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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. (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!

  3. 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!

  4. 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.

  5. 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.

  6. 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!

  7. 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!

  8. 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!

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Preface: phys. stat. sol. (a) 202/7

    NASA Astrophysics Data System (ADS)

    Pollak, Fred H.; Misiewicz, Jan; Sitarek, Piotr

    2005-05-01

    We have recently observed a growing interest in using the powerful technique of optical modulation spectroscopy. These applications are related mostly to the characterization of low dimensional semiconductor structures and devices based on them.The International Workshop on Modulation Spectroscopy of Semiconductor Structures (MS3) at the beginning of July 2004 gathered in Wrocaw (in the southwest part of Poland) almost 40 participants, half of them from abroad. The 8 invited and 16 contributed talks were presented by the leaders of research teams from the USA, Japan, Taiwan, Canada, Germany, France, the Netherlands, Sweden, Ireland, Russia, Lithuania and Poland. Part of the MS3 workshop was held at the Laboratory of Advanced Optical Spectroscopy, Institute of Physics, Wrocaw University of Technology, where discussions on technical matter of the modulation spectroscopy were carried out in a relaxing atmosphere over a cup of coffee.The topics of the MS3 workshop included: advantages of photoreflectance, electroreflectance, contactless electroreflectance, thermoreflectance, differential reflectance and wavelength-modulated surface photovoltage spectroscopy. The applications of the above methods to investigate transistor, diode and laser structures including VCSELs, low dimensional structures of both wings of the spectrum, i.e. wide band gap materials like GaN, AlGaN, ZnO and low band gap materials such as GaInN(Sb)As, InAs, InSb, and FeSi2 were demonstrated.It is our great pleasure to publish the most interesting of the MS3 workshop presentations in this issue of physica status solidi (a).The organizers acknowledge Wrocaw University of Technology, the Center of Exellence CEPHONA from the Institute of Electron Technology in Warsaw and the Polish Committee for Scientific Research for financial support of the workshop.

  14. Preface: phys. stat. sol. (b) 242/1

    NASA Astrophysics Data System (ADS)

    Ginzburg, V. L.; Maksimov, E. G.

    2005-01-01

    We have accepted with great pleasure the suggestion of the Guest Editor Miodrag Kuli to write a short preface to the special issue of this journal, which is devoted to the role played by electron-phonon interaction (EPI) in high-temperature superconductors (HTSC). From the very beginning, it was absolutely clear to us that there is no metal in which the EPI could be ignored, and high-temperature superconducting compounds cannot be an exception in this respect. We expressed this opinion, in particular, in our early Review Article [1] and in the talk [2] given at the Grenoble M2S HTSC Conference in 1994. We would like to emphasize that we were not in isolation. There have been many other researchers, some authors of this issue among them, who have also considered the EPI as an essential part of the physics of high-temperature superconductors. However, a large part of researchers in the field, including a few famous scientists, have considered the EPI to be irrelevant to high-temperature superconductivity. Up to now, we do not understand the scientific basis for such an opinion. Moreover, that point of view has never been shared by some other famous scientists; in this respect mention should be made of J. Friedel and A. A. Abrikosov.Turning back to physics, we would like to point out some features of high-temperature superconducting cuprates, which should lead to the existence of a strong EPI in these materials. First of all, it is the proximity of these compounds, even in the optimally doped case, to the layered ionic crystals. This fact has been emphasized in our early publications as well as in many papers by other authors, and it is discussed in detail in the Review Article by C. Falter published in this issue. There are other approaches to the HTSC compounds, which allow to consider that a strong EPI exists. They are also based on some peculiarities in the crystalline and chemical structure of these compounds, in particular, on their multiphase nanoscale structure. This point is discussed by J. Phillips in this issue.There are also many experimental indications in favor of the existence of a strong EPI in the HTSC cuprates. For example, the behavior of the electron relaxation, the peculiarities of the phonon spectra, the interaction of the Josephson current with phonons, and the electron mass renormalization. All these phenomena have been discussed in the recent Review Articles [3, 4]. Currently, additional evidence was provided which has thrown new light on the role played by the EPI in HTSC systems. These are the ARPES experiments conducted by the Stanford group, which have given an unambiguous proof of the electron mass renormalization due to the EPI. A Review Article of this group by T. Cuk et al. is also presented in this issue. We should also mention the contribution of L. Pintschovius who presented new interesting results on the electron-phonon coupling effects observed by means of inelastic neutron scattering.A comprehensive discussion of a major part of the electron-phonon coupling effects presented in the Review Articles [1, 3] has been based on the traditional approach of the Eliashberg type. Up to now, we consider this approach to be quite suitable for pursuing a number of goals, mainly for describing properties of the normal state. Nevertheless, we do not disclaim the importance of more detailed investigations of the EPI, which take into account the strong anisotropy, the interplay between electron-phonon and electron-electron interaction, and the non-adiabatic effects. Four Review Articles in this issue, by Schneider, by Rösch, Han, Gunnarsson and Crespi, by Kuli and Dolgov, and by Cappelluti and Pietronero are devoted to different aspects of these problems.To conclude, we would like to emphasize that the main problem related to the mechanism of superconductivity in the HTSC cuprates is the interplay between the strong EPI and the electron exchange and correlation. Unfortunately, previous work did not crack this problem and much effort should be made in the future. We hope that the publication of this issue will aid to attract the attention of many researchers to the investigation of unsolved problems of the EPI in HTSC systems.

  15. 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.

  16. 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!

  17. 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!

  18. Preface: phys. stat. sol. (a) 201/8

    NASA Astrophysics Data System (ADS)

    Shin, Sung-Chul

    2004-06-01

    The KMS/SOMMA Meeting 2003 was held 3-6 December 2003 at Spapia Hotel, Daejeon, Korea. It was the 5th SOMMA (International Symposium on Magnetic Materials and Applications) organized by ReCAMM (Research Center for Advanced Magnetic Materials) of Chungnam National University. Since 2002, the Korean Magnetics Society (KMS) winter conference has been jointly held with SOMMA. This was the second time to have a KMS/SOMMA joint meeting. The main objective of the meeting was to provide an international forum to discuss up-to-date results on magnetism and magnetic materials. The conference brought together 360 participants from 12 countries. Sessions of the meeting were: Theory and Fundamentals, Magnetic Random Access Memory, Spintronics, Information Storage, Nanostructured Materials, Sensors, and Interdisciplinary. In these seven sessions, 325 papers were presented including 66 oral and 259 poster presentations. Since the symposium was held in Korea, this enabled a large number of Asian scientists to attend: 239 from Korea, 41 from Japan, 7 from Taiwan, and 5 from China.The conference program had 25 invited and plenary speakers. They were Y. Ando (Tohoku U.), M. Inoue (Toyohashi U. Tech), H. Kubota (Tohoku U.), K. Mohri (Nagoya U.), M. Sahashi, M. Takahashi, K. Takanashi, M. Tsunoda (Tohoku U.), and H. Yoda (Toshiba) from Japan; A. J. Freeman (Northwestern U.), A. T. Hanbicki (NRL), F. B. Humphrey (Boston U.), and S. Sun (IBM) from the USA; J. D. Boeck (IMEC, Belgium), B. Dieny (CEA, France), N. Garcia (CSIS, Spain), G. Reiss (Bielefeld U., Germany), T. Stobiecki (U. M. & M. Krakow, Poland), and M. Wolfram (Singulus Tech, Germany) from Europe; C. G. Kim, D. J. Kim (CNU), T. W. Kim (SAIT), S. H. Lim (KIST), Sung-Chul Shin (KAIST), and Yoon Hee Chung (POSTEC) from Korea.For the first time, the SOMMA Proceedings appear in physica status solidi. The Editors hope that the Proceedings could provide chances for deeper and wider understanding of the presentations as well as for enhanced relationship between all participants. We deeply appreciate the help of the editorial staff of physica status solidi for their efficient and kind help during the paper preparations and publications.Finally, we would like to take this opportunity to thank all members of the Advisory Committee, Organizing Committee, referees, and KMS staff for their effort before, during, and after the meeting.

  19. Preface: phys. stat. sol. (b) 241/7

    NASA Astrophysics Data System (ADS)

    Shin, Sung-Chul

    2004-06-01

    The KMS/SOMMA Meeting 2003 was held 3-6 December 2003 at Spapia Hotel, Daejeon, Korea. It was the 5th SOMMA (International Symposium on Magnetic Materials and Applications) organized by ReCAMM (Research Center for Advanced Magnetic Materials) of Chungnam National University. Since 2002, the Korean Magnetics Society (KMS) winter conference has been jointly held with SOMMA. This was the second time to have a KMS/SOMMA joint meeting.The main objective of the meeting was to provide an international forum to discuss up-to-date results on magnetism and magnetic materials. The conference brought together 360 participants from 12 countries. Sessions of the meeting were: Theory and Fundamentals, Magnetic Random Access Memory, Spintronics, Information Storage, Nanostructured Materials, Sensors, and Interdisciplinary. In these seven sessions, 325 papers were presented including 66 oral and 259 poster presentations. Since the symposium was held in Korea, this enabled a large number of Asian scientists to attend: 239 from Korea, 41 from Japan, 7 from Taiwan, and 5 from China.The conference program had 25 invited and plenary speakers. They were Y. Ando (Tohoku U.), M. Inoue (Toyohashi U. Tech), H. Kubota (Tohoku U.), K. Mohri (Nagoya U.), M. Sahashi, M. Takahashi, K. Takanashi, M. Tsunoda (Tohoku U.), and H. Yoda (Toshiba) from Japan; A. J. Freeman (Northwestern U.), A. T. Hanbicki (NRL), F. B. Humphrey (Boston U.), and S. Sun (IBM) from the USA; J. D. Boeck (IMEC, Belgium), B. Dieny (CEA, France), N. Garcia (CSIS, Spain), G. Reiss (Bielefeld U., Germany), T. Stobiecki (U. M. & M. Krakow, Poland), and M. Wolfram (Singulus Tech, Germany) from Europe; C. G. Kim, D. J. Kim (CNU), T. W. Kim (SAIT), S. H. Lim (KIST), Sung-Chul Shin (KAIST), and Yoon Hee Chung (POSTEC) from Korea.For the first time, the SOMMA Proceedings appear in physica status solidi. The Editors hope that the Proceedings could provide chances for deeper and wider understanding of the presentations as well as for enhanced relationship between all participants. We deeply appreciate the help of the editorial staff of physica status solidi for their efficient and kind help during the paper preparations and publications.Finally, we would like to take this opportunity to thank all members of the Advisory Committee, Organizing Committee, referees, and KMS staff for their effort before, during, and after the meeting.

