelial STAT3 in mice before cancer induction by the smoke carcinogen, urethane, resulted in increased lung tissue damage and inflammation, K-Ras oncogenic mutations and tumorigenesis. Deletion of lung epithelial STAT3 after establishment of lung cancer inhibited cancer cell proliferation. Simultaneous deletion of STAT3 and expression of oncogenic K-Ras in mouse lung elevated pulmonary injury, inflammation and tumorigenesis, but reduced tumor growth. These studies indicate that STAT3 prevents lung cancer initiation by maintaining pulmonary homeostasis under oncogenic stress, whereas it facilitates lung cancer progression by promoting cancer cell growth. These studies also provide a mechanistic basis for targeting STAT3 to lung cancer therapy.

  4. Coregulation of Genetic Programs by the Transcription Factors NFIB and STAT5

    PubMed Central

    Robinson, Gertraud W.; Kang, Keunsoo; Yoo, Kyung Hyun; Tang, Yong; Zhu, Bing-Mei; Yamaji, Daisuke; Colditz, Vera; Jang, Seung Jian; Gronostajski, Richard M.

    2014-01-01

    Mammary-specific genetic programs are activated during pregnancy by the common transcription factor signal transducer and activator of transcription (STAT) 5. More than one third of these genes carry nuclear factor I/B (NFIB) binding motifs that coincide with STAT5 in vivo binding, suggesting functional synergy between these two transcription factors. The role of NFIB in this governance was investigated in mice from which Nfib had been inactivated in mammary stem cells or in differentiating alveolar epithelium. Although NFIB was not required for alveolar expansion, the combined absence of NFIB and STAT5 prevented the formation of functional alveoli. NFIB controlled the expression of mammary-specific and STAT5-regulated genes and chromatin immunoprecipitation-sequencing established STAT5 and NFIB binding at composite regulatory elements containing histone H3 lysine dimethylation enhancer marks and progesterone receptor binding. By integrating previously published chromatin immunoprecipitation-sequencing data sets, the presence of NFIB-STAT5 modules in other cell types was investigated. Notably, genomic sites bound by NFIB in hair follicle stem cells were also occupied by STAT5 in mammary epithelium and coincided with enhancer marks. Many of these genes were under NFIB control in both hair follicle stem cells and mammary alveolar epithelium. We propose that NFIB-STAT5 modules, possibly in conjunction with other transcription factors, control cell-specific genetic programs. PMID:24678731

  5. Activation of Antitumorigenic Stat3beta in Breast Cancer by Splicing Redirection

    DTIC Science & Technology

    2013-07-01

    therapy. Nat Rev Cancer 2: 740-749. 3. Levy DE, Lee CK (2002) What does Stat3 do? J Clin Invest 109: 1143-1148. 4. Akira S ( 2000 ) Roles of STAT3 defined...breast cancer cells. Cancer Res 57: 978-987. 17. Inghirami G, Chiarle R, Simmons WJ, Piva R, Schlessinger K, et al. (2005) New and old functions of

  6. Role of Stat3 and ErbB2 in Breast Cancer

    DTIC Science & Technology

    2010-10-01

    Reportable Outcomes Papers published 1.--Geletu, M., Chaize, C., Arulanandam, R., Vultur, A., Kowolik, C., Anagnostopoulou, A., Jove , R. and Raptis...1. Yu,H., Pardoll,D., & Jove ,R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat. Rev. Cancer 9, 798-809 (2009). 2

  7. Role of STAT5b in Breast Cancer Progression and Metastasis

    DTIC Science & Technology

    2008-09-01

    J, Jove R: STATs in oncogenesis. Oncogene 2000, 19(21):2474- 2488. 3. Turkson J, Jove R: STAT proteins: novel molecular targets for cancer drug...Cell Physiol 2003, 197(2):157-168. 7. Haura EB, Turkson J, Jove R: Mechanisms of disease: Insights into the emerging role of signal transducers and

  8. Inhibition of Stat3 activation in the endometrium prevents implantation: a nonsteroidal approach to contraception.

    PubMed

    Catalano, Rob D; Johnson, Martin H; Campbell, Elizabeth A; Charnock-Jones, D Stephen; Smith, Stephen K; Sharkey, Andrew M

    2005-06-14

    Activation of the receptors for leukemia inhibitory factor (LIF) and IL-11 is essential for embryo attachment and decidualization in mice. Both receptors induce activation of the Stat family of signal transducers via the Jak/Stat pathway. Here, we aimed to establish whether activation of Stat3 in maternal endometrium is essential for successful implantation. Functional blockade of Stat3 before implantation, by injection into the uterine lumen of a cell-permeable Stat3 peptide inhibitor, reduced embryo implantation specifically by 70% (P < 0.001). Stat3 is phosphorylated in the luminal epithelium (LE) in response to LIF, and this phosphorylation was significantly reduced both in vitro and in vivo by the Stat3 inhibitor. The inhibitor also blocked induction by LIF of several LIF-regulated genes in the LE including Irg1, which has been shown previously to be essential for implantation. Successful implantation is therefore dependent on phosphorylation and activation of Stat3 in the endometrium before implantation. This finding provides a target for contraceptive development, based on selective blockade of signal transduction pathways essential for implantation. This study demonstrates that cell-permeable peptide inhibitors can be used effectively to target intracellular signaling pathways in the uterine LE.

  9. An Assessment Blueprint for EncStat: A Statistics Anxiety Intervention Program.

    ERIC Educational Resources Information Center

    Watson, Freda S.; Lang, Thomas R.; Kromrey, Jeffrey D.; Ferron, John M.; Hess, Melinda R.; Hogarty, Kristine Y.

    EncStat (Encouraged about Statistics) is a multimedia program being developed to identify and assist students with statistics anxiety or negative attitudes about statistics. This study explored the validity of the assessment instruments included in EncStat with respect to their diagnostic value for statistics anxiety and negative attitudes about…

  10. Brief Report: Screening Tool for Autism in Two-Year-Olds (STAT): Development and Preliminary Data.

    ERIC Educational Resources Information Center

    Stone, Wendy L.; Coonrod, Elaine E.; Ousley, Opal Y.

    2000-01-01

    A study examined the validity of the Screening Tool for Autism in Two-Year-Olds (STAT) as a stage 2 screening instrument in a clinic-based sample of two-year-olds with autism (n=12) and with nonautistic developmental disorders (n=21). Results provide preliminary support for the utility of the STAT as an early screening of autism. (Contains…

  11. Integrating Immunologic Signaling Networks: The JAK/STAT Pathway in Colitis and Colitis-Associated Cancer

    PubMed Central

    Zundler, Sebastian; Neurath, Markus F.

    2016-01-01

    Cytokines are believed to be crucial mediators of chronic intestinal inflammation in inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC). Many of these cytokines trigger cellular effects and functions through signaling via janus kinase (JAK) and signal transducer and activator of transcription (STAT) molecules. In this way, JAK/STAT signaling controls important events like cell differentiation, secretion of cytokines or proliferation and apoptosis in IBD in both adaptive and innate immune cells. Moreover, JAK/STAT signaling, especially via the IL-6/STAT3 axis, is believed to be involved in the transition of inflammatory lesions to tumors leading to colitis-associated cancer (CAC). In this review, we will introduce the main cellular players and cytokines that contribute to pathogenesis of IBD by JAK/STAT signaling, and will highlight the integrative function that JAK/STATs exert in this context as well as their divergent role in different cells and processes. Moreover, we will explain current concepts of the implication of JAK/STAT signaling in CAC and finally discuss present and future therapies for IBD that interfere with JAK/STAT signaling. PMID:26938566

  12. Teaching an Introductory Statistics Course with CyberStats, an Electronic Textbook

    ERIC Educational Resources Information Center

    Symanzik, Jurgen; Vukasinovic, Natascha

    2006-01-01

    In the Fall 2001 semester, we taught a "Web-enhanced" version of the undergraduate course "Statistical Methods" ("STAT 2000") at Utah State University. The course used the electronic textbook CyberStats in addition to "face-to-face" teaching. This paper gives insight in our experiences in teaching this…

  13. Signal transducer and activator of transcription 5B (STAT5B) modulates adipocyte differentiation via MOF.

    PubMed

    Gao, Peng; Zhang, Yuchao; Liu, Yuantao; Chen, Jicui; Zong, Chen; Yu, Cong; Cui, Shang; Gao, Weina; Qin, Dandan; Sun, Wenchuan; Li, Xia; Wang, Xiangdong

    2015-12-01

    The role and mechanism of signal transducer and activator of transcription 5B (STAT5B) in adipogenesis remain unclear. In this study, our data showed that Males absent on the first (MOF) protein expression was increased during 3 T3-L1 preadipocytes differentiation accompanied with STAT5B expression increasing. Over-expression STAT5B enhanced MOF promoter trans-activation in HeLa cells. Mutagenesis assay and ChIP analysis exhibited that STAT5B was able to bind MOF promoter. Knocking-down STAT5B in 3 T3-L1 preadipocytes led to decreased expression of MOF, but resulted in increased expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid-binding protein 4 (Fabp4), which were important factors or enzymes for adipogenesis. We also found that knocking-down MOF in 3 T3-L1 preadipocytes resulted in increased expression of PPARγ, C/EBPα and Fabp4, which was in the same trend as STAT5B knocking-down. Over-expression MOF resulted in reduced promoter trans-activation activity of C/EBPα. These results suggest that STAT5B and MOF work as negative regulators in adipogenesis, and STAT5B modulates preadipocytes differentiation partially by regulating MOF expression.

  14. Stat3/Cdc25a-dependent cell proliferation promotes embryonic axis extension during zebrafish gastrulation

    PubMed Central

    Sepich, Diane S.

    2017-01-01

    Cell proliferation has generally been considered dispensable for anteroposterior extension of embryonic axis during vertebrate gastrulation. Signal transducer and activator of transcription 3 (Stat3), a conserved controller of cell proliferation, survival and regeneration, is associated with human scoliosis, cancer and Hyper IgE Syndrome. Zebrafish Stat3 was proposed to govern convergence and extension gastrulation movements in part by promoting Wnt/Planar Cell Polarity (PCP) signaling, a conserved regulator of mediolaterally polarized cell behaviors. Here, using zebrafish stat3 null mutants and pharmacological tools, we demonstrate that cell proliferation contributes to anteroposterior embryonic axis extension. Zebrafish embryos lacking maternal and zygotic Stat3 expression exhibit normal convergence movements and planar cell polarity signaling, but transient axis elongation defect due to insufficient number of cells resulting largely from reduced cell proliferation and increased apoptosis. Pharmacologic inhibition of cell proliferation during gastrulation phenocopied axis elongation defects. Stat3 regulates cell proliferation and axis extension in part via upregulation of Cdc25a expression during oogenesis. Accordingly, restoring Cdc25a expression in stat3 mutants partially suppressed cell proliferation and gastrulation defects. During later development, stat3 mutant zebrafish exhibit stunted growth, scoliosis, excessive inflammation, and fail to thrive, affording a genetic tool to study Stat3 function in vertebrate development, regeneration, and disease. PMID:28222105

  15. Activated STAT1 transcription factors conduct distinct saltatory movements in the cell nucleus.

    PubMed

    Speil, Jasmin; Baumgart, Eugen; Siebrasse, Jan-Peter; Veith, Roman; Vinkemeier, Uwe; Kubitscheck, Ulrich

    2011-12-07

    The activation of STAT transcription factors is a critical determinant of their subcellular distribution and their ability to regulate gene expression. Yet, it is not known how activation affects the behavior of individual STAT molecules in the cytoplasm and nucleus. To investigate this issue, we injected fluorescently labeled STAT1 in living HeLa cells and traced them by single-molecule microscopy. We determined that STAT1 moved stochastically in the cytoplasm and nucleus with very short residence times (<0.03 s) before activation. Upon activation, STAT1 mobility in the cytoplasm decreased ∼2.5-fold, indicating reduced movement of STAT1/importinα/β complexes to the nucleus. In the nucleus, activated STAT1 displayed a distinct saltatory mobility, with residence times of up to 5 s and intermittent diffusive motion. In this manner, activated STAT1 factors can occupy their putative chromatin target sites within ∼2 s. These results provide a better understanding of the timescales on which cellular signaling and regulated gene transcription operate at the single-molecule level.