  20. 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.

  1. 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).

  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. (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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. Stats About Paralysis

    MedlinePlus

    ... Paralysis Get Support Get Involved Research Events Blog & Forum About Us Donate Living with Paralysis > Stats about ... in your area Join the discussion in our forum This project was supported, in part by grant ...

  18. Using STAT properly.

    PubMed

    Wesp, William

    2006-01-01

    The misuse of the term STAT has long been a problem in many hospitals. Instead of being the universal word for "immediate," it has become a convenient phrase used, in some cases, to get what the physician wants now. Although the principles of this article may be applied to many modalities in the healthcare field, this article deals solely with portable chest x-rays performed at the University of Minnesota Medical Center, Fairview in Minneapolis. The diagnostic radiology department performed a 2-week analysis of orders in August 2004. The results showed that 74% of all portable chest x-rays were ordered as STAT. The manager, along with a staff radiologist, then created a list of clinical reasons that were appropriate for STAT, ASAP, or Routine orders. Then, there was a 2-week period of time delegated for education, during which the list was brought to the nurse managers of several patient care areas as well as some chief residents at the university's medical school. These individuals then shared the list with their staff. A second analysis conducted in November 2004 showed that an 11% decrease had been achieved. Given that 20,000 portable chest x-rays are performed at the medical center annually, the figure represents a 2,200 reduction in STAT portables per year. With the success of this endeavor, the radiology department piloted a second program to further decrease the number of STAT orders. Since the radiology department was using computed radiography (CR) and a picture archiving and communication system (PACS), research began to unearth the response times. The idea was to advertise to physicians how fast they could get their images, using the theory that if the times were quick enough, perhaps there would less of a tendency to order STATs. The results showed that a STAT order could be completed and viewable on PACS in an average of 17 minutes, and an ASAP in 28 minutes. A poster advertising these response times was generated and distributed to the nurse managers

  19. 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.

  20. 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 ...

  1. 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.

  2. Preassociation of STAT1 with STAT2 and STAT3 in separate signalling complexes prior to cytokine stimulation.

    PubMed

    Stancato, L F; David, M; Carter-Su, C; Larner, A C; Pratt, W B

    1996-02-23

    A variety of cytokines and growth factors act through an induction of gene expression mediated by a family of latent transcription factors called STAT (signal transducers and activators of transcription) proteins. Ligand-induced tyrosine phosphorylation of the STATs promotes their homodimer and heterodimer formation and subsequent nuclear translocation. We demonstrate here that STAT protein heterocomplexes exist prior to cytokine treatment. When unstimulated HeLa cells are ruptured in hypotonic buffer without salt or detergent, immunoadsorption of either STAT1 or STAT2 from the resulting cytosol yields coimmunoadsorption of the other STAT protein. Similarly, STAT1-STAT3 heterocomplexes are coimmunoadsorbed from hypotonic cytosol. STAT1 and STAT2 or STAT1 and STAT3 translated in reticulocyte lysate spontaneously form heterocomplexes when the translation lysates are mixed at 0 degrees C. Our data suggest that interferon-alpha /beta-induced tyrosine phosphorylation increases the stability of a preexisting, latent, STAT1-STAT2 signaling complex. Newly translated STAT1 binds in equilibrium fashion to STAT2 and STAT3, but we show that STAT2 and STAT3 exist in separate heterocomplexes with STAT1, consistent with a model in which STAT1 contains a common binding site for other STAT proteins.

  3. MAC-bridging for multi-PHYs communication in BAN.

    PubMed

    Ullah, Sana; Khan, Pervez; Ullah, Niamat; Kwak, Kyung Sup

    2010-01-01

    Body Area Network (BAN) is a collection of low-power, miniaturised, and intelligent sensor nodes that are used for unobtrusive and ambulatory health monitoring of a patient without any additional constraints. These nodes operate on different frequency bands or Multiple Physical Layers (Multi-PHYs). Additionally, some BAN applications demand a logical connection between different nodes working on different Multi-PHYs. In this paper, the idea of controlling Multi-PHYs using one MAC protocol is introduced. Unlike existing procedures where different nodes working on different channels are connected at the link layer bridging/switching, the proposed procedure called bridging logically connects them at the MAC layer. In other words, the bridge is used to relay or filter packets between different PHYs in the same BAN. Numerical approximations are presented to analyze the stochastic behaviour of the bridges, all of them having Multi-PHYs interfaces. The MICS and the ISM bands are regarded as PHY1 and PHY2, respectively. The performance results are presented for PHY2 (given that data is already received from PHY1) in terms of probability of successful transmission, number of failed requests, power consumption, and delay. Simulations are conducted to validate the analytical results. It can be seen that the deployment of multiple bridges along with the corresponding nodes allows Multi-PHYs communication with high transmission probability, low power consumption, and tolerable delay.

  4. Sol-gel science

    SciTech Connect

    Brinker, C.J. ); Scherer, G.W. )

    1990-01-01

    Although the science and technology of sol-gel processing has experienced enormous growth in the last decade, few books have been available to help researchers cope with the flood of results published in various journals and conference proceedings. This book presents and understanding of sol-gel processing. Following the sol-gel processing sequence from beginning to end, it includes discussions on the chemistry of hydrolysis and condensation of metalorganics and inorganic salts, the growth of polymeric or particulate species in sols, gelation, aging of gels, drying, structure of gels, and sintering. In addition, it compares the properties of gel-derived and conventionally prepared ceramics, examines films in detail, and presents a variety of applications.

  5. 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.

  6. STATs profiling reveals predominantly-activated STAT3 in cholangiocarcinoma genesis and progression.

    PubMed

    Dokduang, Hasaya; Techasen, Anchalee; Namwat, Nisana; Khuntikeo, Narong; Pairojkul, Chawalit; Murakami, Yoshinori; Loilome, Watcharin; Yongvanit, Puangrat

    2014-10-01

    We investigated the aberrant expression of the STAT family in humans and liver fluke (Opisthorchis viverrini, Ov)-induced hamster cholangiocarcinoma (CCA) tissues. The expression and phosphorylation of STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6 in human hamster CCA tissues were immunohistochemistry-profiled. Localizations of STAT5 in macrophages and lipopolysaccharide (LPS)-induced macrophage-conditioned media mediated STAT3 activation in CCA cells were demonstrated. The expressions of STAT 1-4 and 6 were detected in the cytoplasm of hyperplastic bile ducts and tumor cells, whereas STAT5a and STAT5b were observed in macrophages and connective tissues surrounding tumor, respectively. The expressions of STAT3 and STAT5b were significantly observed in tumors with a poorer histological differentiation. STAT3 expression was significantly associated with shorter survival of CCA patients and was predominately activated in CCA cell lines. In the CCA-hamsters, STATs expression was gradually increased along the carcinogenesis, especially at 30 days post-infection in which the inflammatory response was markedly observed, showing the correlation between the inflammation and STATs activation. Moreover, LPS-induced macrophage-conditioned media could mediate STAT3 activation in CCA cells. STAT3 is the major STAT, which plays roles in the inflammation that contributes to CCA carcinogenesis and progression and may serve as a marker for a poor prognosis of CCA. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  7. 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.

  8. 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

  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. Regulation of STAT signalling by proteolytic processing.

    PubMed

    Hendry, Lisa; John, Susan

    2004-12-01

    Interaction of cytokines with their cognate receptors leads to the activation of latent transcription factors, the signal transducer and activator of transcription (STAT) proteins. Numerous studies have identified the critical roles played by STAT proteins in regulating cell proliferation, differentiation and survival. Consequently, the activity of STAT proteins is negatively regulated by a variety of different mechanisms, which include alternative splicing, covalent modifications, protein-protein interactions with negative regulatory proteins and proteolytic processing by proteases. Cleavage of STAT proteins by proteases results in the generation of C-terminally truncated proteins, called STATgamma, which lack the transactivation domain and behave as functional dominant-negative proteins. Currently, STATgamma isoforms have been identified for Stat3, Stat5a, Stat5b and Stat6 in different cellular contexts and biological processes. Evidence is mounting for the role of as yet unidentified serine proteases in the proteolytic processing of STAT proteins, although at least one cysteine protease, calpain is also known to cleave these STATs in platelets and mast cells. Recently, studies of acute myeloid leukaemia and cutaneous T cell lymphoma patients have revealed important roles for the aberrant expression of Stat3gamma and Stat5gamma proteins in the pathology of these diseases. Together, these findings indicate that proteolytic processing is an important mechanism in the regulation of STAT protein biological activity and provides a fertile area for future studies.

  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. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Nanocrystal/sol-gel nanocomposites

    DOEpatents

    Petruska, Melissa A [Los Alamos, NM; Klimov, Victor L [Los Alamos, NM

    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

  6. Nanocrystal/sol-gel nanocomposites

    DOEpatents

    Petruska, Melissa A [Los Alamos, NM; Klimov, Victor L [Los Alamos, NM

    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.

  7. 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.

  8. 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.

  9. Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation.

    PubMed

    Wen, Z; Zhong, Z; Darnell, J E

    1995-07-28

    Stat1 and Stat3 are latent transcriptional factors activated initially through phosphorylation on single tyrosine residues induced by cytokine and growth factor occupation of cell surface receptors. Here we show that phosphorylation on a single serine (residue 727) in each protein is also required for maximal transcriptional activity. Both cytokines and growth factors are capable of inducing the serine phosphorylation of Stat1 and Stat3. These experiments show that gene activation by Stat1 and Stat3, which obligatorily require tyrosine phosphorylation to become active, also depends for maximal activation on one or more of the many serine kinases.