  16. Chemical and Hormonal Effects on STAT5b-Dependent Sexual Dimorphism of the Liver Transcriptome.

    EPA Science Inventory

    The growth hormone (GH)-activated transcription factor signal transducer and activator of transcription 5b (STAT5b) is a key regulator of sexually dimorphic gene expression in the liver. Suppression of hepatic STAT5b signaling is associated with lipid metabolic dysfunction leadi...

  17. Stat3 promotes mitochondrial transcription and oxidative respiration during maintenance and induction of naive pluripotency.

    PubMed

    Carbognin, Elena; Betto, Riccardo M; Soriano, Maria E; Smith, Austin G; Martello, Graziano

    2016-03-15

    Transcription factor Stat3 directs self-renewal of pluripotent mouse embryonic stem (ES) cells downstream of the cytokine leukemia inhibitory factor (LIF). Stat3 upregulates pivotal transcription factors in the ES cell gene regulatory network to sustain naïve identity. Stat3 also contributes to the rapid proliferation of ES cells. Here, we show that Stat3 increases the expression of mitochondrial-encoded transcripts and enhances oxidative metabolism. Chromatin immunoprecipitation reveals that Stat3 binds to the mitochondrial genome, consistent with direct transcriptional regulation. An engineered form of Stat3 that localizes predominantly to mitochondria is sufficient to support enhanced proliferation of ES cells, but not to maintain their undifferentiated phenotype. Furthermore, during reprogramming from primed to naïve states of pluripotency, Stat3 similarly upregulates mitochondrial transcripts and facilitates metabolic resetting. These findings suggest that the potent stimulation of naïve pluripotency by LIF/Stat3 is attributable to parallel and synergistic induction of both mitochondrial respiration and nuclear transcription factors.

  18. TRIM8 regulates stemness in glioblastoma through PIAS3-STAT3.

    PubMed

    Zhang, Changming; Mukherjee, Subhas; Tucker-Burden, Carol; Ross, James L; Chau, Monica J; Kong, Jun; Brat, Daniel J

    2017-03-01

    Glioblastoma (GBM) is the most malignant form of primary brain tumor, and GBM stem-like cells (GSCs) contribute to the rapid growth, therapeutic resistance, and clinical recurrence of these fatal tumors. STAT3 signaling supports the maintenance and proliferation of GSCs, yet regulatory mechanisms are not completely understood. Here, we report that tri-partite motif-containing protein 8 (TRIM8) activates STAT3 signaling to maintain stemness and self-renewing capabilities of GSCs. TRIM8 (also known as 'glioblastoma-expressed ring finger protein') is expressed equally in GBM and normal brain tissues, despite its hemizygous deletion in the large majority of GBMs, and its expression is highly correlated with stem cell markers. Experimental knockdown of TRIM8 reduced GSC self-renewal and expression of SOX2, NESTIN, and p-STAT3, and promoted glial differentiation. Overexpression of TRIM8 led to higher expression of p-STAT3, c-MYC, SOX2, NESTIN, and CD133, and enhanced GSC self-renewal. We found that TRIM8 activates STAT3 by suppressing the expression of PIAS3, an inhibitor of STAT3, most likely through E3-mediated ubiquitination and proteasomal degradation. Interestingly, we also found that STAT3 activation upregulates TRIM8, providing a mechanism for normalized TRIM8 expression in the setting of hemizygous gene deletion. These data demonstrate that bidirectional TRIM8-STAT3 signaling regulates stemness in GSC.

  19. Spirit Movie of Phobos Eclipse, Sol 675

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Spirit Phobos Eclipse Animation

    NASA's Mars Exploration Rover Spirit observed the Martian moon Phobos entering the shadow of Mars during the night of the rover's 675th sol (Nov. 27, 2005). The panoramic camera captured 16 images, spaced 10 seconds apart, covering the period from when Phobos was in full sunlight to when it was entirely in shadow. As with our own Moon during lunar eclipses on Earth, even when in the planet's shadow, Phobos was not entirely dark. The small amount of light still visible from Phobos is a kind of 'Mars-shine' -- sunlight reflected through Mars' atmosphere and into the shadowed region.

    This clip is a sequence of the 16 images showing the eclipse at about 10 times normal speed. It shows the movement of Phobos from left to right as the moon enters the shadow. Scientists are using information about the precise timing of Martian moon eclipses gained from observations such as these to refine calculations about the orbital path of Phobos. The precise position of Phobos will be important to any future spacecraft taking detailed pictures of the moon or landing on its surface.

  20. Sol-gel entrapped cobalt complex

    SciTech Connect

    Lima, Omar J. de; Papacidero, Andrea T.; Rocha, Lucas A.; Sacco, Herica C.; Nassar, Eduardo J.; Ciuffi, Katia J.; Bueno, Luciano A.; Messaddeq, Younes; Ribeiro, Sidney J.L

    2003-03-15

    This work describes optimized conditions for preparation of a cobalt complex entrapped in alumina amorphous materials in the form of powder. The hybrid materials, CoNHG, were obtained by a nonhydrolytic sol-gel route through condensation of aluminum chloride with diisopropylether in the presence of cobalt chloride. The materials were calcined at various temperatures. The presence of cobalt entrapped in the alumina matrix is confirmed by ultraviolet visible spectroscopy. The materials have been characterized by X-ray diffraction (XRD), surface area analysis, thermogravimetric analysis (TGA), differential thermal analyses (DTA) and transmission electron microscopy (TEM). The prepared alumina matrix materials are amorphous, even after heat treatment up to 750 deg. C. The XRD, TGA/DTA and TEM data support the increase of sample crystallization with increasing temperature. The specific surface area, pore size and pore diameter changed as a function of the heat treatment temperature employed. Different heat treatment temperatures result in materials with different compositions and structures, and influence their catalytic activity. The entrapped cobalt materials calcined at 750 deg. C efficiently catalyzed the epoxidation of (Z)-cyclooctene using iodozylbenzene as the oxygen donor.

  1. Sol Duc Hot Springs feasibility study

    SciTech Connect

    Not Available

    1981-12-01

    Sol Duc Springs is located in the Olympic National Park in western Washington state. Since the turn of the century, the area has served as a resort, offering hot mineral baths, lodge and overnight cabin accommodations. The Park Service, in conjunction with the concessionaire, is in the process of renovating the existing facilities, most of which are approximately 50 years old. The present renovation work consists of removing all of the existing cabins and replacing them with 36 new units. In addition, a new hot pool is planned to replace the existing one. This report explores the possibility of a more efficient use of the geothermal resource to accompany other planned improvements. It is important to note that the system outlined is based upon the resource development as it exists currently. That is, the geothermal source is considered to be: the two existing wells and the hot springs currently in use. In addition, every effort has been made to accommodate the priorities for utilization as set forth by the Park Service.

  2. Electrophoretic Porosimetry of Sol-Gels

    NASA Technical Reports Server (NTRS)

    Snow, L. A.; Smith, D. D.; Sibille, L.; Hunt, A. J.; Ng, J.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    It has been hypothesized that gravity has an effect on the formation and resulting microstructure of sol-gels. In order to more clearly resolve the effect of gravity, pores may be non-destructively analyzed in the wet gel, circumventing the shrinkage and coarsening associated with the drying procedure. We discuss the development of an electrophoretic technique, analogous to affinity chromatography, for the determination of pore size distribution and its application to silica gels. Specifically a monodisperse charged dye is monitored by an optical densitometer as it moves through the wet gel under the influence of an electric field. The transmittance data (output) represents the convolution of the dye concentration profile at the beginning of the run (input) with the pore size distribution (transfer function), i.e. linear systems theory applies. Because of the practical difficulty in producing a delta function input dye profile we prefer instead to use a step function. Average pore size is then related to the velocity of this dye front, while the pore size distribution is related to the spreading of the front. Preliminary results of this electrophoretic porosimetry and its application to ground and space-grown samples will be discussed.

  3. The Inflammatory Transcription Factors NFκB, STAT1 and STAT3 Drive Age-Associated Transcriptional Changes in the Human Kidney.

    PubMed

    O'Brown, Zach K; Van Nostrand, Eric L; Higgins, John P; Kim, Stuart K

    2015-12-01

    Human kidney function declines with age, accompanied by stereotyped changes in gene expression and histopathology, but the mechanisms underlying these changes are largely unknown. To identify potential regulators of kidney aging, we compared age-associated transcriptional changes in the human kidney with genome-wide maps of transcription factor occupancy from ChIP-seq datasets in human cells. The strongest candidates were the inflammation-associated transcription factors NFκB, STAT1 and STAT3, the activities of which increase with age in epithelial compartments of the renal cortex. Stimulation of renal tubular epithelial cells with the inflammatory cytokines IL-6 (a STAT3 activator), IFNγ (a STAT1 activator), or TNFα (an NFκB activator) recapitulated age-associated gene expression changes. We show that common DNA variants in RELA and NFKB1, the two genes encoding subunits of the NFκB transcription factor, associate with kidney function and chronic kidney disease in gene association studies, providing the first evidence that genetic variation in NFκB contributes to renal aging phenotypes. Our results suggest that NFκB, STAT1 and STAT3 underlie transcriptional changes and chronic inflammation in the aging human kidney.

  4. La Piedad Michoacán Mexico Virus V protein antagonizes type I interferon response by binding STAT2 protein and preventing STATs nuclear translocation.

    PubMed

    Pisanelli, Giuseppe; Laurent-Rolle, Maudry; Manicassamy, Balaji; Belicha-Villanueva, Alan; Morrison, Juliet; Lozano-Dubernard, Bernardo; Castro-Peralta, Felipa; Iovane, Giuseppe; García-Sastre, Adolfo

    2016-02-02

    La Piedad Michoacán Mexico Virus (LPMV) is a member of the Rubulavirus genus within the Paramyxoviridae family. LPMV is the etiologic agent of "blue eye disease", causing a significant disease burden in swine in Mexico with long-term implications for the agricultural industry. This virus mainly affects piglets and is characterized by meningoencephalitis and respiratory distress. It also affects adult pigs, causing reduced fertility and abortions in females, and orchitis and epididymitis in males. Viruses of the Paramyxoviridae family evade the innate immune response by targeting components of the interferon (IFN) signaling pathway. The V protein, expressed by most paramyxoviruses, is a well-characterized IFN signaling antagonist. Until now, there were no reports on the role of the LPMV-V protein in inhibiting the IFN response. In this study we demonstrate that LPMV-V protein antagonizes type I but not type II IFN signaling by binding STAT2, a component of the type I IFN cascade. Our results indicate that the last 18 amino acids of LPMV-V protein are required for binding to STAT2 in human and swine cells. While LPMV-V protein does not affect the protein levels of STAT1 or STAT2, it does prevent the IFN-induced phosphorylation and nuclear translocation of STAT1 and STAT2 thereby inhibiting cellular responses to IFN α/β.

  5. Mitochondrial STAT3 and reactive oxygen species: A fulcrum of adipogenesis?

    PubMed Central

    Kramer, Adam H; Kadye, Rose; Houseman, Pascalene S; Prinsloo, Earl

    2015-01-01

    The balance between cellular lineages can be controlled by reactive oxygen species (ROS). Cellular differentiation into adipocytes is highly dependent on the production of ROS to initiate the process through activation of multiple interlinked factors that stimulate mitotic clonal expansion and cellular maturation. The signal transducer and activator of transcription family of signaling proteins have accepted roles in adipogenesis and associated lipogenesis. Non-canonical mitochondrial localization of STAT3 and other members of the STAT family however opens up new avenues for investigation of its role in the aforementioned processes. Following recent observations of differences in mitochondrially localized serine 727 phosphorylated STAT3 (mtSTAT3-pS727) in preadipocytes and adipocytes, here, we hypothesize and speculate further on the role of mitochondrial STAT3 in adipogenesis. PMID:27127727

  6. Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and migration

    SciTech Connect

    Arulanandam, Rozanne; Geletu, Mulu; Feracci, Helene; Raptis, Leda

    2010-03-10

    Rac1 (Rac) is a member of the Rho family of small GTPases which controls cell migration by regulating the organization of actin filaments. Previous results suggested that mutationally activated forms of the Rho GTPases can activate the Signal Transducer and Activator of Transcription-3 (Stat3), but the exact mechanism is a matter of controversy. We recently demonstrated that Stat3 activity of cultured cells increases dramatically following E-cadherin engagement. To better understand this pathway, we now compared Stat3 activity levels in mouse HC11 cells before and after expression of the mutationally activated Rac1 (Rac{sup V12}), at different cell densities. The results revealed for the first time a dramatic increase in protein levels and activity of both the endogenous Rac and Rac{sup V12} with cell density, which was due to inhibition of proteasomal degradation. In addition, Rac{sup V12}-expressing cells had higher Stat3, tyrosine-705 phosphorylation and activity levels at all densities, indicating that Rac{sup V12} is able to activate Stat3. Further examination of the mechanism of Stat3 activation showed that Rac{sup V12} expression caused a surge in mRNA of Interleukin-6 (IL6) family cytokines, known potent Stat3 activators. Knockdown of gp130, the common subunit of this family reduced Stat3 activity, indicating that these cytokines may be responsible for the Stat3 activation by Rac{sup V12}. The upregulation of IL6 family cytokines was required for cell migration and proliferation induced by Rac{sup V12}, as shown by gp130 knockdown experiments, thus demonstrating that the gp130/Stat3 axis represents an essential effector of activated Rac for the regulation of key cellular functions.

  7. MicroRNA-124 suppresses growth of human hepatocellular carcinoma by targeting STAT3

    SciTech Connect

    Lu, Yanxin; Yue, Xupeng; Cui, Yuanyuan; Zhang, Jufeng; Wang, KeWei

    2013-11-29

    Highlights: •miR-124 is down-regulated in hepatocellular carcinoma HepG2 cells. •Over-expression of miR-124 suppresses proliferation and induces apoptosis in HepG2 cells. •miR-124 inhibits xenograft tumor growth in nude mice implanted with HepG2 cells by reducing STAT3 expression. •STATs function as a novel target of miR-124 in HCC HepG2 cells. -- Abstract: The aberrant expression of microRNAs is associated with development and progression of cancers. Down-regulation of miR-124 has been demonstrated in the hepatocellular carcinoma (HCC), but the underlying mechanism by which miR-124 suppresses tumorigenesis in HCC remains elusive. In this study, we found that miR-124 suppresses the tumor growth of HCC through targeting the signal transducers and activators of transcription 3 (STAT3). Overexpression of miR-124 suppressed proliferation and induced apoptosis in HepG-2 cells. Luciferase assay confirmed that miR-124 binding to the 3′-UTR region of STAT3 inhibited the expression of STAT3 and phosphorylated STAT3 proteins in HepG-2 cells. Knockdown of STAT3 by siRNA in HepG-2 cells mimicked the effect induced by miR-124. Overexpression of STAT3 in miR-124-transfected HepG-2 cells effectively rescued the inhibition of cell proliferation caused by miR-124. Furthermore, miR-124 suppressed xenograft tumor growth in nude mice implanted with HepG-2 cells by reducing STAT3 expression. Taken together, our findings show that miR-124 functions as tumor suppressor in HCC by targeting STAT3, and miR-124 may therefore serve as a biomarker for diagnosis and therapeutics in HCC.

  8. Nongenomic STAT5-dependent effects on Golgi apparatus and endoplasmic reticulum structure and function.

    PubMed

    Lee, Jason E; Yang, Yang-Ming; Liang, Feng-Xia; Gough, Daniel J; Levy, David E; Sehgal, Pravin B

    2012-03-01

    We report unexpected nongenomic functions of signal transducer and activator of transcription (STAT) 5 species in the cytoplasm aimed at preserving the structure and function of the Golgi apparatus and rough endoplasmic reticulum (ER) in vascular cells. Immunoimaging and green fluorescent protein-tagged-STAT5a protein localization studies showed the constitutive association of nonphosphorylated STAT5a, and to a lesser extent STAT5b, with the Golgi apparatus and of STAT5a with centrosomes in human pulmonary arterial endothelial and smooth muscle cells. Acute knockdown of STAT5a/b species using small interfering RNAs (siRNAs), including in the presence of an mRNA synthesis inhibitor (5,6-dichloro-1-β-d-ribofuranosylbenzimidazole), produced a dramatic phenotype within 1 day, consisting of dilatation and fragmentation of Golgi cisternae, a marked tubule-to-cyst change in the ER, increased accumulation of reticulon-4 (RTN4)/Nogo-B and atlastin-3 (ATL3) at cyst-zone boundaries, cystic separation of the outer and inner nuclear membranes, accompanied by scalloped/lunate distortion of the nucleus, with accumulation of RTN4 on convex sides of distorted nuclei. These cells showed inhibition of vesicular stomatitis virus G protein glycoprotein trafficking, mitochondrial fragmentation, and reduced mitochondrial function. STAT5a/b(-/-) mouse embryo fibroblasts also showed altered ER/Golgi dynamics. RTN4 knockdown using siRNA did not affect development of the cystic phenotype; ATL3 siRNA led to effacement of cyst-zone boundaries. In magnetic-bead cross-immunopanning assays, ATL3 bound both STAT5a and STAT5b. Remarkably, this novel cystic ER/lunate nucleus phenotype was characteristic of vascular cells in arterial lesions of idiopathic pulmonary hypertension, an unrelentingly fatal human disease. These data provide evidence of a STAT-family protein regulating the structure of a cytoplasmic organelle and implicate this mechanism in the pathogenesis of a human disease.

  9. [The analysis of threshold effect using Empower Stats software].

    PubMed

    Lin, Lin; Chen, Chang-zhong; Yu, Xiao-dan

    2013-11-01

    In many studies about biomedical research factors influence on the outcome variable, it has no influence or has a positive effect within a certain range. Exceeding a certain threshold value, the size of the effect and/or orientation will change, which called threshold effect. Whether there are threshold effects in the analysis of factors (x) on the outcome variable (y), it can be observed through a smooth curve fitting to see whether there is a piecewise linear relationship. And then using segmented regression model, LRT test and Bootstrap resampling method to analyze the threshold effect. Empower Stats software developed by American X & Y Solutions Inc has a threshold effect analysis module. You can input the threshold value at a given threshold segmentation simulated data. You may not input the threshold, but determined the optimal threshold analog data by the software automatically, and calculated the threshold confidence intervals.

  10. StatCast Dashboard: Exploration of Spatiotemporal Baseball Data.

    PubMed

    Lage, Marcos; Ono, Jorge Piazentin; Cervone, Daniel; Chiang, Justin; Dietrich, Carlos; Silva, Claudio T

    2016-01-01

    Major League Baseball (MLB) has a long history of providing detailed, high-quality data, leading to a tremendous surge in sports analytics research in recent years. In 2015, MLB.com released the StatCast spatiotemporal data-tracking system, which has been used in approximately 2,500 games since its inception to capture player and ball locations as well as semantically meaningful game events. This article presents a visualization and analytics infrastructure to help query and facilitate the analysis of this new tracking data. The goal is to go beyond descriptive statistics of individual plays, allowing analysts to study diverse collections of games and game events. The proposed system enables the exploration of the data using a simple querying interface and a set of flexible interactive visualization tools.

  11. Slow Release of Plant Volatiles Using Sol-Gel Dispensers.

    PubMed

    Bian, L; Sun, X L; Cai, X M; Chen, Z M

    2014-12-01

    The black citrus aphid, also known as the tea aphid, (Toxoptera aurantii Boyer) attacks economically important crops, including tea (Camellia sinensis (L.) O. Kuntze). In the current study, silica sol-gel formulations were screened to find one that could carry and release C. sinensis plant volatiles to lure black citrus aphids in a greenhouse. The common plant volatile trans-2-hexen-1-al was used as a model molecule to screen for suitable sol-gel formulations. A zNose (Electronic Sensor Technology, Newbury Park, CA) transportable gas chromatograph was used to continuously monitor the volatile emissions. A sol-gel formulation containing tetramethyl orthosilicate and methyltrimethoxysilane in an 8:2 (vol:vol) ratio was selected to develop a slow-release dispenser. The half-life of trans-2-hexen-1-al in the sol-gel dispenser increased slightly with the volume of this compound in the dispenser. Ten different volatiles were tested in the sol-gel dispenser. Alcohols of 6-10 carbons had the longest half-lives (3.01-3.77 d), while esters of 6-12 carbons had the shortest (1.53-2.28 d). Release of these volatiles from the dispensers could not be detected by the zNose after 16 d (cis-3-hexenyl acetate) to 26 d (3,7-dimethylocta-1,6-dien-3-ol). In greenhouse experiments, trans-2-hexen-1-al and cis-3-hexen-1-ol released from the sol-gel dispensers attracted aphids for ≍17 d, and release of these volatiles could not be detected by the zNose after ≍24 d. The sol-gel dispensers performed adequately for the slow release of plant volatiles to trap aphids in the greenhouse.

  12. Sol-gel encapsulation for controlled drug release and biosensing

    NASA Astrophysics Data System (ADS)

    Fang, Jonathan

    The main focus of this dissertation is to investigate the use of sol-gel encapsulation of biomolecules for controlled drug release and biosensing. Controlled drug release has advantages over conventional therapies in that it maintains a constant, therapeutic drug level in the body for prolonged periods of time. The anti-hypertensive drug Captopril was encapsulated in sol-gel materials of various forms, such as silica xerogels and nanoparticles. The primary objective was to show that sol-gel silica materials are promising drug carriers for controlled release by releasing Captopril at a release rate that is within a therapeutic range. We were able to demonstrate desired release for over a week from Captopril-doped silica xerogels and overall release from Captopril-doped silica nanoparticles. As an aside, the antibiotic Vancomycin was also encapsulated in these porous silica nanoparticles and desired release was obtained for several days in-vitro. The second part of the dissertation focuses on immobilizing antibodies and proteins in sol-gel to detect various analytes, such as hormones and amino acids. Sol-gel competitive immunoassays on antibody-doped silica xerogels were used for hormone detection. Calibration for insulin and C-peptide in standard solutions was obtained in the nM range. In addition, NASA-Ames is also interested in developing a reagentless biosensor using bacterial periplasmic binding proteins (bPBPs) to detect specific biomarkers, such as amino acids and phosphate. These bPBPs were doubly labeled with two different fluorophores and encapsulated in silica xerogels. Ligand-binding experiments were performed on the bPBPs in solution and in sol-gel. Ligand-binding was monitored by fluorescence resonance energy transfer (FRET) between the two fluorophores on the bPBP. Titration data show that one bPBP has retained its ligand-binding properties in sol-gel.

  13. ERp57 modulates STAT3 activity in radioresistant laryngeal cancer cells and serves as a prognostic marker for laryngeal cancer.