  10. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Thermosensitive periodontal sol of ciprofloxacin hydrochloride and serratiopeptidase: Pharmaceutical and mechanical analysis

    PubMed Central

    Singh, Kushal Pal; Chhabra, Gulshan; Sharma, Vijay; Pathak, Kamla

    2014-01-01

    Aim: The aim of the present work was to explore the development of a dual-controlled release periodontal system of a potent broad spectrum first-generation fluoroquinolone, ciprofloxacin, and the anti-inflammatory enzyme serratiopeptidase (STP). Materials and Methods: Based on 32 full factorial design, thermoreversible periodontal sols capable of controlled dual delivery of ciprofloxacin hydrochloride and STP were designed using pluronic F127 and carbopol 934P as thermosensitive gelling polymers. Sol gel transition characteristics, %cumulative drug release at 48th h and exvivo mucoadhesive strength were designated as dependent responses. The sols were mucoadhesive, syringeable, and inverted into gels at simulated periodontal cavity temperature. Results: F9 with optimal drug release was identified as the best formulation. Extra design check point generated using Design Expert software 8.02 (Stat-Ease, USA) validated the experimental design. Textural analysis revealed that the developed sols were syringeable and spreadable enough for periodontal treatment so it can be expected that hardness and compressibility of sols would pose no problem during clinical application. The in vitro release behavior exhibited controlled release of both cipro HCl and STP (>90% release). Conclusion: A dual-controlled release thermoreversible periodontal sol of ciproflaxin and STP was successfully developed. Incorporation of STP as anti-inflammatory agent has the potential of developing a therapeutically efficacious system of cipro HCl for treatment of periodontal inflammatory anaerobic infections. PMID:24678456

  12. Thermosensitive periodontal sol of ciprofloxacin hydrochloride and serratiopeptidase: Pharmaceutical and mechanical analysis.

    PubMed

    Singh, Kushal Pal; Chhabra, Gulshan; Sharma, Vijay; Pathak, Kamla

    2014-01-01

    The aim of the present work was to explore the development of a dual-controlled release periodontal system of a potent broad spectrum first-generation fluoroquinolone, ciprofloxacin, and the anti-inflammatory enzyme serratiopeptidase (STP). Based on 3(2) full factorial design, thermoreversible periodontal sols capable of controlled dual delivery of ciprofloxacin hydrochloride and STP were designed using pluronic F127 and carbopol 934P as thermosensitive gelling polymers. Sol gel transition characteristics, %cumulative drug release at 48(th) h and exvivo mucoadhesive strength were designated as dependent responses. The sols were mucoadhesive, syringeable, and inverted into gels at simulated periodontal cavity temperature. F9 with optimal drug release was identified as the best formulation. Extra design check point generated using Design Expert software 8.02 (Stat-Ease, USA) validated the experimental design. Textural analysis revealed that the developed sols were syringeable and spreadable enough for periodontal treatment so it can be expected that hardness and compressibility of sols would pose no problem during clinical application. The in vitro release behavior exhibited controlled release of both cipro HCl and STP (>90% release). A dual-controlled release thermoreversible periodontal sol of ciproflaxin and STP was successfully developed. Incorporation of STP as anti-inflammatory agent has the potential of developing a therapeutically efficacious system of cipro HCl for treatment of periodontal inflammatory anaerobic infections.

  13. JAK/STAT signaling by cytokine receptors.

    PubMed

    Liu, K D; Gaffen, S L; Goldsmith, M A

    1998-06-01

    The JAK/STAT pathway is recognized as one of the major mechanisms by which cytokine receptors transduce intracellular signals. This system is regulated at multiple levels, including JAK activation, nuclear trafficking of STAT factors, and negative feedback loops. Gene deletion studies have implicated selected STAT factors as predominant mediators for a limited number of lymphokines. This signaling pathway influences normal cell survival and growth mechanisms and may contribute to oncogenic transformation.

  14. Dominant negative stat3 mutant inhibits interleukin-6-induced Jak-STAT signal transduction.

    PubMed

    Kaptein, A; Paillard, V; Saunders, M

    1996-03-15

    Interleukin-6 (IL-6) induces tyrosine phosphorylation and activation of the latent transcription factor Stat3 in HepG2 cells. Mutation of Stat3 tyrosine 705 to phenylalanine (Y705F) inhibits IL-6-induced tyrosine phosphorylation of this Stat3 mutant in transfected HepG2 cells. In cotransfections of HepG2 cells, the Stat3 mutant Y705F causes a reduction of the tyrosine phosphorylation of wild type Stat3-FLAG. Moreover, Y705F inhibits the action of endogenous Stat3 in cotransfected cells, reducing IL-6 induction of a Stat3-responsive reporter construct. Y705F therefore acts as a dominant negative mutation of Stat3.

  15. 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

  16. Nucleocytoplasmic shuttling of STAT transcription factors.

    PubMed

    Meyer, Thomas; Vinkemeier, Uwe

    2004-12-01

    The signal transducer and activator of transcription (STAT) proteins have initially been described as cytoplasmic proteins that enter the nucleus only after cytokine treatment of cells. Contrary to this assumption, it was demonstrated that STATs are constantly shuttling between nucleus and cytoplasm irrespective of cytokine stimulation. This happens both via carrier-dependent as well as carrier-independent transportation. Moreover, it was also recognized that cytokine stimulation triggers nuclear retention of dimeric STATs, rather than affecting the rate of nuclear import. In summary, it is increasingly being appreciated that STAT nucleocytoplasmic cycling determines the quality of cytokine signaling and also constitutes an important area for microbial intervention.

  17. 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.

  18. 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).

  19. Differential STAT3 signaling in the heart

    PubMed Central

    Zgheib, Carlos; Zouein, Fouad A.; Kurdi, Mazen; Booz, George W.

    2012-01-01

    Multiple lines of evidence suggest that the transcription factor STAT3 is linked to a protective and reparative response in the heart. Thus, increasing duration or intensity of STAT3 activation ought to minimize damage and improve heart function under conditions of stress. Two recent studies using genetic mouse models, however, report findings that appear to refute this proposition. Unfortunately, studies often approach the question of the role of STAT3 in the heart from the perspective that all STAT3 signaling is equivalent, particularly when it comes to signaling by IL-6 type cytokines, which share the gp130 signaling protein. Moreover, STAT3 activation is typically equated with phosphorylation of a critical tyrosine residue. Yet, STAT3 transcriptional behavior is subject to modulation by serine phosphorylation, acetylation, and redox status of the cell. Unphosphorylated STAT3 is implicated in gene induction as well. Thus, how STAT3 is activated and also what other signaling events are occurring at the same time is likely to impact on the outcome ultimately linked to STAT3. Notably STAT3 may serve as a scaffold protein allowing it to interact with other singling pathways. In this context, canonical gp130 cytokine signaling may function to integrate STAT3 signaling with a protective PI3K/AKT signaling network via mutual involvement of JAK tyrosine kinases. Differences in the extent of integration may occur between those cytokines that signal through gp130 homodimers and those through heterodimers of gp130 with a receptor α chain. Signal integration may have importance not only for deciding the particular gene profile linked to STAT3, but for the newly described mitochondrial stabilization role of STAT3 as well. In addition, disruption of integrated gp130-related STAT3 signaling may occur under conditions of oxidative stress, which negatively impacts on JAK catalytic activity. For these reasons, understanding the importance of STAT3 signaling to heart function

  20. Hendra virus V protein inhibits interferon signaling by preventing STAT1 and STAT2 nuclear accumulation.

    PubMed

    Rodriguez, Jason J; Wang, Lin-Fa; Horvath, Curt M

    2003-11-01

    The V protein of the recently emerged paramyxovirus, Nipah virus, has been shown to inhibit interferon (IFN) signal transduction through cytoplasmic sequestration of cellular STAT1 and STAT2 in high-molecular-weight complexes. Here we demonstrate that the closely related Hendra virus V protein also inhibits cellular responses to IFN through binding and cytoplasmic sequestration of both STAT1 and STAT2, but not STAT3. These findings demonstrate a V protein-mediated IFN signal evasion mechanism that is a general property of the known Henipavirus species.

  1. Dust Devil - Sol 25

    NASA Image and Video Library

    1997-08-15

    This figure shows the signature of a dust devil that passed over the Pathfinder Lander on Sol 25. Since then we have seen several similar features. The black line shows surface pressure plotted over a period of approximately two minutes. The sharp minimum approximately 0.5% below the background pressure is very clear. The dashed curves show raw data from two hot wire wind sensor elements (Blue = Wind Sensor 4 = East Wind, Red = Wind Sensor 1 = West Wind). When the wind blows directly on an element it cools. It is clear from the figure that the East wind increases suddenly as the dust devil approaches the lander and the pressure begins to fall. As the dust devil passes over the lander, pressure begins to rise, the East wind dies away and the West wind increases suddenly. Finally as the dust devil moves away, pressure returns to normal and the West wind dies away. This is a textbook dust-devil signature. http://photojournal.jpl.nasa.gov/catalog/PIA00900

  2. Design of Conditionally Active STATs: Insights into STAT Activation and Gene Regulatory Function

    PubMed Central

    Milocco, Lawrence H.; Haslam, Jennifer A.; Rosen, Jonathan; Seidel, H. Martin

    1999-01-01

    The STAT (signal transducer and activator of transcription) signaling pathway is activated by a large number of cytokines and growth factors. We sought to design a conditionally active STAT that could not only provide insight into basic questions about STAT function but also serve as a powerful tool to determine the precise biological role of STATs. To this end, we have developed a conditionally active STAT by fusing STATs with the ligand-binding domain of the estrogen receptor (ER). We have demonstrated that the resulting STAT-ER chimeras are estrogen-inducible transcription factors that retain the functional and biochemical characteristics of the cognate wild-type STATs. In addition, these tools have allowed us to evaluate separately the contribution of tyrosine phosphorylation and dimerization to STAT function. We have for the first time provided experimental data supporting the model that the only apparent role of STAT tyrosine phosphorylation is to drive dimerization, as dimerization alone is sufficient to unmask a latent STAT nuclear localization sequence and induce nuclear translocation, sequence-specific DNA binding, and transcriptional activity. PMID:10082558

  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. 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.

  5. STAT subtype specificity and ischemic preconditioning in mice: is STAT-3 enough?

    PubMed Central

    Goodman, Michael D.; Koch, Sheryl E.; Afzal, Muhammad R.