    PubMed

    Choe, Min Ho; Min, Joong Won; Jeon, Hong Bae; Cho, Dong-Hyung; Oh, Jeong Su; Lee, Hyun Gyu; Hwang, Sang-Gu; An, Sungkwan; Han, Young-Hoon; Kim, Jae-Sung

    2015-02-20

    Although targeting radioresistant tumor cells is essential for enhancing the efficacy of radiotherapy, the signals activated in resistant tumors are still unclear. This study shows that ERp57 contributes to radioresistance of laryngeal cancer by activating STAT3. Increased ERp57 was associated with the radioresistant phenotype of laryngeal cancer cells. Interestingly, increased interaction between ERp57 and STAT3 was observed in radioresistant cells, compared to the control cells. This physical complex is required for the activation of STAT3 in the radioresistant cells. Among STAT3-regulatory genes, Mcl-1 was predominantly regulated by ERp57. Inhibition of STAT3 activity with a chemical inhibitor or siRNA-mediated depletion of Mcl-1 sensitized radioresistant cells to irradiation, suggesting that the ERp57-STAT3-Mcl-1 axis regulates radioresistance of laryngeal cancer cells. Furthermore, we observed a positive correlation between ERp57 and phosphorylated STAT3 or Mcl-1 and in vivo interactions between ERp57 and STAT3 in human laryngeal cancer. Importantly, we also found that increased ERp57-STAT3 complex was associated with poor prognosis in human laryngeal cancer, indicating the prognostic role of ERp57-STAT3 regulation. Overall, our data suggest that ERp57-STAT3 regulation functions in radioresistance of laryngeal cancer, and targeting the ERp57-STAT3 pathway might be important for enhancing the efficacy of radiotherapy in human laryngeal cancer.

  14. Molecular cloning and expression analysis of signal transducer and activator of transcription (STAT) from the Chinese white shrimp Fenneropenaeus chinensis.

    PubMed

    Sun, Chen; Shao, Hong-Lian; Zhang, Xiao-Wen; Zhao, Xiao-Fan; Wang, Jin-Xing

    2011-11-01

    Innate immunity is the first line of defense by a host against invading pathogens. Several signaling pathways participate in the immune response, one of which is the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. Various evidences have been provided to suggest that the JAK/STAT pathway is involved in both antibacterial and antiviral immunities. In this study, the full-length cDNA and gene sequence of STAT (designated as FcSTAT) was cloned from the Chinese white shrimp, Fenneropenaeus chinensis. Phylogenetic analysis reveals that the FcSTAT is clustered with STAT5s and STAT6s from vertebrates and STATs from invertebrates. Quantitative real-time PCR exhibited that the FcSTAT had a wide distribution in all detected tissues and developmental stages. Time course analysis of the transcription level after WSSV challenge showed a noticeably early up-regulation of FcSTAT in hemocytes, hepatopancreas, and intestines. The expression levels of FcSTAT increased corresponding to Vibrio anguillarum stimulation in both hemocytes and hepatopancreas as well. All these imply that the JAK/STAT pathway participates in the immune response against bacteria and virus in F. chinensis.

  15. Phosphorylated STAT5 regulates p53 expression via BRCA1/BARD1-NPM1 and MDM2

    PubMed Central

    Ren, Zhuo; Aerts, Joeri L; Vandenplas, Hugo; Wang, Jiance A; Gorbenko, Olena; Chen, Jack P; Giron, Philippe; Heirman, Carlo; Goyvaerts, Cleo; Zacksenhaus, Eldad; Minden, Mark D; Stambolic, Vuk; Breckpot, Karine; De Grève, Jacques

    2016-01-01

    Signal transducer and activator of transcription 5 (STAT5) and nucleophosmin (NPM1) are critical regulators of multiple biological and pathological processes. Although a reciprocal regulatory relationship was established between STAT5A and a NPM–ALK fusion protein in T-cell lymphoma, no direct connection between STAT5 and wild-type NPM1 has been documented. Here we demonstrate a mutually regulatory relationship between STAT5 and NPM1. Induction of STAT5 phosphorylation at Y694 (P-STAT5) diminished NPM1 expression, whereas inhibition of STAT5 phosphorylation enhanced NPM1 expression. Conversely, NPM1 not only negatively regulated STAT5 phosphorylation but also preserved unphosphorylated STAT5 level. Mechanistically, we show that NPM1 downregulation by P-STAT5 is mediated by impairing the BRCA1-BARD1 ubiquitin ligase, which controls the stability of NPM1. In turn, decreased NPM1 levels led to suppression of p53 expression, resulting in enhanced cell survival. This study reveals a new STAT5 signaling pathway regulating p53 expression via NPM1 and uncovers new therapeutic targets for anticancer treatment in tumors driven by STAT5 signaling. PMID:28005077

  16. Phosphorylated STAT5 regulates p53 expression via BRCA1/BARD1-NPM1 and MDM2.

    PubMed

    Ren, Zhuo; Aerts, Joeri L; Vandenplas, Hugo; Wang, Jiance A; Gorbenko, Olena; Chen, Jack P; Giron, Philippe; Heirman, Carlo; Goyvaerts, Cleo; Zacksenhaus, Eldad; Minden, Mark D; Stambolic, Vuk; Breckpot, Karine; De Grève, Jacques

    2016-12-22

    Signal transducer and activator of transcription 5 (STAT5) and nucleophosmin (NPM1) are critical regulators of multiple biological and pathological processes. Although a reciprocal regulatory relationship was established between STAT5A and a NPM-ALK fusion protein in T-cell lymphoma, no direct connection between STAT5 and wild-type NPM1 has been documented. Here we demonstrate a mutually regulatory relationship between STAT5 and NPM1. Induction of STAT5 phosphorylation at Y694 (P-STAT5) diminished NPM1 expression, whereas inhibition of STAT5 phosphorylation enhanced NPM1 expression. Conversely, NPM1 not only negatively regulated STAT5 phosphorylation but also preserved unphosphorylated STAT5 level. Mechanistically, we show that NPM1 downregulation by P-STAT5 is mediated by impairing the BRCA1-BARD1 ubiquitin ligase, which controls the stability of NPM1. In turn, decreased NPM1 levels led to suppression of p53 expression, resulting in enhanced cell survival. This study reveals a new STAT5 signaling pathway regulating p53 expression via NPM1 and uncovers new therapeutic targets for anticancer treatment in tumors driven by STAT5 signaling.

  17. The Sol project: the sun in time

    NASA Astrophysics Data System (ADS)

    Pinho, L. G. F.; Porto de Mello, G. F.; de Medeiros, J. R.; Do Nascimento, J. D., Jr.; da Silva, L.

    2003-08-01

    The solar place in the set of stellar properties of the neighborhood, such as chemical composition, magnetic activity, lithium depletion, and others, suggests that the Sun may not exactly be a representative star. A few of the solar putative peculiarities seem to involve details of its evolutionary history, and that some light might be shed onto this question by a new approach based on the analysis of a time line in the HR diagram, searching for stars that might represent past, present and future solar evolutionary loci. The SOL Project (Solar Origin and Life) aims towards the identification, among the nearby stars, of those that share in detail the solar evolutionary track, in order to put the Sun as a star in proper perspective. We aim at obtaining, spectroscopically, atmospheric parameters, Fe and Li abundances, space velocities, state of evolution, degree of chromospheric activity and rotational velocities of a stellar sample, selected from precise astrometry and photometry of the Hipparcos catalogue, as to represent the Sun in various evolutionary stages along the solar mass, solar metallicity theoretical track: the early Sun, the present Sun, the subgiant Sun and the giant Sun. Here we present a progress report of the survey: the sample selection, OPD spectroscopic observations and preliminary results of the atmospheric parameters and evolutionary status analysis. As a by-product, we also present a new effective temperature calibration, based on published Infrared Flux Method data, and calibrated explicitly for precise spectroscopic stellar metallicities, for the (B-V), (BT-VT), (R-I), (V-I), (V-R) and (V-K) color indices, and valid for cool, normal and moderately metal-poor giant stars.

  18. Clinicopathological significance of STAT4 in hepatocellular carcinoma and its effect on cell growth and apoptosis

    PubMed Central

    Li, Jianjun; Liang, Lu; Liu, Yongru; Luo, Yihuan; Liang, Xiaona; Luo, Dianzhong; Feng, Zhenbo; Dang, Yiwu; Yang, Lihua; Chen, Gang

    2016-01-01

    Background Recent studies showed that signal transducer and activator of transcription 4 (STAT4) was downregulated in hepatocellular carcinoma (HCC) tissues. However, the role of STAT4 in HCC is still unknown. The aim of this study is to explore the association between STAT4 expression and other clinicopathological features in HCC and to test the effect of STAT4 on cell growth and apoptosis in vitro. Methods STAT4 was evaluated by immunohistochemistry in 171 HCC and corresponding paraneoplastic liver, 37 cirrhosis, and 33 normal liver tissues. Association between STAT4 and clinicopathological parameters was analyzed. Meta-analysis on STAT4 in cancer was performed. The effect of STAT4 small interfering RNA (siRNA) on cell growth and cell apoptosis was also detected. Results Positive rate of STAT4 was 29.2% (50/171) in HCC tissues, 53.2% (91/171) in paraneoplastic liver tissues, 64.9% (24/37) in cirrhosis tissues, and 72.7% (24/33) in normal liver tissues. STAT4 was upregulated in younger patients who were female, with single tumor node, early TNM stage, without portal vein tumor embolus, and α-fetoprotein (AFP)-positive tumors compared with the groups comprising older patients, males, and those with multiple tumor nodes, advanced TNM stage, with portal vein tumor embolus, and AFP negative tumors. Meta-analysis showed STAT4 was correlated with TNM stage (OR =0.50, 95% CI =0.30, 0.83, P=0.008) and age (OR =0.58, 95% CI =0.38, 0.95, P=0.032) in malignant tissues, and with AFP level (OR =1.76, 95% CI =1.06, 2.94, P=0.03) in HCC. STAT4 siRNA promoted growth and suppressed apoptosis of HepG2 cells. Conclusion STAT4 might play a vital role in development of HCC, via influencing cell growth and apoptosis, as a tumor suppressor. PMID:27051307

  19. Comment on ``Three-dimensional photonic-crystal emitter for thermal photovoltaic power generation'' [Appl. Phys. Lett. 83, 380 (2003)

    NASA Astrophysics Data System (ADS)

    Trupke, Thorsten; Würfel, Peter; Green, Martin A.

    2004-03-01

    In a recent article, Lin et al. [Appl. Phys. Lett. 83, 380 (2003)] reported on the light-emitting properties of three-dimensional tungsten photonic crystals and their potential applications as improved thermal emitters in thermophotovoltaic (TPV) systems. Their findings have attracted considerable interest throughout the media and the application of this type of materials has been praised as a potential superior future energy source; e.g., in waste heat-driven electrical generators (http://www.photonics.com). The results of the theoretical modeling in the work of Lin et al. suggest that a TPV system can achieve higher heat to electric energy conversion efficiencies in combination with a three-dimensional tungsten photonic crystal than with any conventional selective thermal emitter. These theoretical results are based on the experimental observation that the photonic crystal, when heated to a given temperature, emits more radiation in certain spectral regimes than a black body of the same temperature. This experimental observation shall briefly be discussed here.

  20. Comment on “Diffusion of n-type dopants in germanium” [Appl. Phys. Rev. 1, 011301 (2014)

    SciTech Connect

    Cowern, N. E. B. Simdyankin, S.; Goss, J. P.; Napolitani, E.; De Salvador, D.; Bruno, E.; Mirabella, S.; Ahn, C.; Bennett, N. S.

    2015-09-15

    The authors of the above paper call into question recent evidence on the properties of self-interstitials, I, in Ge [Cowern et al., Phys. Rev. Lett. 110, 155501 (2013)]. We show that this judgment stems from invalid model assumptions during analysis of data on B marker-layer diffusion during proton irradiation, and that a corrected analysis fully supports the reported evidence. As previously stated, I-mediated self-diffusion in Ge exhibits two distinct regimes of temperature, T: high-T, dominated by amorphous-like mono-interstitial clusters—i-morphs—with self-diffusion entropy ≈30 k, and low-T, where transport is dominated by simple self-interstitials. In a transitional range centered on 475 °C both mechanisms contribute. The experimental I migration energy of 1.84 ± 0.26 eV reported by the Münster group based on measurements of self-diffusion during irradiation at 550 °C < T < 680 °C further establishes our proposed i-morph mechanism.