    2011-01-01

    The role of other STAT subtypes in conferring ischemic tolerance is unclear. We hypothesized that in STAT-3 deletion alternative STAT subtypes would protect myocardial function against ischemia-reperfusion injury. Wild-type (WT) male C57BL/6 mice or mice with cardiomyocyte STAT-3 knockout (KO) underwent baseline echocardiography. Langendorff-perfused hearts underwent ischemic preconditioning (IPC) or no IPC before ischemia-reperfusion. Following ex vivo perfusion, hearts were analyzed for STAT-5 and -6 phosphorylation by Western blot analysis of nuclear fractions. Echocardiography and postequilibration cardiac performance revealed no differences in cardiac function between WT and KO hearts. Phosphorylated STAT-5 and -6 expression was similar in WT and KO hearts before perfusion. Contractile function in WT and KO hearts was significantly impaired following ischemia-reperfusion in the absence of IPC. In WT hearts, IPC significantly improved the recovery of the maximum first derivative of developed pressure (+dP/dtmax) compared with that in hearts without IPC. IPC more effectively improved end-reperfusion dP/dtmax in WT hearts compared with KO hearts. Preconditioned and nonpreconditioned KO hearts exhibited increased phosphorylated STAT-5 and -6 expression compared with WT hearts. The increased subtype activation did not improve the efficacy of IPC in KO hearts. In conclusion, baseline cardiac performance is preserved in hearts with cardiac-restricted STAT-3 deletion. STAT-3 deletion attenuates preconditioning and is not associated with a compensatory upregulation of STAT-5 and -6 subtypes. The activation of STAT-5 and -6 in KO hearts following ischemic challenge does not provide functional compensation for the loss of STAT-3. JAK-STAT signaling via STAT-3 is essential for effective IPC. PMID:21131482

  6. 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

  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. STATs: An Old Story, Yet Mesmerizing

    PubMed Central

    Abroun, Saeid; Saki, Najmaldin; Ahmadvand, Mohammad; Asghari, Farahnaz; Salari, Fatemeh; Rahim, Fakher

    2015-01-01

    Signal transducers and activators of transcription (STATs) are cytoplasmic transcription factors that have a key role in cell fate. STATs, a protein family comprised of seven members, are proteins which are latent cytoplasmic transcription factors that convey signals from the cell surface to the nucleus through activation by cytokines and growth factors. The signaling pathways have diverse biological functions that include roles in cell differentiation, proliferation, development, apoptosis, and inflammation which place them at the center of a very active area of research. In this review we explain Janus kinase (JAK)/STAT signaling and focus on STAT3, which is transient from cytoplasm to nucleus after phosphorylation. This procedure controls fundamental biological processes by regulating nuclear genes controlling cell proliferation, survival, and development. In some hematopoietic disorders and cancers, overexpression and activation of STAT3 result in high proliferation, suppression of cell differentiation and inhibition of cell maturation. This article focuses on STAT3 and its role in malignancy, in addition to the role of microRNAs (miRNAs) on STAT3 activation in certain cancers. PMID:26464811

  9. STATs: An Old Story, Yet Mesmerizing.

    PubMed

    Abroun, Saeid; Saki, Najmaldin; Ahmadvand, Mohammad; Asghari, Farahnaz; Salari, Fatemeh; Rahim, Fakher

    2015-01-01

    Signal transducers and activators of transcription (STATs) are cytoplasmic transcription factors that have a key role in cell fate. STATs, a protein family comprised of seven members, are proteins which are latent cytoplasmic transcription factors that convey signals from the cell surface to the nucleus through activation by cytokines and growth factors. The signaling pathways have diverse biological functions that include roles in cell differentiation, proliferation, development, apoptosis, and inflammation which place them at the center of a very active area of research. In this review we explain Janus kinase (JAK)/STAT signaling and focus on STAT3, which is transient from cytoplasm to nucleus after phosphorylation. This procedure controls fundamental biological processes by regulating nuclear genes controlling cell proliferation, survival, and development. In some hematopoietic disorders and cancers, overexpression and activation of STAT3 result in high proliferation, suppression of cell differentiation and inhibition of cell maturation. This article focuses on STAT3 and its role in malignancy, in addition to the role of microRNAs (miRNAs) on STAT3 activation in certain cancers.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Accelerated purification of colloidal silica sols

    NASA Technical Reports Server (NTRS)

    Bahnsen, E. B.; Garofalini, S.; Pechman, A.

    1979-01-01

    Accelerated purification process for colloidal sols using heat/deionization scheme, sharply reduces waiting time between deionization cycles from several months to a few days. Process produces same high purity silica sols as conventional methods.

  19. Increased phosphorylation of STAT5b, but not STAT5a, in nasal polyps.

    PubMed

    Linke, Robert; Pries, Ralph; Könnecke, Michael; Bruchhage, Karl-Ludwig; Böscke, Robert; Gebhard, Maximilian; Wollenberg, Barbara

    2015-01-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a recurrent, benign, extensively proliferating disease that is triggered by inflammation. The signaling pathways in sinusitis and the regulation by intracellular signaling peptides and proteins are not fully understood. Signal transducer and activator of transcription (STAT) 5a and STAT5b are two closely related phosphokinases involved in the regulation of diverse cellular functions, including proliferation and apoptosis. The objective of the study was to investigate the expression, activation, and distribution of STAT5 Transcription factor in CRSwNP. We studied these transcription factors in tissue samples of nasal polyps and inferior turbinates from a total of 35 patients with CRSwNP and compared them with healthy nasal mucosa. The samples were analyzed by using a DNA microarray, quantitative real-time polymerase chain reaction, a protein array, immunoblot, immunoprecipitation and immunohistochemistry. We found equivalent overall expression of STAT5a in all tissue types. We observed an increase in the expression of STAT5b protein in both polyps and turbinates of patients with CRSwNP. In addition, STAT5b, but not STAT5a, was activated by phosphorylation in nasal polyps. Phosphorylated STAT5a/b was not detectable in the epithelium of turbinates from either patients with CRSwNP or patients with healthy mucosa, but it was clearly expressed in the epithelium of nasal polyps. Analysis of these data indicates distinct expression and activation of STAT5a and STAT5b in nasal polyps, particularly the activation of STAT5b. It is possible that STAT5b may contribute to the development of nasal polyps.

  20. Inhibition of Stat1-mediated gene activation by PIAS1

    PubMed Central

    Liu, Bin; Liao, Jiayu; Rao, Xiaoping; Kushner, Steven A.; Chung, Chan D.; Chang, David D.; Shuai, Ke

    1998-01-01

    STAT (signal transducer and activator of transcription) proteins are latent cytoplasmic transcription factors that become activated by tyrosine phosphorylation in response to cytokine stimulation. Tyrosine phosphorylated STATs dimerize and translocate into the nucleus to activate specific genes. Different members of the STAT protein family have distinct functions in cytokine signaling. Biochemical and genetic analysis has demonstrated that Stat1 is essential for gene activation in response to interferon stimulation. Although progress has been made toward understanding STAT activation, little is known about how STAT signals are down-regulated. We report here the isolation of a family of PIAS (protein inhibitor of activated STAT) proteins. PIAS1, but not other PIAS proteins, blocked the DNA binding activity of Stat1 and inhibited Stat1-mediated gene activation in response to interferon. Coimmunoprecipitation analysis showed that PIAS1 was associated with Stat1 but not Stat2 or Stat3 after ligand stimulation. The in vivo PIAS1–Stat1 interaction requires phosphorylation of Stat1 on Tyr-701. These results identify PIAS1 as a specific inhibitor of Stat1-mediated gene activation and suggest that there may exist a specific PIAS inhibitor in every STAT signaling pathway. PMID:9724754

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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)

  10. 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)

  11. 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.

  12. Cloning of human Stat5B. Reconstitution of interleukin-2-induced Stat5A and Stat5B DNA binding activity in COS-7 cells.

    PubMed

    Lin, J X; Mietz, J; Modi, W S; John, S; Leonard, W J

    1996-05-03

    We have isolated a second human Stat5 cDNA, Stat5B, and demonstrated that the genes encoding both Stat5A and Stat5B are located at chromosome 17q11.2. Both genes were constitutively transcribed in peripheral blood lymphocytes. By using specific antisera, we demonstrated that both Stat5A and Stat5B are activated by interleukin-2 (IL-2) in peripheral blood lymphocytes, natural killer-like YT leukemia cells, and human T cell lymphotropic virus type I-transformed MT-2 T cells. In COS-7 cells, which constitutively express the Janus family tyrosine kinase Jak1, reconstitution of IL-2-induced Stat5A and Stat5B DNA binding activities was dependent on the coexpression of Jak3 along with the IL-2 receptor beta chain and the common cytokine receptor gamma-chain. This IL-2-induced Stat5 activation was dependent on the presence of either of two tyrosines (Tyr-392 or Tyr-510) in the IL-2 receptor beta chain, indicating that either of these two tyrosines can serve as a docking site. Moreover, we demonstrated that human Stat5 activation is also dependent on Tyr-694 in Stat5A and Tyr-699 in Stat5B, indicating that these tyrosines are required for dimerization. The COS-7 reconstitution system described herein provides a valuable assay for further elucidation of the IL-2-activated JAK-STAT pathway.

  13. 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

  14. 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.

  15. Weapons of STAT destruction. Interferon evasion by paramyxovirus V protein.

    PubMed

    Horvath, Curt M

    2004-12-01

    The signal transducer and activator of transcription (STAT) family of proteins function to activate gene transcription downstream of myriad cytokine and growth factor signals. The prototype STAT proteins, STAT1 and STAT2, are required for innate and adaptive antimicrobial immune responses that result from interferon signal transduction. While many viruses have evolved the ability to avoid these antiviral cytokines, the Paramyxoviruses are distinct in their abilities to interfere directly with STAT proteins. Individual paramyxovirus species differ greatly in their precise mechanism of STAT signaling evasion, but a virus-encoded protein called V plays a central role in this process. The theme of V-dependent interferon evasion and its variations provide significant insights into virus-host interactions and viral immune evasion that can help define targets for antiviral drug design. Exposure of the viral weapons of STAT destruction may also be instructive for application to STAT-directed therapeutics for diseases characterized by STAT hyperactivity.

  16. 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.

  17. 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)].

  18. HIS-TORIC: extending core ICRF wave simulation to include realistic SOL plasmas

    NASA Astrophysics Data System (ADS)

    Shiraiwa, S.; Wright, J. C.; Lee, J. P.; Bonoli, P. T.