  1. Comment on ``Preserving the Boltzmann ensemble in replica-exchange molecular dynamics'' [J. Chem. Phys. 129, 164112 (2008)

    NASA Astrophysics Data System (ADS)

    Fukuda, Ikuo

    2010-03-01

    A brief discussion of the ergodic description of constant temperature molecular dynamics (MD) is provided; the discussion is based on the analysis of criticisms raised in a recent paper [B. Cooke and S. C. Schmidler, J. Chem. Phys.129, 164112 (2008)]. In the paper, the following criticisms relating to the basic concepts of constant temperature MD are made in mathematical manners: (I) the Nosé-Hoover (NH) equation is not measure-preserving; (II) NH system and NH chain system are not ergodic under the Boltzmann measure; and (III) the Nosé Hamiltonian system as well as the Nosé-Poincaré Hamiltonian system is not ergodic. In this comment, I show the necessity for the reconsideration of these criticisms. The NH equation is measure-preserving, where the measure carries the Boltzmann-Gibbs density; this fact provides the compatibility between MD equation and the Boltzmann-Gibbs distribution. The arguments advanced in support of the above criticisms are unsound; ergodicities of those systems are still not theoretically judged. I discuss exact ergodic-theoretical expressions appropriate for constant temperature MD, and explain the reason behind the incorrect recognitions.

  2. Toxoplasma gondii Inhibits gamma interferon (IFN-γ)- and IFN-β-induced host cell STAT1 transcriptional activity by increasing the association of STAT1 with DNA.

    PubMed

    Rosowski, Emily E; Nguyen, Quynh P; Camejo, Ana; Spooner, Eric; Saeij, Jeroen P J

    2014-02-01

    The gamma interferon (IFN-γ) response, mediated by the STAT1 transcription factor, is crucial for host defense against the intracellular pathogen Toxoplasma gondii, but prior infection with Toxoplasma can inhibit this response. Recently, it was reported that the Toxoplasma type II NTE strain prevents the recruitment of chromatin remodeling complexes containing Brahma-related gene 1 (BRG-1) to promoters of IFN-γ-induced secondary response genes such as Ciita and major histocompatibility complex class II genes in murine macrophages, thereby inhibiting their expression. We report here that a type I strain of Toxoplasma inhibits the expression of primary IFN-γ response genes such as IRF1 through a distinct mechanism not dependent on the activity of histone deacetylases. Instead, infection with a type I, II, or III strain of Toxoplasma inhibits the dissociation of STAT1 from DNA, preventing its recycling and further rounds of STAT1-mediated transcriptional activation. This leads to increased IFN-γ-induced binding of STAT1 at the IRF1 promoter in host cells and increased global IFN-γ-induced association of STAT1 with chromatin. Toxoplasma type I infection also inhibits IFN-β-induced interferon-stimulated gene factor 3-mediated gene expression, and this inhibition is also linked to increased association of STAT1 with chromatin. The secretion of proteins into the host cell by a type I strain of Toxoplasma without complete parasite invasion is not sufficient to block STAT1-mediated expression, suggesting that the effector protein responsible for this inhibition is not derived from the rhoptries.

  3. Structural Basis of the Inhibition of STAT1 Activity by Sendai Virus C Protein

    PubMed Central

    Oda, Kosuke; Matoba, Yasuyuki; Irie, Takashi; Kawabata, Ryoko; Fukushi, Masaya; Sugiyama, Masanori

    2015-01-01

    ABSTRACT Sendai virus (SeV) C protein inhibits the signal transduction pathways of interferon alpha/beta (IFN-α/β) and IFN-γ by binding to the N-terminal domain of STAT1 (STAT1ND), thereby allowing SeV to escape from host innate immunity. Here we determined the crystal structure of STAT1ND associated with the C-terminal half of the C protein (Y3 [amino acids 99 to 204]) at a resolution of 2.0 Å. This showed that two molecules of Y3 symmetrically bind to each niche created between two molecules of the STAT1ND dimer. Molecular modeling suggested that an antiparallel form of the full-length STAT1 dimer can bind only one Y3 molecule and that a parallel form can bind two Y3 molecules. Affinity analysis demonstrated anticooperative binding of two Y3 molecules with the STAT1 dimer, which is consistent with the hypothetical model that the second Y3 molecule can only target the STAT1 dimer in a parallel form. STAT1 with excess amounts of Y3 was prone to inhibit the dephosphorylation at Tyr701 by a phosphatase. In an electrophoretic mobility shift assay, tyrosine-phosphorylated STAT1 (pY-STAT1) with Y3 associated with the γ-activated sequence, probably as high-molecular-weight complexes (HMWCs), which may account for partial inhibition of a reporter assay from IFN-γ by Y3. Our study suggests that the full-length C protein interferes with the domain arrangement of the STAT1 dimer, leading to the accumulation of pY-STAT1 and the formation of HMWCs. In addition, we discuss the mechanism by which phosphorylation of STAT2 is inhibited in the presence of the C protein after stimulation by IFN-α/β. IMPORTANCE Sendai virus, a paramyxovirus that causes respiratory diseases in rodents, possesses the C protein, which inhibits the signal transduction pathways of interferon alpha/beta (IFN-α/β) and IFN-γ by binding to the transcription factor STAT1. In virus-infected cells, phosphorylation of STAT1 at the Tyr701 residue is potently enhanced, although transcription by STAT1 is

  4. Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response

    PubMed Central

    Ahyi, Ayele-Nati N.; Quinton, Lee J.; Jones, Matthew R.; Ferrari, Joseph D.; Pepper-Cunningham, Zachary A.; Mella, Juan R.; Remick, Daniel G.

    2013-01-01

    The acute-phase response is characteristic of perhaps all infections, including bacterial pneumonia. In conjunction with the acute-phase response, additional biological pathways are induced in the liver and are dependent on the transcription factors STAT3 and NF-κB, but these responses are poorly understood. Here, we demonstrate that pneumococcal pneumonia and other severe infections increase expression of multiple components of the cellular secretory machinery in the mouse liver, including the endoplasmic reticulum (ER) translocon complex, which mediates protein translation into the ER, and the coat protein complexes (COPI and COPII), which mediate vesicular transport of proteins to and from the ER. Hepatocyte-specific mutation of STAT3 prevented the induction of these secretory pathways during pneumonia, with similar results observed following pharmacological activation of ER stress by using tunicamycin. These findings implicate STAT3 in the unfolded protein response and suggest that STAT3-dependent optimization of secretion may apply broadly. Pneumonia also stimulated the binding of phosphorylated STAT3 to promoter regions of secretion-related genes in the liver, supporting a direct role for STAT3 in their transcription. Altogether, these results identify a novel function of STAT3 during the acute-phase response, namely, the induction of secretory machinery in hepatocytes. This may facilitate the processing and delivery of newly synthesized loads of acute-phase proteins, enhancing innate immunity and preventing liver injury during infection. PMID:23460517

  5. Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy.

    PubMed

    Yun, Jang-Hyuk; Park, Sung Wook; Kim, Kyung-Jin; Bae, Jong-Sup; Lee, Eun Hui; Paek, Sun Ha; Kim, Seung U; Ye, Sangkyu; Kim, Jeong-Hun; Cho, Chung-Hyun

    2017-05-01

    Vascular inflammation is characteristic feature of diabetic retinopathy. In diabetic retina, a variety of the pro-inflammatory cytokines are elevated and involved in endothelial dysfunction. STAT3 transcription factor has been implicated in mediating cytokine signaling during vascular inflammation. However, whether and how STAT3 is involved in the direct regulation of the endothelial permeability is currently undefined. Our studies revealed that IL-6-induced STAT3 activation increases retinal endothelial permeability and vascular leakage in retinas of mice through the reduced expression of the tight junction proteins ZO-1 and occludin. In a co-culture model with microglia and endothelial cells under a high glucose condition, the microglia-derived IL-6 induced STAT3 activation in the retinal endothelial cells, leading to increasing endothelial permeability. In addition, IL-6-induced STAT3 activation was independent of ROS generation in the retinal endothelial cells. Moreover, we demonstrated that STAT3 activation downregulates the ZO-1 and occludin levels and increases the endothelial permeability through the induction of VEGF production in retinal endothelial cells. These results suggest the potential importance of IL-6/STAT3 signaling in regulating endothelial permeability and provide a therapeutic target to prevent the pathology of diabetic retinopathy. J. Cell. Physiol. 232: 1123-1134, 2017. © 2016 Wiley Periodicals, Inc.

  6. STAT3 modulates β-cell cycling in injured mouse pancreas and protects against DNA damage

    PubMed Central

    De Groef, S; Renmans, D; Cai, Y; Leuckx, G; Roels, S; Staels, W; Gradwohl, G; Baeyens, L; Heremans, Y; Martens, G A; De Leu, N; Sojoodi, M; Van de Casteele, M; Heimberg, H

    2016-01-01

    Partial pancreatic duct ligation (PDL) of mouse pancreas induces a doubling of the β-cell mass mainly through proliferation of pre-existing and newly formed β-cells. The molecular mechanism governing this process is still largely unknown. Given the inflammatory nature of PDL and inflammation-induced signaling via the signal transducer and activator of transcription 3 (STAT3), the activation and the role of STAT3 in PDL-induced β-cell proliferation were investigated. Duct ligation stimulates the expression of several cytokines that can act as ligands inducing STAT3 signaling and phosphorylation in β-cells. β-Cell cycling increased by conditional β-cell-specific Stat3 knockout and decreased by STAT3 activation through administration of interleukin-6. In addition, the level of DNA damage in β-cells of PDL pancreas increased after deletion of Stat3. These data indicate a role for STAT3 in maintaining a steady state in the β-cell, by modulating its cell cycle and protection from DNA damage. PMID:27336716

  7. Viral microRNAs Target a Gene Network, Inhibit STAT Activation, and Suppress Interferon Responses

    PubMed Central

    Ramalingam, Dhivya; Ziegelbauer, Joseph M.