    2017-08-01

    This paper presents a novel approach to incorporating an arbitrarily shaped edge scrape-off-layer (SOL) plasma and an ion cyclotron range of frequency (ICRF) antenna structure into existing core ICRF wave simulation models. We partition the entire computation domain into two sub-domains: a core and an edge region. Simulations in each domain are performed separately with appropriate numerical solvers. For the core, the TORIC ICRF solver (Brambilla 1999 Plasma Phys. Control. Fusion 41 1) was modified to impose an essential (Dirichlet) boundary condition at its interface with the edge domain. In the edge, a finite element method is used to solve a cold collisional plasma model. The domains are then joined together using the continuity boundary condition for the tangential electric and magnetic fields at their interfaces (Hybrid Integration of SOL to TORIC: HIS-TORIC). The model developed here was tested using an ICRH H minority heating scenario on the Alcator C-Mod tokamak (Hutchinson et al 1994 Phys. Plasmas 1 1511). The simulated pattern of core wave propagation agrees well with a standard TORIC simulation. This approach opens the possibility of using a realistic diverted SOL plasma and a complicated 3D RF antenna together with a rigorous hot core plasma model, while requiring only minimal modification to existing RF codes.

  19. 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.

  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. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Structural Tailoring of Advanced Turboprops (STAT)

    NASA Technical Reports Server (NTRS)

    Brown, Kenneth W.

    1988-01-01

    This interim report describes the progress achieved in the structural Tailoring of Advanced Turboprops (STAT) 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. This report provides a detailed description of the input, optimization procedures, approximate analyses and refined analyses, as well as validation test cases for the STAT program. In addition, conclusions and recommendations are summarized.

  8. 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.

  9. Mitochondrial Stat3, the Need for Design Thinking.

    PubMed

    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 Ca(2+) 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. Dual controlled release, in situ gelling periodontal sol of metronidazole benzoate and serratiopeptidase: statistical optimization and mechanistic evaluation.

    PubMed

    Kumari, Neeraj; Pathak, Kamla

    2012-01-01

    In situ gelling syringeable periodontal sol capable of dual controlled delivery of metronidazole benzoate and serratiopeptidase was designed based on 2(3) factorial design with drug, poloxamer 407 and aerosil as independent variables and sol gel transition characteristics, %CDR(48h) and palatability as responses. The sols had agreeable taste, were mucoadhesive, syringeable and inverted into gels at periodontal cavity temperature. F8 with optimal drug release was identified as the best formulation. The dispersion characteristics of poloxamer significantly affected the pharmacotechnical properties of the in situ gelling systems. Extra design checkpoint generated using Design Expert software 8.02 (Stat-Ease, USA) validated the experimental design. Thus a thermoreversible, in situ gelling and syringeable periodontal sol with acceptable taste characteristics that offered controlled release of metronidazole benzoate and serratiopeptidase was developed for application into the periodontal pocket. The developed optimized sol was satisfactory in terms of taste, syringeability, palatability and incorporation of serratiopeptidase as anti-inflammatory agent, has the potential of developing a therapeutically efficacious system for treatment of periodontal inflammatory anaerobic infections.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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…

  2. Evaluation of the Special Tertiary Admissions Test (STAT)

    ERIC Educational Resources Information Center

    Coates, Hamish; Friedman, Tim

    2010-01-01

    This paper reports findings from the first national Australian study of the predictive validity of the Special Tertiary Admissions Test (STAT). Background on tertiary admissions procedures in Australia is presented, followed by information on STAT and the research methods. The results affirm that STAT, through the provision of baseline and…

  3. 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

  4. 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…

  5. The interpretation of dielectric spectroscopy measurements on silica and hematite sols.

    PubMed

    Chassagne, C; Bedeaux, D; Koper, G J M

    2002-11-01

    Experimental data on the dielectric response of silica and hematite sols from the literature are interpreted using an analytical theory developed previously (Chassagne, C., Bedeaux, D., and Koper, G. J. M., J. Phys. Chem B105, 11,743 (2001), and Physica A, to be published). The theory is found to correctly predict both the relaxation frequency and the dielectric permittivity enhancement at low frequencies with only one free parameter. This parameter can be the zeta potential or the Stern layer conductance, in the case that the zeta potential is fixed to agree with the electrophoretic mobility measurements.

  6. 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.

  7. 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.

  8. Spirit Traverse Map, Sol 404

    NASA Image and Video Library

    2005-02-26

    NASA's Mars Exploration Rover Spirit drove a total of 4,143 meters (2.57 miles) between its landing in January 2004 and its 404th martian day, or sol (Feb. 20, 2005). This map on an image taken by the Mars Orbiter Camera on NASA's Mars Global Surveyor shows the course the rover drove during that time. The rover has recently been approaching a ridge overlooking "Tennessee Valley" on the north flank of "Husband Hill." http://photojournal.jpl.nasa.gov/catalog/PIA07393

  9. Spirit's View on Sol 107

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This cylindrical-projection mosaic was assembled from images taken by the navigation camera on the Mars Exploration Rover Spirit on sol 107 (April 21, 2004) at a region dubbed 'site 32.' Spirit is sitting east of 'Missoula Crater,' no longer in the crater's ejecta field, but on outer plains. Since landing, Spirit has traveled almost exclusively over ejecta fields. This new landscape looks different with fewer angular rocks and more rounded, vesicle-filled rocks. Spirit will continue another 1,900 meters (1.18 miles) along this terrain before reaching the western base of the 'Columbia Hills.'

  10. Erratum: Galilean invariance at quantum Hall edge [Phys. Rev. B 91, 195409 (2015)

    NASA Astrophysics Data System (ADS)

    Moroz, Sergej; Hoyos, Carlos; Radzihovsky, Leo

    2017-07-01

    Motivated by a recent Comment by Höller and Read [Phys. Rev. B 93, 197401 (2016)], 10.1103/PhysRevB.93.197401, we revisit the problem of a chiral Luttinger liquid on a boundary of a Galilean-invariant quantum Hall fluid. After correcting the linear-response calculation, the real part of the longitudinal conductivity derived in the model constructed in our paper agrees with the result found in the Comment for noninteracting fermions confined by a linear potential. We also withdraw our previous conjecture that the longitudinal conductivity contains a universal contribution determined by the "shift" and provide arguments demonstrating its nonuniversal nature.

  11. Comment on “Piezonuclear decay of thorium” [Phys. Lett. A 373 (2009) 1956

    NASA Astrophysics Data System (ADS)

    Kowalski, L.

    2010-01-01

    Cardone et al. [F. Cardone, R. Mignani, A. Petrucci, Phys. Lett. A 373 (2009) 1956] claim that cavitation speeds up radioactive decay of 228Th dissolved in water. The experimental evidence they presented was criticized by Ericsson et al. [G. Ericsson, S. Pomp, H. Sjöstrand, E. Traneus, Phys. Lett. A 373 (2009) 3795]. This Comment focuses on a presumably-ignored trivial effect that might be responsible for the reported experimental results. It also contains suggestions for improving the quality of future investigations.

  12. 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.

  13. 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

  14. Role of Jak kinases and STATs in cytokine signal transduction.

    PubMed

    Leonard, W J

    2001-04-01

    The Janus family tyrosine kinase-signal transducer and activator of transcription (Jak-STAT) signaling pathway is broadly used by interferons and type I cytokines. These cytokines and interferons activate Janus family tyrosine kinases (Jak kinases), which in turn phosphorylate and thereby activate STAT proteins. Before activation, STAT proteins are cytosolic proteins; after activation, however, they are translocated to the nucleus where they function as transcription factors. This review summarizes salient features of the Jak-STAT pathway and focuses on the functional role of the different Jak kinases and STATs in vivo.

  15. 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.

  16. 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.

  17. 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.

  18. Comment on ``Quantum key distribution without alternative measurements'' [Phys. Rev. A 61, 052312 (2000)

    NASA Astrophysics Data System (ADS)

    Zhang, Yong-Sheng; Li, Chuan-Feng; Guo, Guang-Can

    2001-03-01

    In a recent paper [A. Cabello, Phys. Rev. A 61, 052312 (2000)], a quantum key distribution protocol based on entanglement swapping was proposed. However, in this Comment, it is shown that this protocol is insecure if Eve uses a special strategy to attack.

  19. Non-canonical Stat3 signaling in cancer.

    PubMed

    Srivastava, Jaya; DiGiovanni, John

    2016-12-01

    Stat3 is a member of the signal transducers and activators of transcription family and is a known regulator of essential biologic processes including angiogenesis, apoptosis, cell cycle progression, and cell migration. Canonical Stat3-mediated signaling involves tyrosine phosphorylation on specific residues that leads to homodimerization and translocation to the nucleus. For many years it was presumed that most, if not all, of the functions of Stat3, both normal and aberrant, were due to the canonical cytokine and growth factor signaling mechanisms. Recent studies suggest that Stat3 functions through alternate non-canonical pathways to bring about some of these biological functions both in normal cells as well as during cancer development and progression. A number of studies have now shown that Stat3 has a function in mitochondria and that unphosphorylated Stat3 (uStat3) can also function as a transcription factor broadening the potential mechanisms involved in Stat3 action. In this review article, we discuss these two main non-canonical functions of Stat3 and their potential roles in oncogenesis. Given the many facets of Stat3 signaling, additional comprehensive investigations are required to fully understand the role of non-canonical Stat3 signaling in cancer and whether these pathways can be targeted for cancer prevention and treatment. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  20. Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas

    PubMed Central

    Pilati, Camilla; Amessou, Mohamed; Bihl, Michel P.; Balabaud, Charles; Van Nhieu, Jeanne Tran; Paradis, Valérie; Nault, Jean Charles; Izard, Tina; Bioulac-Sage, Paulette; Couchy, Gabrielle; Poussin, Karine

    2011-01-01

    Inflammatory hepatocellular adenomas (IHCAs) are benign liver tumors. 60% of these tumors have IL-6 signal transducer (IL6ST; gp130) mutations that activate interleukin 6 (IL-6) signaling. Here, we report that 12% of IHCA subsets lacking IL6ST mutations harbor somatic signal transducer and activator of transcription 3 (STAT3) mutations (6/49). Most of these mutations are amino acid substitutions in the SH2 domain that directs STAT3 dimerization. In contrast to wild-type STAT3, IHCA STAT3 mutants constitutively activated the IL-6 signaling pathway independent of ligand in hepatocellular cells. Indeed, the IHCA STAT3 Y640 mutant homodimerized independent of IL-6 and was hypersensitive to IL-6 stimulation. This was associated with phosphorylation of tyrosine 705, a residue required for IL-6–induced STAT3 activation. Silencing or inhibiting the tyrosine kinases JAK1 or Src, which phosphorylate STAT3, impaired constitutive activity of IHCA STAT3 mutants in hepatocellular cells. Thus, we identified for the first time somatic STAT3 mutations in human tumors, revealing a new mechanism of recurrent STAT3 activation and underscoring the role of the IL-6–STAT3 pathway in benign hepatocellular tumorigenesis. PMID:21690253

  1. 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.

  2. 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

  3. iNuc-PhysChem: A Sequence-Based Predictor for Identifying Nucleosomes via Physicochemical Properties

    PubMed Central

    Feng, Peng-Mian; Ding, Chen; Zuo, Yong-Chun; Chou, Kuo-Chen

    2012-01-01

    Nucleosome positioning has important roles in key cellular processes. Although intensive efforts have been made in this area, the rules defining nucleosome positioning is still elusive and debated. In this study, we carried out a systematic comparison among the profiles of twelve DNA physicochemical features between the nucleosomal and linker sequences in the Saccharomyces cerevisiae genome. We found that nucleosomal sequences have some position-specific physicochemical features, which can be used for in-depth studying nucleosomes. Meanwhile, a new predictor, called iNuc-PhysChem, was developed for identification of nucleosomal sequences by incorporating these physicochemical properties into a 1788-D (dimensional) feature vector, which was further reduced to a 884-D vector via the IFS (incremental feature selection) procedure to optimize the feature set. It was observed by a cross-validation test on a benchmark dataset that the overall success rate achieved by iNuc-PhysChem was over 96% in identifying nucleosomal or linker sequences. As a web-server, iNuc-PhysChem is freely accessible to the public at http://lin.uestc.edu.cn/server/iNuc-PhysChem. For the convenience of the vast majority of experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated mathematics that were presented just for the integrity in developing the predictor. Meanwhile, for those who prefer to run predictions in their own computers, the predictor's code can be easily downloaded from the web-server. It is anticipated that iNuc-PhysChem may become a useful high throughput tool for both basic research and drug design. PMID:23144709

  4. Nuclear relocation of STAT6 reliably predicts NAB2-STAT6 fusion for the diagnosis of solitary fibrous tumour.

    PubMed

    Koelsche, Christian; Schweizer, Leonille; Renner, Marcus; Warth, Arne; Jones, David T W; Sahm, Felix; Reuss, David E; Capper, David; Knösel, Thomas; Schulz, Birte; Petersen, Iver; Ulrich, Alexis; Renker, Eva Kristin; Lehner, Burkhard; Pfister, Stefan M; Schirmacher, Peter; von Deimling, Andreas; Mechtersheimer, Gunhild

    2014-11-01

    Nuclear relocation of STAT6 has been shown in tumours with NAB2-STAT6 fusion, and has been proposed as an ancillary marker for the diagnosis of solitary fibrous tumours (SFTs). The aim of this study was to verify the utility of STAT6 immunohistology in diagnosing SFT. A total of 689 formalin-fixed paraffin-embedded tumours comprising 35 pleural SFTs and 654 other mesenchymal tumours were investigated for STAT6 expression using immunohistochemistry. Nine dedifferentiated liposarcomas (DDLSs) and five SFTs were also examined for the presence of NAB2-STAT6 fusion at the protein level using the proximity ligation assay (PLA), and for copy number variants (CNVs) with the Illumina Infinium Human Methylation450 array. Thirty-four of 35 SFTs showed strong nuclear STAT6 expression. Furthermore, five of 68 DDLSs, two of 130 undifferentiated pleomorphic sarcomas and one of 63 cases of nodular fasciitis showed moderate to strong nuclear STAT6 expression. The PLA indicated the presence of NAB2-STAT6 fusion protein in SFTs, but signal was also detected in some DDLSs. Copy number analysis showed an overall low frequency of chromosomal imbalances in SFTs, but complex karyotypes in DDLSs, including amplification of STAT6 and MDM2 loci. The detection of nuclear relocation of STAT6 with immunohistochemistry is a characteristic of SFTs, and may serve as a diagnostic marker that indicates NAB2-STAT6 fusion and helps to discriminate SFTs from histological mimics. © 2014 John Wiley & Sons Ltd.

  5. Nipah virus V protein evades alpha and gamma interferons by preventing STAT1 and STAT2 activation and nuclear accumulation.

    PubMed

    Rodriguez, Jason J; Parisien, Jean-Patrick; Horvath, Curt M

    2002-11-01

    Characterization of recent outbreaks of fatal encephalitis in southeast Asia identified the causative agent to be a previously unrecognized enveloped negative-strand RNA virus of the Paramyxoviridae family, Nipah virus. One feature linking Nipah virus to this family is a conserved cysteine-rich domain that is the hallmark of paramyxovirus V proteins. The V proteins of other paramyxovirus species have been linked with evasion of host cell interferon (IFN) signal transduction and subsequent antiviral responses by inducing proteasomal degradation of the IFN-responsive transcription factors, STAT1 or STAT2. Here we demonstrate that Nipah virus V protein escapes IFN by a distinct mechanism involving direct inhibition of STAT protein function. Nipah virus V protein differs from other paramyxovirus V proteins in its subcellular distribution but not in its ability to inhibit cellular IFN responses. Nipah virus V protein does not induce STAT degradation but instead inhibits IFN responses by forming high-molecular-weight complexes with both STAT1 and STAT2. We demonstrate that Nipah virus V protein accumulates in the cytoplasm by a Crm1-dependent mechanism, alters the STAT protein subcellular distribution in the steady state, and prevents IFN-stimulated STAT redistribution. Consistent with the formation of complexes, STAT protein tyrosine phosphorylation is inhibited in cells expressing the Nipah virus V protein. As a result, Nipah virus V protein efficiently prevents STAT1 and STAT2 nuclear translocation in response to IFN, inhibiting cellular responses to both IFN-alpha and IFN-gamma.

  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. Reply to “Comment on ‘Piezonuclear decay of thorium’ [Phys. Lett. A 373 (2009) 1956]” [Phys. Lett. A 374 (2009) 696

    NASA Astrophysics Data System (ADS)

    Cardone, Fabio; Mignani, Roberto; Petrucci, Andrea

    2010-01-01

    In a Letter appearing in this issue of Physics Letters A, Kowalski raises some critical comments on the experiment [F. Cardone, R. Mignani, A. Petrucci, Phys. Lett. A 373 (2009) 1956] that we carried out by cavitating a solution of Thorium-228. The experiment highlighted the anomalous decay of Thorium, thus confirming the results previously obtained by Urutskoev et al. by explosion of titanium foils in solutions. In this Letter, we reply to these comments. We agree with Kowalski that critical comments are one of the key factors of the process to improve the quality of experiments and the interpretation of results. However we do hope that these comments together with the details provided in the replies will promote further and better experiments which are certainly worth performing in order to shed a brighter light on this issue, as Kowalski himself suggests in his comment.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. Reply to: “Comment on: ‘Exposed-key weakness of αη’ [Phys. Lett. A 370 (2007) 131]” [Phys. Lett. A 372 (2008) 7091

    NASA Astrophysics Data System (ADS)

    Ahn, Charlene; Birnbaum, Kevin

    2008-11-01

    We present simulations countering the claims in [R. Nair, H.P. Yuen, Phys. Lett. A 372 (2008) 7091] that the approximation given in [C. Ahn, K. Birnbaum, Phys. Lett. A 370 (2007) 131, quant-ph/0612058] for the eavesdropper's entropy on the encrypted key cannot be valid, and additionally discuss ways in which our views on security requirements differ from those given in [R. Nair, H.P. Yuen, Phys. Lett. A 372 (2008) 7091].

  13. 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.

  14. 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

  15. STAT1 from the cell membrane to the DNA

    PubMed Central

    Lillemeier, Björn F.; Köster, Mario; Kerr, Ian M.

    2001-01-01

    The binding of interferons (IFNs) to their receptors leads to the phosphorylation and activation of signal transducers and activators of transcription (STATs), and their translocation from the cytoplasm to the nucleus. The mechanisms by which the STATs move to the nuclear pore are not, however, known. Here it is shown that IFN-α and -γ signalling and STAT1 translocation are independent of the actin cytoskeleton or microtubules. Using fluorescence loss in photobleaching (FLIP) and fluorescence recovery after photobleaching (FRAP) experiments, the mobility of a fusion protein of STAT1 with green fluorescent protein (STAT1–GFP) was compared with that of GFP and protein kinase C–GFP. In IFN-γ-treated and control cells, cytoplasmic STAT1–GFP shows high, energy-independent, mobility comparable to that of freely diffusible GFP. A random walk model for movement of STAT1 from the plasma membrane to the nuclear pore is, therefore, indicated. Nuclear STAT1–GFP showed similar high mobility, with exclusion from nucleoli, consistent with high rates of association and dissociation of STAT1–DNA and/or STAT1–protein complexes in the nucleoplasm of the cell. PMID:11350940

  16. Intermolecular disulfide bond influences unphosphorylated STAT3 dimerization and function.

    PubMed

    Butturini, Elena; Gotte, Giovanni; Dell'Orco, Daniele; Chiavegato, Giulia; Marino, Valerio; Canetti, Diana; Cozzolino, Flora; Monti, Maria; Pucci, Piero; Mariotto, Sofia

    2016-10-01

    Signal transducer and activator of transcription 3 (STAT3) is a transcription factor activated by the phosphorylation of tyrosine 705 in response to many cytokines and growth factors. Recently, the roles for unphosphorylated STAT3 (U-STAT3) have been described in response to cytokine stimulation, in cancers, and in the maintenance of heterochromatin stability. It has been reported that U-STAT3 dimerizes, shuttles between the cytoplasm and nucleus, and binds to DNA, thereby driving genes transcription. Although many reports describe the active role of U-STAT3 in oncogenesis in addition to phosphorylated STAT3, the U-STAT3 functional pathway remains elusive.In this report, we describe the molecular mechanism of U-STAT3 dimerization, and we identify the presence of two intermolecular disulfide bridges between Cys367 and Cys542 and Cys418 and Cys426, respectively. Recently, we reported that the same cysteines contribute to the redox regulation of STAT3 signaling pathway both in vitro and in vivo The presence of these disulfides is here demonstrated to largely contribute to the structure and the stability of U-STAT3 dimer as the dimeric form rapidly dissociates upon reduction in the S-S bonds. In particular, the Cys367-Cys542 disulfide bridge is shown to be critical for U-STAT3 DNA-binding activity. Mutation of the two Cys residues completely abolishes the DNA-binding capability of U-STAT3. Spectroscopic investigations confirm that the noncovalent interactions are sufficient for proper folding and dimer formation, but that the interchain disulfide bonds are crucial to preserve the functional dimer. Finally, we propose a reaction scheme of U-STAT3 dimerization with a first common step followed by stabilization through the formation of interchain disulfide bonds. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  17. JAK/Stat signaling regulates heart precursor diversification in Drosophila.