    2017-01-01

    Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs during latency that are processed to yield ~25 mature microRNAs (miRNAs). We were interested in identifying cellular networks that were targeted by KSHV-miRNAs and employed network building strategies using validated KSHV miRNA targets. Here, we report the identification of a gene network centering on the transcription factor- signal transducer and activator of transcription 3 (STAT3) that is targeted by KSHV miRNAs. KSHV miRNAs suppressed STAT3 and STAT5 activation and inhibited STAT3-dependent reporter activation upon IL6-treatment. KSHV miRNAs also repressed the induction of antiviral interferon-stimulated genes upon IFNα- treatment. Finally, we observed increased lytic reactivation of KSHV from latently infected cells upon STAT3 repression with siRNAs or a small molecule inhibitor. Our data suggest that treatment of infected cells with a STAT3 inhibitor and a viral replication inhibitor, ganciclovir, represents a possible strategy to eliminate latently infected cells without increasing virion production. Together, we show that KSHV miRNAs suppress a network of targets associated with STAT3, deregulate cytokine-mediated gene activation, suppress an interferon response, and influence the transition into the lytic phase of viral replication. PMID:28102325

  8. Aberrant LPL Expression, Driven by STAT3, Mediates Free Fatty Acid Metabolism in CLL Cells

    PubMed Central

    Rozovski, Uri; Grgurevic, Srdana; Bueso-Ramos, Carlos; Harris, David M.; Li, Ping; Liu, Zhiming; Wu, Ji Yuan; Jain, Preetesh; Wierda, William; Burger, Jan; O’Brien, Susan; Jain, Nitin; Ferrajoli, Alessandra; Keating, Michael J.; Estrov, Zeev

    2015-01-01

    While reviewing chronic lymphocytic leukemia (CLL) bone marrow slides we identified cytoplasmic lipid vacuoles in CLL cells but not in normal B cells. Because lipoprotein lipase (LPL), which catalyzes hydrolysis of triglycerides into free fatty acids (FFAs), is aberrantly expressed in CLL, we investigated whether LPL regulates the oxidative metabolic capacity of CLL cells. We found that unlike normal B cells, CLL cells metabolize FFAs. Because STAT3 is constitutively activated in CLL cells and because we identified putative STAT3 binding sites in the LPL promoter, we sought to determine whether STAT3 drives the aberrant expression of LPL. Transfection of luciferase reporter gene constructs driven by LPL promoter fragments into MM1 cells revealed that STAT3 activates the LPL promoter. In addition, chromatin immunoprecipitation (ChIP) confirmed that STAT3 binds to the LPL promoter. Furthermore, transfection of CLL cells with STAT3-shRNA downregulated LPL transcripts and protein levels, confirming that STAT3 activates the LPL gene. Finally, transfection of CLL cells with LPL-siRNAs decreased the capacity of CLL cells to oxidize FFAs and reduced cell viability. PMID:25733697

  9. NAB2-STAT6 Gene Fusion in Meningeal Hemangiopericytoma and Solitary Fibrous Tumor.

    PubMed

    Fritchie, Karen J; Jin, Long; Rubin, Brian P; Burger, Peter C; Jenkins, Sarah M; Barthelmeß, Sarah; Moskalev, Evgeny A; Haller, Florian; Oliveira, Andre M; Giannini, Caterina

    2016-03-01

    Meningeal solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) are considered to be distinct entities in the WHO Classification of CNS Tumours (2007). They harbor NAB2-STAT6 fusions similar to their soft tissue counterparts, supporting the view that they are part of a tumor continuum. We examined 30 meningeal-based tumors originally diagnosed as either SFT or HPC. These showed a spectrum of morphologic features and were diagnosed as SFTs, malignant SFTs, HPCs, or tumors with "intermediate" features. All of the tumors showed nuclear expression of STAT6. SFTs consistently expressed diffuse CD34, while HPCs and intermediate tumors had heterogeneous staining. NAB2-STAT6 fusions were identified in 20 cases, including 7 with exon 4-exon 3, 9 with exon 6-exon 17, and 4 with exon 6-exon 18 fusions. NAB2 exon 4-STAT6 exon 3 fusion correlated with classic SFT morphology and older age and showed a trend toward less mitotic activity; there was also a trend toward more aggressive behavior in tumors lacking NAB2 exon 4-STAT6 exon 3. Thus, despite their clinical and morphologic differences, meningeal-based SFTs, HPCs, and tumors with intermediate features, similar to their soft tissue counterparts, form a histopathologic spectrum unified by STAT6 immunoexpression and NAB2-STAT6 fusion.

  10. STAT3 Undergoes Acetylation-dependent Mitochondrial Translocation to Regulate Pyruvate Metabolism

    PubMed Central

    Xu, Yan S.; Liang, Jinyuan J.; Wang, Yumei; Zhao, Xiang-zhong J.; Xu, Li; Xu, Ye-yang; Zou, Quanli C.; Zhang, Junxun M.; Tu, Cheng-e; Cui, Yan-ge; Sun, Wei-hong; Huang, Chao; Yang, Jing-hua; Chin, Y. Eugene

    2016-01-01

    Cytoplasmic STAT3, after activation by growth factors, translocates to different subcellular compartments, including nuclei and mitochondria, where it carries out different biological functions. However, the precise mechanism by which STAT3 undergoes mitochondrial translocation and subsequently regulates the tricarboxylic acid (TCA) cycle-electron transport chain (ETC) remains poorly understood. Here, we clarify this process by visualizing STAT3 acetylation in starved cells after serum reintroduction or insulin stimulation. CBP-acetylated STAT3 undergoes mitochondrial translocation in response to serum introduction or insulin stimulation. In mitochondria, STAT3 associates with the pyruvate dehydrogenase complex E1 (PDC-E1) and subsequently accelerates the conversion of pyruvate to acetyl-CoA, elevates the mitochondrial membrane potential, and promotes ATP synthesis. SIRT5 deacetylates STAT3, thereby inhibiting its function in mitochondrial pyruvate metabolism. In the A549 lung cancer cell line, constitutively acetylated STAT3 localizes to mitochondria, where it maintains the mitochondrial membrane potential and ATP synthesis in an active state. PMID:28004755

  11. Human metapneumovirus inhibits the IL-6-induced JAK/STAT3 signalling cascade in airway epithelium.

    PubMed

    Mitzel, Dana N; Jaramillo, Richard J; Stout-Delgado, Heather; Senft, Albert P; Harrod, Kevin S

    2014-01-01

    The host cytokine IL-6 plays an important role in host defence and prevention of lung injury from various pathogens, making IL-6 an important mediator in the host's susceptibility to respiratory infections. The cellular response to IL-6 is mediated through a Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signal transduction pathway. Human metapneumovirus (hMPV) is an important causative agent of viral respiratory infections known to inhibit the IFN-mediated activation of STAT1. However, little is known about the interactions between this virus and other STAT signalling cascades. Herein, we showed that hMPV can attenuate the IL-6-mediated JAK/STAT3 signalling cascade in lung epithelial cells. HMPV inhibited a key event in this pathway by impeding the phosphorylation and nuclear translocation of STAT3 in A549 cells and in primary normal human bronchial epithelial cells. Further studies established that hMPV interrupted the IL-6-induced JAK/STAT pathway early in the signal transduction pathway by blocking the phosphorylation of JAK2. By antagonizing the IL-6-mediated JAK/STAT3 pathway, hMPV perturbed the expression of IL-6-inducible genes important for apoptosis, cell differentiation and growth. Infection with hMPV also differentially regulated the effects of IL-6 on apoptosis. Thus, hMPV regulation of these genes could usurp the protective roles of IL-6, and these data provide insight into an important element of viral pathogenesis.

  12. The Effects of Aerosolized STAT1 Antisense Oligodeoxynucleotides on Rat Pulmonary Fibrosis

    PubMed Central

    Wang, Wenjun; Liao, Bin; Zeng, Ming; Zhu, Chen; Fan, Xianming

    2009-01-01

    Previous study showed that aerosolized signal transducer and activator of transcription-1 (STAT1) antisense oligodeoxynucleotide (ASON) inhibited the expression of STAT1 and ICAM-1 mRNA and protein in alveolar macrophages (AMs) and decreased the concentrations of TGF-β, PDGF and TNF-α in bronchioalveolar lavage fluid (BALF) in bleomycin (BLM)-induced rat pulmonary fibrosis. Administration of STAT1 ASON ameliorated alveolitis in rat pulmonary fibrosis. However, further investigations are needed to determine whether there is an effect from administration of STAT1 ASON on fibrosis. This study investigated the effect of aerosolized STAT1 ASON on the expressions of inflammatory mediators, hydroxyproline and type I and type III collagen mRNA in BLM-induced rat pulmonary fibrosis. The results showed that STAT1 ASON applied by aerosolization could ameliorate alveolitis and fibrosis, inhibit the expressions of inflammatory mediators, decrease the content of hydroxyproline, and suppress the expressions of type I and type III collagen mRNA in lung tissue in BLM-induced rat pulmonary fibrosis. These results suggest that aerosolized STAT1 ASON might be considered as a promising new strategy in the treatment of pulmonary fibrosis. PMID:19254480

  13. How should we define STAT3 as an oncogene and as a potential target for therapy?

    PubMed

    Sellier, Hélène; Rébillard, Amélie; Guette, Catherine; Barré, Benjamin; Coqueret, Olivier

    2013-07-01

    Aberrant activation of the STAT3 transcription factor has been reported in a large group of tumors and a strong biological basis now defines this protein as an oncogenic driver. Consequently, STAT3 is considered to be a promising target in the field of cancer therapy. For its inhibition to result in a successful therapeutic approach, the definition of a target tumor population identified by specific and detectable alterations is critical. The canonical activation model of STAT3 relies on a constitutive phosphorylation on its 705 tyrosine site, resulting in its dimerization, nuclear translocation, and the consequent activation of cancer genes. Therefore, it is expected that tumors expressing this phosphorylated form are addicted to STAT3 and will be sensitive to existing drugs which are targeting this dimeric form. However, recent results have shown that STAT3 can function as an oncogene in the absence of this tyrosine phosphorylation. This indicates that different forms of the transcription factor also play an important role in tumor growth and chemotherapy resistance. This complicates the definition of STAT3 as an oncogene and as a potential prognosis and predictive biomarker. The obligation to target a defined tumor type implies that future clinical trials should use a precise definition of STAT3 activation. This will allow tumors addicted to this oncogene to be identified correctly, leading to a strong rationale for patient stratification.

  14. Sol-gel derived contamination resistant antireflective coatings

    NASA Astrophysics Data System (ADS)

    Shen, Jun; Liu, Yuan; Wu, Guangming; Zhou, Bin; Zhang, Zhihua; Zhu, Yumei

    2011-02-01

    Silica-based sol-gel antireflective (AR) optical coatings are critical components for high peak power laser systems. It is well known that water vapor and volatile organic compounds in both the laser bay and target bay environments will reduce the antireflective efficiency and laser-damage resistance of the sol-gel AR coating. In this study, alkylation with organosilanes in the vapor state was investigated. Sol-gel AR coatings were vapor-phase treated with hexamethyldisilazane (HMDS) and trimethylchlorosilane (TMCS) at room temperature, and the resulting post-treated sol-gel AR coatings were tested for their resistance to contamination by a series of volatile organic compounds. Contact angle measurements were taken to discern the degree of silanization. After the vapor treatment of sol-gel AR coatings with organosilanes, the spectral performance of the coatings were analyzed by spectrophotometer, both before and after the exposure to volatile organic compounds. It is found that the coatings treated with ammonia and HMDS show a better contamination resistant capability. After being contaminated 70 hours with hexane, the transmittance of the coatings presents no obvious decrease. And the vapor treatment produces an increase in their damage threshold at 1064 nm (10ns pulse width) as compared to untreated control samples.

  15. Sol-gel derived contamination resistant antireflective coatings

    NASA Astrophysics Data System (ADS)

    Shen, Jun; Liu, Yuan; Wu, Guangming; Zhou, Bin; Zhang, Zhihua; Zhu, Yumei

    2010-10-01

    Silica-based sol-gel antireflective (AR) optical coatings are critical components for high peak power laser systems. It is well known that water vapor and volatile organic compounds in both the laser bay and target bay environments will reduce the antireflective efficiency and laser-damage resistance of the sol-gel AR coating. In this study, alkylation with organosilanes in the vapor state was investigated. Sol-gel AR coatings were vapor-phase treated with hexamethyldisilazane (HMDS) and trimethylchlorosilane (TMCS) at room temperature, and the resulting post-treated sol-gel AR coatings were tested for their resistance to contamination by a series of volatile organic compounds. Contact angle measurements were taken to discern the degree of silanization. After the vapor treatment of sol-gel AR coatings with organosilanes, the spectral performance of the coatings were analyzed by spectrophotometer, both before and after the exposure to volatile organic compounds. It is found that the coatings treated with ammonia and HMDS show a better contamination resistant capability. After being contaminated 70 hours with hexane, the transmittance of the coatings presents no obvious decrease. And the vapor treatment produces an increase in their damage threshold at 1064 nm (10ns pulse width) as compared to untreated control samples.

  16. Opportunity's View After Long Drive on Sol 1770 (Vertical)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings just after driving 104 meters (341 feet) on the 1,770th Martian day, or sol, of Opportunity's surface mission (January 15, 2009).

    This view is presented as a vertical projection with geometric seam correction. North is at the top.

    Tracks from the drive extend northward across dark-toned sand ripples and light-toned patches of exposed bedrock in the Meridiani Planum region of Mars. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches).