    PubMed

    Johnson, Aaron N; Mokalled, Mayssa H; Haden, Tom N; Olson, Eric N

    2011-11-01

    Intercellular signal transduction pathways regulate the NK-2 family of transcription factors in a conserved gene regulatory network that directs cardiogenesis in both flies and mammals. The Drosophila NK-2 protein Tinman (Tin) was recently shown to regulate Stat92E, the Janus kinase (JAK) and Signal transducer and activator of transcription (Stat) pathway effector, in the developing mesoderm. To understand whether the JAK/Stat pathway also regulates cardiogenesis, we performed a systematic characterization of JAK/Stat signaling during mesoderm development. Drosophila embryos with mutations in the JAK/Stat ligand upd or in Stat92E have non-functional hearts with luminal defects and inappropriate cell aggregations. Using strong Stat92E loss-of-function alleles, we show that the JAK/Stat pathway regulates tin expression prior to heart precursor cell diversification. tin expression can be subdivided into four phases and, in Stat92E mutant embryos, the broad phase 2 expression pattern in the dorsal mesoderm does not restrict to the constrained phase 3 pattern. These embryos also have an expanded pericardial cell domain. We show the E(spl)-C gene HLHm5 is expressed in a pattern complementary to tin during phase 3 and that this expression is JAK/Stat dependent. In addition, E(spl)-C mutant embryos phenocopy the cardiac defects of Stat92E embryos. Mechanistically, JAK/Stat signals activate E(spl)-C genes to restrict Tin expression and the subsequent expression of the T-box transcription factor H15 to direct heart precursor diversification. This study is the first to characterize a role for the JAK/Stat pathway during cardiogenesis and identifies an autoregulatory circuit in which tin limits its own expression domain.

  18. SolTrace Optical Analysis Software

    SciTech Connect

    Wendelin, Tim; Dobos, Aron; Lewandowski, Allan

    2001-12-31

    SolTrace is a software package that models solar power optical systems and analyzes their performance. SolTrace can model parabolic trough collectors, point-focus concentrating systems, and power towers. It rapidly displays and saves data as scatter plots, flux maps, and performance graphs. SolTrace can model optical geometry as a series of stages, composed of optical elements that possess attributes such as shape, contour, and optical quality. It can also model any number of stages containing any number of different elements, and it features an extensive variety of available shapes and contours.

  19. Opportunity View on Sol 397 (vertical)

    NASA Image and Video Library

    2005-03-17

    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 397th martian day, or sol, of its surface mission (March 6, 2005). Opportunity had completed a drive of 124 meters (407 feet) across the rippled flatland of the Meridiani Planum region on the previous sol, but did not drive on this sol. This location is catalogued as Opportunity's site 48. The view is presented here as a vertical projection with geometric and brightness seam correction. http://photojournal.jpl.nasa.gov/catalog/PIA07463

  20. 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.

  1. 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.

  2. 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.

  3. Porcine Reproductive and Respiratory Syndrome Virus Antagonizes JAK/STAT3 Signaling via nsp5, Which Induces STAT3 Degradation.

    PubMed

    Yang, Liping; Wang, Rong; Ma, Zexu; Xiao, Yueqiang; Nan, Yuchen; Wang, Yu; Lin, Shaoli; Zhang, Yan-Jin

    2017-02-01

    Signal transducer and activator of transcription 3 (STAT3) is a pleiotropic signaling mediator of many cytokines, including interleukin-6 (IL-6) and IL-10. STAT3 is known to play critical roles in cell growth, proliferation, differentiation, immunity and inflammatory responses. The objective of this study was to determine the effect of porcine reproductive and respiratory syndrome virus (PRRSV) infection on the STAT3 signaling since PRRSV induces a weak protective immune response in host animals. We report here that PRRSV infection of MARC-145 cells and primary porcine pulmonary alveolar macrophages led to significant reduction of STAT3 protein level. Several strains of both PRRSV type 1 and type 2 led to a similar reduction of STAT3 protein level but had a minimal effect on its transcripts. The PRRSV-mediated STAT3 reduction was in a dose-dependent manner as the STAT3 level decreased, along with incremental amounts of PRRSV inocula. Further study showed that nonstructural protein 5 (nsp5) of PRRSV induced the STAT3 degradation by increasing its polyubiquitination level and shortening its half-life from 24 h to ∼3.5 h. The C-terminal domain of nsp5 was shown to be required for the STAT3 degradation. Moreover, the STAT3 signaling in the cells transfected with nsp5 plasmid was significantly inhibited. These results indicate that PRRSV antagonizes the STAT3 signaling by accelerating STAT3 degradation via the ubiquitin-proteasomal pathway. This study provides insight into the PRRSV interference with the JAK/STAT3 signaling, leading to perturbation of the host innate and adaptive immune responses. The typical features of immune responses in PRRSV-infected pigs are delayed onset and low levels of virus neutralizing antibodies, as well as weak cell-mediated immunity. Lymphocyte development and differentiation rely on cytokines, many of which signal through the JAK/STAT signaling pathway to exert their biological effects. Here, we discovered that PRRSV antagonizes the

  4. 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 .

  5. 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)].

  6. 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.

  7. IL-23R–activated STAT3/STAT4 is essential for Th1/Th17-mediated CNS autoimmunity

    PubMed Central

    Lee, Priscilla W.; Smith, Alan J.; Yang, Yuhong; Selhorst, Amanda J.; Liu, Yue; Racke, Michael K.; Lovett-Racke, Amy E.

    2017-01-01

    The factors that promote the differentiation of pathogenic T cells in autoimmune diseases are poorly defined. Use of genetically modified mice has provided insight into molecules necessary for the development of autoimmunity, but the sum of the data has led to contradictory observations based on what is currently known about specific molecules in specific signaling pathways. To define the minimum signals required for development of encephalitogenic T cells that cause CNS autoimmunity, myelin-specific T cells were differentiated with various cytokine cocktails, and pathogenicity was determined by transfer into mice. IL-6+IL-23 or IL-12+IL-23 generated encephalitogenic T cells and recapitulated the essential cytokine signals provided by antigen-presenting cells, and both IL-6 and IL-12 induced IL-23 receptor expression on both mouse and human naive T cells. IL-23 signaled through both STAT3 and STAT4, and disruption in STAT4 signaling impaired CNS autoimmunity independent of IL-12. These data explain why IL-12–deficient mice develop CNS autoimmunity, while STAT4-deficient mice are resistant. CD4+ memory T cells from multiple sclerosis patients had significantly higher levels of p-STAT3/p-STAT4, and p-STAT3/p-STAT4 heterodimers were observed upon IL-23 signaling, suggesting that p-STAT3/p-STAT4 induced by IL-23 signaling orchestrate the generation of pathogenic T cells in CNS autoimmunity, regardless of Th1 or Th17 phenotype. PMID:28878115

  8. IL-23R-activated STAT3/STAT4 is essential for Th1/Th17-mediated CNS autoimmunity.

    PubMed

    Lee, Priscilla W; Smith, Alan J; Yang, Yuhong; Selhorst, Amanda J; Liu, Yue; Racke, Michael K; Lovett-Racke, Amy E

    2017-09-07

    The factors that promote the differentiation of pathogenic T cells in autoimmune diseases are poorly defined. Use of genetically modified mice has provided insight into molecules necessary for the development of autoimmunity, but the sum of the data has led to contradictory observations based on what is currently known about specific molecules in specific signaling pathways. To define the minimum signals required for development of encephalitogenic T cells that cause CNS autoimmunity, myelin-specific T cells were differentiated with various cytokine cocktails, and pathogenicity was determined by transfer into mice. IL-6+IL-23 or IL-12+IL-23 generated encephalitogenic T cells and recapitulated the essential cytokine signals provided by antigen-presenting cells, and both IL-6 and IL-12 induced IL-23 receptor expression on both mouse and human naive T cells. IL-23 signaled through both STAT3 and STAT4, and disruption in STAT4 signaling impaired CNS autoimmunity independent of IL-12. These data explain why IL-12-deficient mice develop CNS autoimmunity, while STAT4-deficient mice are resistant. CD4+ memory T cells from multiple sclerosis patients had significantly higher levels of p-STAT3/p-STAT4, and p-STAT3/p-STAT4 heterodimers were observed upon IL-23 signaling, suggesting that p-STAT3/p-STAT4 induced by IL-23 signaling orchestrate the generation of pathogenic T cells in CNS autoimmunity, regardless of Th1 or Th17 phenotype.

  9. Anopheles gambiae Ag-STAT, a new insect member of the STAT family, is activated in response to bacterial infection.

    PubMed Central

    Barillas-Mury, C; Han, Y S; Seeley, D; Kafatos, F C

    1999-01-01

    A new insect member of the STAT family of transcription factors (Ag-STAT) has been cloned from the human malaria vector Anopheles gambiae. The domain involved in DNA interaction and the SH2 domain are well conserved. Ag-STAT is most similar to Drosophila D-STAT and to vertebrate STATs 5 and 6, constituting a proposed ancient class A of the STAT family. The mRNA is expressed at all developmental stages, and the protein is present in hemocytes, pericardial cells, midgut, skeletal muscle and fat body cells. There is no evidence of transcriptional activation following bacterial challenge. However, bacterial challenge results in nuclear translocation of Ag-STAT protein in fat body cells and induction of DNA-binding activity that recognizes a STAT target site. In vitro treatment with pervanadate (vanadate and H2O2) translocates Ag-STAT to the nucleus in midgut epithelial cells. This is the first evidence of direct participation of the STAT pathway in immune responses in insects. PMID:10022838

  10. 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.