    Prior to the Sol 1770 drive, Opportunity had driven less than a meter since Sol 1713 (November 17, 2008), while it used the tools on its robotic arm first to examine a meteorite called 'Santorini' during weeks of restricted communication while the sun was nearly in line between Mars and Earth, then to examine bedrock and soil targets near Santorini.

    The rover's position after the Sol 1770 drive was about 1.1 kilometer (two-thirds of a mile) south southwest of Victoria Crater. Cumulative odometry was 13.72 kilometers (8.53 miles) since landing in January 2004, including 1.94 kilometers (1.21 miles) since climbing out of Victoria Crater on the west side of the crater on Sol 1634 (August 28, 2008).

  17. Opportunity's View After Long Drive on Sol 1770

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings just after driving 104 meters (341 feet) on the 1,770th Martian day, or sol, of Opportunity's surface mission (January 15, 2009).

    Tracks from the drive extend northward across dark-toned sand ripples and light-toned patches of exposed bedrock in the Meridiani Planum region of Mars. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches).

    Prior to the Sol 1770 drive, Opportunity had driven less than a meter since Sol 1713 (November 17, 2008), while it used the tools on its robotic arm first to examine a meteorite called 'Santorini' during weeks of restricted communication while the sun was nearly in line between Mars and Earth, then to examine bedrock and soil targets near Santorini.

    The rover's position after the Sol 1770 drive was about 1.1 kilometer (two-thirds of a mile) south southwest of Victoria Crater. Cumulative odometry was 13.72 kilometers (8.53 miles) since landing in January 2004, including 1.94 kilometers (1.21 miles) since climbing out of Victoria Crater on the west side of the crater on Sol 1634 (August 28, 2008).

    This view is presented as a cylindrical projection with geometric seam correction.

  18. Opportunity's View After Long Drive on Sol 1770 (Polar)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings just after driving 104 meters (341 feet) on the 1,770th Martian day, or sol, of Opportunity's surface mission (January 15, 2009).

    This view is presented as a polar projection with geometric seam correction. North is at the top.

    Tracks from the drive extend northward across dark-toned sand ripples and light-toned patches of exposed bedrock in the Meridiani Planum region of Mars. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches).

    Prior to the Sol 1770 drive, Opportunity had driven less than a meter since Sol 1713 (November 17, 2008), while it used the tools on its robotic arm first to examine a meteorite called 'Santorini' during weeks of restricted communication while the sun was nearly in line between Mars and Earth, then to examine bedrock and soil targets near Santorini.

    The rover's position after the Sol 1770 drive was about 1.1 kilometer (two-thirds of a mile) south southwest of Victoria Crater. Cumulative odometry was 13.72 kilometers (8.53 miles) since landing in January 2004, including 1.94 kilometers (1.21 miles) since climbing out of Victoria Crater on the west side of the crater on Sol 1634 (August 28, 2008).

  19. Sol-gel applications for ceramic membrane preparation

    NASA Astrophysics Data System (ADS)

    Erdem, I.

    2017-02-01

    Ceramic membranes possessing superior properties compared to polymeric membranes are more durable under severe working conditions and therefore their service life is longer. The ceramic membranes are composed of some layers. The support is the layer composed of coarser ceramic structure and responsible for mechanical durability under filtration pressure and it is prepared by consolidation of ceramic powders. The top layer is composed of a finer ceramic micro-structure mainly responsible for the separation of components present in the fluid to be filtered and sol-gel method is a versatile tool to prepare such a tailor-made ceramic filtration structure with finer pores. Depending on the type of filtration (e.g. micro-filtration, ultra-filtration, nano-filtration) aiming separation of components with different sizes, sols with different particulate sizes should be prepared and consolidated with varying precursors and preparation conditions. The coating of sol on the support layer and heat treatment application to have a stable ceramic micro-structure are also important steps determining the final properties of the top layer. Sol-gel method with various controllable parameters (e.g. precursor type, sol formation kinetics, heat treatment conditions) is a practical tool for the preparation of top layers of ceramic composite membranes with desired physicochemical properties.

  20. Time for a Change; Spirit's View on Sol 1843 (Vertical)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Spirit used its navigation camera to take the images that have been combined into this full-circle view of the rover's surroundings during the 1,843rd Martian day, or sol, of Spirit's surface mission (March 10, 2009). South is in the middle. North is at both ends.

    This view is presented as a vertical projection with geometric seam correction. North is at the top.

    The rover had driven 36 centimeters downhill earlier on Sol 1854, but had not been able to get free of ruts in soft material that had become an obstacle to getting around the northeastern corner of the low plateau called 'Home Plate.'

    The Sol 1854 drive, following two others in the preceding four sols that also achieved little progress in the soft ground, prompted the rover team to switch to a plan of getting around Home Plate counterclockwise, instead of clockwise. The drive direction in subsequent sols was westward past the northern edge of Home Plate.

  1. Time for a Change; Spirit's View on Sol 1843 (Polar)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Spirit used its navigation camera to take the images that have been combined into this full-circle view of the rover's surroundings during the 1,843rd Martian day, or sol, of Spirit's surface mission (March 10, 2009). South is in the middle. North is at both ends.

    This view is presented as a polar projection with geometric seam correction. North is at the top.

    The rover had driven 36 centimeters downhill earlier on Sol 1854, but had not been able to get free of ruts in soft material that had become an obstacle to getting around the northeastern corner of the low plateau called 'Home Plate.'

    The Sol 1854 drive, following two others in the preceding four sols that also achieved little progress in the soft ground, prompted the rover team to switch to a plan of getting around Home Plate counterclockwise, instead of clockwise. The drive direction in subsequent sols was westward past the northern edge of Home Plate.

  2. Time for a Change; Spirit's View on Sol 1843 (Stereo)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    [figure removed for brevity, see original site] Left-eye view of a color stereo pair for PIA11973 [figure removed for brevity, see original site] Right-eye view of a color stereo pair for PIA11973

    NASA's Mars Exploration Rover Spirit used its navigation camera to take the images that have been combined into this stereo, full-circle view of the rover's surroundings during the 1,843rd Martian day, or sol, of Spirit's surface mission (March 10, 2009). South is in the middle. North is at both ends.

    This view combines images from the left-eye and right-eye sides of the navigation camera. It appears three-dimensional when viewed through red-blue glasses with the red lens on the left.

    The rover had driven 36 centimeters downhill earlier on Sol 1854, but had not been able to get free of ruts in soft material that had become an obstacle to getting around the northeastern corner of the low plateau called 'Home Plate.'

    The Sol 1854 drive, following two others in the preceding four sols that also achieved little progress in the soft ground, prompted the rover team to switch to a plan of getting around Home Plate counterclockwise, instead of clockwise. The drive direction in subsequent sols was westward past the northern edge of Home Plate.

    This view is presented as a cylindrical-perspective projection with geometric seam correction.

  3. Time for a Change; Spirit's View on Sol 1843

    NASA Technical Reports Server (NTRS)

    2009-01-01

    NASA's Mars Exploration Rover Spirit used its navigation camera to take the images that have been combined into this full-circle view of the rover's surroundings during the 1,843rd Martian day, or sol, of Spirit's surface mission (March 10, 2009). South is in the middle. North is at both ends.

    The rover had driven 36 centimeters downhill earlier on Sol 1854, but had not been able to get free of ruts in soft material that had become an obstacle to getting around the northeastern corner of the low plateau called 'Home Plate.'

    The Sol 1854 drive, following two others in the preceding four sols that also achieved little progress in the soft ground, prompted the rover team to switch to a plan of getting around Home Plate counterclockwise, instead of clockwise. The drive direction in subsequent sols was westward past the northern edge of Home Plate.

    This view is presented as a cylindrical projection with geometric seam correction.

  4. Impurity control studies using SOL flow in DIII-D

    SciTech Connect

    Wade, M.R.; Hogan, J.T.; Isler, R.C.

    1998-11-01

    Experiments on DIII-D have demonstrated the efficacy of using induced scrape-off-layer (SOL) flow to preferentially enrich impurities in the divertor plasma. This SOL flow is produced through simultaneous deuterium gas injection at the midplane and divertor exhaust. Using this SOL flow, an improvement in enrichment (defined as the ratio of impurity fraction in the divertor to that in the plasma core) has been observed for all impurities in trace-level experiments (i.e., impurity level is non-perturbative), with the degree of improvement increasing with impurity atomic number. In the case of argon, exhaust gas enrichment using a modest SOL flow is as high as 17. Using this induced SOL flow technique and argon injection, radiative ELMing H-mode plasmas have been produced that combine high radiation losses (P{sub rad}/P{sub input} > 70%), low core fuel dilution (Z{sub eff} < 1.9), and good core confinement ({tau}{sub E} > 1.0 {tau}{sub E},ITER93H).

  5. Sol-gel technologies for multimode waveguide structures

    NASA Astrophysics Data System (ADS)

    Karioja, Pentti; Kusevic, Maja; Hiltunen, Marianne; Paaso, Janne; Maekinen, Jukka-Tapani; Hiltunen, Jussi A.; Kautio, Kari; Kopola, Harri K.

    2002-06-01

    Lithographic patterning of organic-inorganic hybrid materials processed by the use of sol-gel technology allows for the generation of waveguide structures at low temperatures onto polymer or ceramic substrates. In addition, sol-gel technology provides the possibility to process precision structures, such as, grooves and cavities, which are applicable for the passive alignment of photonic devices. This provides the possibility for the realization of mass-producible photonic circuits onto large-area substrates. At the moment, the most potential applications are systems based on then use of multimode waveguide structures. Actually, when utilizing sol-gel technology, the challenge is how to process homogenous, low-loss and high-aspect-ratio structures. In addition, when aiming to highly mass-producible multimode modules, the key issue is the alignment of photonic devices preferably by the use of passive precision structures. In the future, when the systems need to be more complicated, the modeling of systems requires sophisticated 3D modeling tools. In this paper, the processing of multimode structures with sol-gel technologies is described, and the characterization results of prototype devices are reported. In addition, molding and cofiring technologies potentially applicable for the hybrid integration of photonic modules are reviewed. Finally, the future research aims for the commercialization of photonic modules based on the use of sol-gel technologies are envisioned.

  6. Assessing the Role of STAT3 in DC Differentiation and Autologous DC Immunotherapy in Mouse Models of GBM

    PubMed Central

    Assi, Hikmat; Espinosa, Jaclyn; Suprise, Sarah; Sofroniew, Michael; Doherty, Robert; Zamler, Daniel; Lowenstein, Pedro R.; Castro, Maria G.

    2014-01-01

    Cellular microenvironments, particularly those found in tumors, elicit a tolerogenic DC phenotype which can attenuate immune responses. Central to this process is the STAT3-mediated signaling cascade. As a transcription factor and oncogene, STAT3 promotes the expression of genes which allow tumor cells to proliferate, migrate and evade apoptosis. More importantly, activation of STAT3 in tumor infiltrating immune cells has been shown to be responsible, in part, for their immune-suppressed phenotype. The ability of STAT3 to orchestrate a diverse set of immunosuppressive instructions has made it an attractive target for cancer vaccines. Using a conditional hematopoietic knockout mouse model of STAT3, we evaluated the impact of STAT3 gene ablation on the differentiation of dendritic cells from bone marrow precursors. We also assessed the impact of STAT3 deletion on phagocytosis, maturation, cytokine secretion and antigen presentation by GM-CSF derived DCs in vitro. In addition to in vitro studies, we compared the therapeutic efficacy of DC vaccination using STAT3 deficient DCs to wild type counterparts in an intracranial mouse model of GBM. Our results indicated the following pleiotropic functions of STAT3: hematopoietic cells which lacked STAT3 were unresponsive to Flt3L and failed to differentiate as DCs. In contrast, STAT3 was not required for GM-CSF induced DC differentiation as both wild type and STAT3 null bone marrow cells gave rise to similar number of DCs. STAT3 also appeared to regulate the response of GM-CSF derived DCs to CpG. STAT3 null DCs expressed high levels of MHC-II, secreted more IL-12p70, IL-10, and TNFα were better antigen presenters in vitro. Although STAT3 deficient DCs displayed an enhanced activated phenotype in culture, they elicited comparable therapeutic efficacy in vivo compared to their wild type counterparts when utilized in vaccination paradigms in mice bearing intracranial glioma tumors. PMID:24806510

  7. Necdin, a negative growth regulator, is a novel STAT3 target gene down-regulated in human cancer.

    PubMed

    Haviland, Rachel; Eschrich, Steven; Bloom, Gregory; Ma, Yihong; Minton, Susan; Jove, Richard; Cress, W Douglas

    2011-01-01

    Cytokine and growth factor signaling pathways involving STAT3 are frequently constitutively activated in many human primary tumors, and are known for the transcriptional role they play in controlling cell growth and cell cycle progression. However, the extent of STAT3's reach on transcriptional control of the genome as a whole remains an important question. We predicted that this persistent STAT3 signaling affects a wide variety of cellular functions, many of which still remain to be characterized. We took a broad approach to identify novel STAT3 regulated genes by examining changes in the genome-wide gene expression profile by microarray, using cells expressing constitutively-activated STAT3. Using computational analysis, we were able to define the gene expression profiles of cells containing activated STAT3 and identify candidate target genes with a wide range of biological functions. Among these genes we identified Necdin, a negative growth regulator, as a novel STAT3 target gene, whose expression is down-regulated at the mRNA and protein levels when STAT3 is constitutively active. This repression is STAT3 dependent, since inhibition of STAT3 using siRNA restores Necdin expression. A STAT3 DNA-binding site was identified in the Necdin promoter and both EMSA and chromatin immunoprecipitation confirm binding of STAT3 to this region. Necdin expression has previously been shown to be down-regulated in a melanoma and a drug-resistant ovarian cancer cell line. Further analysis of Necdin expression demonstrated repression in a STAT3-dependent manner in human melanoma, prostate and breast cancer cell lines. These results suggest that STAT3 coordinates expression of genes involved in multiple metabolic and biosynthetic pathways, integrating signals that lead to global transcriptional changes and oncogenesis. STAT3 may exert its oncogenic effect by up-regulating transcription of genes involved in promoting growth and proliferation, but also by down-regulating expression

  8. Optimization and utilization of the SureFire phospho-STAT5 assay for a cell-based screening campaign.

    PubMed

    Binder, Christina; Lafayette, Amy; Archibeque, Ivonne; Sun, Yu; Plewa, Cherylene; Sinclair, Angus; Emkey, Renee

    2008-02-01

    The family of signal transducers and activators of transcription (STATs) consists of seven transcription factors that respond to a variety of cytokines, hormones, and growth factors. STATs are activated by tyrosine phosphorylation, which results in their dimerization and translocation into the nucleus where they exert their effect on transcription of regulated target genes. The phosphorylation of STATs is mediated mainly by Janus kinases (JAKs). The JAK/STAT pathway plays a critical role in hematopoietic and immune cell function. Here we focus on one member of the STAT family, STAT5. STAT5 is phosphorylated by several JAKs, including Jak3, Jak2, and Tyk2, in response to interleukin-2, erythropoietin (EPO), and interleukin-22, respectively. Activation of STAT5 is essential to T cell development and has been associated with hematologic malignancies. Therefore, the ability to assess STAT5 phosphorylation is important for discovery efforts targeting these indications. The assay formats available to detect phosphorylated STAT5 (pSTAT5) are relatively low throughput and involve lengthy protocols. These formats include western blot analysis, enzyme-linked immunosorbent assay (ELISA), and flow cytometry. The SureFire (Perkin Elmer, Waltham, MA) pSTAT5 assay is a homogeneous assay that utilizes AlphaScreen (Perkin Elmer) technology to detect pSTAT5 in cell lysates. We have used this assay format to evaluate EPO-induced STAT5 phosphorylation in HEL cells and successfully complete a small-scale screening campaign to identify inhibitors of this event. The results obtained in these studies demonstrate that the SureFire pSTAT5 assay is a robust, reliable assay format that is amenable to high-throughput screening (HTS) applications.

  9. Tofacitinib regulates synovial inflammation in psoriatic arthritis, inhibiting STAT activation and induction of negative feedback inhibitors

    PubMed Central

    Gao, W; McGarry, T; Orr, C; McCormick, J; Veale, D J; Fearon, U

    2016-01-01

    Background Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterised by synovitis and destruction of articular cartilage/bone. Janus-kinase and signal transducer and activator of transcription (JAK-STAT) signalling pathway is implicated in the pathogenesis of PsA. Objectives To examine the effect of tofacitinib (JAK inhibitor) on proinflammatory mechanisms in PsA. Methods Primary PsA synovial fibroblasts (PsAFLS) and ex vivo PsA synovial explants were cultured with tofacitinib (1 µM). PhosphoSTAT3 (pSTAT3), phosphoSTAT1 (pSTAT1), suppressor of cytokine signaling-3 (SOCS3), protein inhibitor of activated Stat3 (PIAS3) and nuclear factor kappa B cells (NFκBp65) were quantified by western blot. The effect of tofacitinib on PsAFLS migration, invasion, Matrigel network formation and matrix metallopeptidase (MMP)2/9 was quantified by invasion/migration assays and zymography. Interleukin (IL)-6, IL-8, IFN-gamma-inducible protein 10 (IP-10) monocyte chemoattractant protein (MCP)-1, IL-17, IL-10, MMP3 and tissue inhibitor of metalloproteinases 3 (TIMP3) were assessed by ELISA. Results Tofacitinib significantly decreased pSTAT3, pSTAT1, NFκBp65 and induced SOCS3 and PIAS3 expression in PsAFLS and synovial explant cultures (p<0.05). Functionally, PsAFLS invasion, network formation and migration were inhibited by tofacitinib (all p<0.05). In PsA explant, tofacitinib significantly decreased spontaneous secretion of IL-6, IL-8, MCP-1, MMP9/MMP2, MMP3 (all p<0.05) and decreased the MMP3/TIMP3 ratio (p<0.05), with no effect observed for IP-10 or IL-10. Conclusions This study further supports JAK-STAT inhibition as a therapeutic target for the treatment of PsA. PMID:26353790

  10. Arctigenin enhances chemosensitivity of cancer cells to cisplatin through inhibition of the STAT3 signaling pathway.

    PubMed

    Yao, Xiangyang; Zhu, Fenfen; Zhao, Zhihui; Liu, Chang; Luo, Lan; Yin, Zhimin

    2011-10-01

    Arctigenin is a dibenzylbutyrolactone lignan isolated from Bardanae fructus, Arctium lappa L, Saussureamedusa, Torreya nucifera, and Ipomea cairica. It has been reported to exhibit anti-inflammatory activities, which is mainly mediated through its inhibitory effect on nuclear transcription factor-kappaB (NF-κB). But the role of arctigenin in JAK-STAT3 signaling pathways is still unclear. In present study, we investigated the effect of arctigenin on signal transducer and activator of transcription 3 (STAT3) pathway and evaluated whether suppression of STAT3 activity by arctigenin could sensitize cancer cells to a chemotherapeutic drug cisplatin. Our results show that arctigenin significantly suppressed both constitutively activated and IL-6-induced STAT3 phosphorylation and subsequent nuclear translocation in cancer cells. Inhibition of STAT3 tyrosine phosphorylation was found to be achieved through suppression of Src, JAK1, and JAK2, while suppression of STAT3 serine phosphorylation was mediated by inhibition of ERK activation. Pervanadate reversed the arctigenin-induced downregulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, arctigenin can obviously induce the expression of the PTP SHP-2. Furthermore, the constitutive activation level of STAT3 was found to be correlated to the resistance of cancer cells to cisplatin-induced apoptosis. Arctigenin dramatically promoted cisplatin-induced cell death in cancer cells, indicating that arctigenin enhanced the sensitivity of cancer cells to cisplatin mainly via STAT3 suppression. These observations suggest a novel anticancer function of arctigenin and a potential therapeutic strategy of using arctigenin in combination with chemotherapeutic agents for cancer treatment.

  11. Validation of the i-STAT system for the analysis of blood parameters in fish

    PubMed Central

    Harter, T. S.; Shartau, R. B.; Brauner, C. J.; Farrell, A. P.

    2014-01-01

    Portable clinical analysers, such as the i-STAT system, are increasingly being used for blood analysis in animal ecology and physiology because of their portability and easy operation. Although originally conceived for clinical application and to replace robust but lengthy techniques, researchers have extended the use of the i-STAT system outside of humans and even to poikilothermic fish, with only limited validation. The present study analysed a range of blood parameters [pH, haematocrit (Hct), haemoglobin (Hb), HCO3−, partial pressure of CO2 (PCO2), partial pressure of O2 (PO2), Hb saturation (sO2) and Na+ concentration] in a model teleost fish (rainbow trout, Oncorhynchus mykiss) using the i-STAT system (CG8+ cartridges) and established laboratory techniques. This methodological comparison was performed at two temperatures (10 and 20°C), two haematocrits (low and high) and three PCO2 levels (0.5, 1.0 and 1.5%). Our results indicate that pH was measured accurately with the i-STAT system over a physiological pH range and using the i-STAT temperature correction. Haematocrit was consistently underestimated by the i-STAT, while the measurements of Na+, PCO2, HCO3− and PO2 were variably inaccurate over the range of values typically found in fish. The algorithm that the i-STAT uses to calculate sO2 did not yield meaningful results on rainbow trout blood. Application of conversion factors to correct i-STAT measurements is not recommended, due to significant effects of temperature, Hct and PCO2 on the measurement errors and complex interactions may exist. In conclusion, the i-STAT system can easily generate fast results from rainbow trout whole blood, but many are inaccurate values. PMID:27293658

  12. Dasatinib (BMS-354825) inhibits Stat5 signaling associated with apoptosis in chronic myelogenous leukemia cells.

    PubMed

    Nam, Sangkil; Williams, Ann; Vultur, Adina; List, Alan; Bhalla, Kapil; Smith, David; Lee, Francis Y; Jove, Richard

    2007-04-01

    Dasatinib (BMS-354825) is a novel, oral, potent, multi-targeted kinase inhibitor of Bcr-Abl and Src family kinases (SFK) and is a promising cancer therapeutic agent. Preclinical data indicate that dasatinib is 325-fold more potent than imatinib against cells expressing wild-type Bcr-Abl, and that dasatinib is active against 18 of 19 Bcr-Abl mutations known to cause imatinib resistance. Phase I clinical data show that dasatinib is well tolerated and highly effective for the treatment of imatinib-resistant/imatinib-intolerant chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia. However, the molecular mechanism of action of dasatinib is not fully understood. In this study, we confirm that dasatinib inhibits tyrosine phosphorylation of SFKs, including Src, Hck, and Lyn, in K562 human CML cells. Significantly, downstream signal transducer and activator of transcription 5 (Stat5) signaling is also blocked by dasatinib as shown by decreases in levels of phosphorylated Stat5 and Stat5 DNA-binding activities. In addition, dasatinib down-regulates expression of Stat5 target genes, including Bcl-x, Mcl-1, and cyclin D1. Consistent with these results, blockade of Stat5 signaling by dasatinib is accompanied by inhibition of cell proliferation and induction of apoptosis. Surprisingly, Stat5 DNA-binding activities are enhanced with increasing cell density, which is associated with resistance to apoptosis by dasatinib. Our findings indicate that inhibition of Stat5 signaling downstream of Bcr-Abl/SFKs contributes to the action of dasatinib, and, conversely, that increasing cell density up-regulates Stat5 activation and confers resistance to dasatinib. Moreov