  11. 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

  12. A pilot assessment of alpha-stat vs pH-stat arterial blood gas analysis after cardiac arrest.

    PubMed

    Eastwood, Glenn M; Suzuki, Satoshi; Lluch, Cristina; Schneider, Antoine G; Bellomo, Rinaldo

    2015-02-01

    Resuscitated cardiac arrest (CA) patients typically receive therapeutic hypothermia, but arterial blood gases (ABGs) are often assessed after adjustment to 37°C (alpha-stat) instead of actual body temperature (pH-stat). We sought to compare alpha-stat and pH-stat assessment of PaO2 and PaCO2 in such patients. Using ABG data obtained during the first 24 hours of intensive care unit admission, we determined the impact of measured alpha vs calculated pH-stat on PaO2 and PaCO2 on patient classification and outcomes for CA patients. We assessed 1013 ABGs from 120 CA patients with a median age of patients 66 years (interquartile range, 50-76). Median alpha-stat PaO2 changed from 122 (95-156) to 107 (82-143) mm Hg with pH-stat and median PaCO2 from 39 (34-46) to 35 (30-41) mm Hg (both P < .001). Using the categories of hyperoxemia, normoxemia, and hypoxemia, pH-stat estimation of PaO2 reclassified approximately 20% of patients. Using the categories of hypercapnia, normocapnia, and hypocapnia, pH stat estimation of PaCO2 reclassified approximately 40% of patients. The mortality of patients in different PaO2 and PaCO2 categories was similar for pH-stat and alpha-stat. Using the pH-stat method, fewer resuscitated CA patients admitted to intensive care unit were classified as hyperoxemic or hypercapnic compared with alpha-stat. These findings suggest an impact of ABG assessment methodology on PaO2, PaCO2 , and patient classification but not on associated outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. 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

  14. JAK/STAT pathway dysregulation in tumors: A Drosophila perspective

    PubMed Central

    Amoyel, Marc; Anderson, Abigail M.; Bach, Erika A.

    2014-01-01

    Sustained activation of the JAK/STAT pathway is causal to human cancers. This pathway is less complex in Drosophila, and its dysregulation has been linked to several tumor models in this organism. Here, we discuss models of metastatic epithelial and hematopoietic tumors that are causally linked to dysregulation of JAK/STAT signaling in Drosophila. First, we focus on cancer models in imaginal discs where ectopic expression of the JAK/STAT pathway ligand Unpaired downstream of distinct tumor suppressors has emerged as an unexpected mediator of neoplastic transformation. We also discuss the collaboration between STAT and oncogenic Ras in epithelial transformation. Second, we examine hematopoietic tumors, where mutations that cause hyperactive JAK/STAT signaling are necessary and sufficient for “fly leukemia”. We highlight the important contributions that genetic screens in Drosophila have made to understanding the JAK/STAT pathway, its developmental roles, and how its function is co-opted during tumorigenesis. PMID:24685611

  15. 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.

  16. '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.'

  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. Spirit Slipping in Soft Ground, Sol 1889

    NASA Image and Video Library

    2009-05-01

    NASA's Mars Exploration Rover Spirit slipped in soft ground during short backward drives on the 1,886th and 1,889th Martian days, or sols, of the rover's mission on Mars (April 23 and 26, 2009). Spirit used its front hazard-avoidance camera after driving on Sol 1889 to get this wide-angle view, which shows the soil disturbed by the drives. Spirit drove 1.11 meters (3.6 feet) on Sol 1889 and 1.68 meters (5.5 feet) on Sol 1886. The rover drags its right front wheel, which no longer rotates. For scale, the distance between the wheel tracks is about 1 meter (40 inches). This view is looking northward, with Husband Hill on the horizon. http://photojournal.jpl.nasa.gov/catalog/PIA12002

  19. 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.

  20. 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.

  1. 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.

  2. Spirit Photographs Her Underbelly, SOL 1925

    NASA Image and Video Library

    2009-06-03

    This panorama of images from the Spirit rover, taken on Sol 1925 June 2, 2009, is helping engineers assess the rover current state and plan her extraction from the soft soil in the region now called Troy.

  3. 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

  4. 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

  5. Mechanisms of Unphosphorylated STAT3 Transcription Factor Binding to DNA*

    PubMed Central

    Timofeeva, Olga A.; Chasovskikh, Sergey; Lonskaya, Irina; Tarasova, Nadya I.; Khavrutskii, Lyuba; Tarasov, Sergey G.; Zhang, Xueping; Korostyshevskiy, Valeriy R.; Cheema, Amrita; Zhang, Lihua; Dakshanamurthy, Sivanesan; Brown, Milton L.; Dritschilo, Anatoly

    2012-01-01

    Phosphorylation of signal transducer and activator of transcription 3 (STAT3) on a single tyrosine residue in response to growth factors, cytokines, interferons, and oncogenes activates its dimerization, translocation to the nucleus, binding to the interferon γ (gamma)-activated sequence (GAS) DNA-binding site and activation of transcription of target genes. STAT3 is constitutively phosphorylated in various cancers and drives gene expression from GAS-containing promoters to promote tumorigenesis. Recently, roles for unphosphorylated STAT3 (U-STAT3) have been described in response to cytokine stimulation, in cancers, and in maintenance of heterochromatin stability. However, the mechanisms underlying U-STAT3 binding to DNA has not been fully investigated. Here, we explore STAT3-DNA interactions by atomic force microscopy (AFM) imaging. We observed that U-STAT3 molecules bind to the GAS DNA-binding site as dimers and monomers. In addition, we observed that U-STAT3 binds to AT-rich DNA sequence sites and recognizes specific DNA structures, such as 4-way junctions and DNA nodes, within negatively supercoiled plasmid DNA. These structures are important for chromatin organization and our data suggest a role for U-STAT3 as a chromatin/genome organizer. Unexpectedly, we found that a C-terminal truncated 67.5-kDa STAT3 isoform recognizes single-stranded spacers within cruciform structures that also have a role in chromatin organization and gene expression. This isoform appears to be abundant in the nuclei of cancer cells and, therefore, may have a role in regulation of gene expression. Taken together, our data highlight novel mechanisms by which U-STAT3 binds to DNA and supports U-STAT3 function as a transcriptional activator and a chromatin/genomic organizer. PMID:22378781

  6. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. 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.

  8. 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.

  9. 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…

  10. 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…

  11. 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.

  12. 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.

  13. 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.

  14. JAK-STAT in heterochromatin and genome stability.

    PubMed

    Silver-Morse, Louise; Li, Willis X

    2013-07-01

    The canonical JAK-STAT signaling pathway transmits signals from the cell membrane to the nucleus, to regulate transcription of particular genes involved in development and many other physiological processes. It has been shown in Drosophila that JAK and STAT also function in a non-canonical mode, to regulate heterochromatin. This review discusses the non-canonical functioning of JAK and STAT, and its effects on biological processes. Decreased levels of activated JAK and increased levels of unphosphorylated STAT generate higher levels of heterochromatin. These higher heterochromatin levels result in suppression of hematopoietic tumor-like masses, increased resistance to DNA damage, and longer lifespan.

  15. Hepatoprotective versus Oncogenic Functions of STAT3 in Liver Tumorigenesis

    PubMed Central

    Wang, Hua; Lafdil, Fouad; Wang, Lei; Park, Ogyi; Yin, Shi; Niu, Junyang; Miller, Andrew M.; Sun, Zhaoli; Gao, Bin

    2011-01-01

    Aberrantly hyperactivated STAT3 has been found in human liver cancers as an oncogene; however, STAT3 has also been shown to exert hepatoprotective effects during liver injury. The balancing act that STAT3 plays between hepatoprotection and liver tumorigenesis remains poorly defined. In this study, the diethylnitrosamine (DEN)-induced liver tumor model and the chronic carbon tetrachloride (CCl4)–induced liver fibrosis model were both used to investigate the role of STAT3 in liver tumorigenesis. Hepatocyte-specific STAT3 knockout mice were resistant to liver tumorigenesis induced by a single DEN injection, whose tumorigenesis was associated with minimal chronic liver inflammation, injury, and fibrosis. In contrast, long-term CCl4 treatment resulted in severe hepatic oxidative damage, inflammation, and fibrosis but rarely induced liver tumor formation in wild-type mice. Despite the oncogenic function of STAT3 in DEN-induced liver tumor, hepatocyte-specific STAT3 knockout mice were more susceptible to liver tumorigenesis after 16 weeks of CCl4 injection, which was associated with higher levels of liver injury, inflammation, fibrosis, and oxidative DNA damage compared with wild-type mice. These findings suggest that the hepatoprotective feature of STAT3 prevents hepatic damage and fibrosis under the condition of persistent inflammatory stress, consequently suppressing injury-driven liver tumor initiation. Once liver tumor cells have developed, STAT3 likely acts as an oncogenic factor to promote tumor growth. PMID:21684247

  16. 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

  17. 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.

  18. Reply to “Comment on ‘Piezonuclear decay of thorium’ [Phys. Lett. A 373 (2009) 1956]” [Phys. Lett. A 373 (2009) 3795

    NASA Astrophysics Data System (ADS)

    Cardone, Fabio; Mignani, Roberto; Petrucci, Andrea

    2009-10-01

    In a paper appearing in this issue of Physics Letters A, Ericsson et al. raise some critical comments on the experiment [F. Cardone, R. Mignani, A. Petrucci, Phys. Lett. A 373 (2009) 1956] we carried out by cavitating a solution of thorium-228, which evidenced its anomalous decay behaviour, thus confirming the results previously obtained by Urutskoev et al. by explosion of titanium foils in solutions. In this Letter, we reply to these comments. In our opinion, the main shortcomings of the criticism by the Swedish authors are due to their omitting of inserting our experiment in the wider research stream of piezonuclear reactions, and to the statistical analysis they used, which does not comply with the rules generally accepted for samples with small numbers. However, apart from any possible theoretical speculation, there is the basic fact that two different experiments (ours and that by Urutskoev et al.), carried out independently and by different means, highlight an analogous anomaly in the decay of thorium subjected to pressure waves. Such a convergence of results shows that it is worth to further carry on experimental investigations, in order to get either a confirmation or a disproof of the induced-pressure anomalous behaviour of radioactive nuclides even different from thorium.

  19. Salinomycin Abolished STAT3 and STAT1 Interactions and Reduced Telomerase Activity in Colorectal Cancer Cells.

    PubMed

    Chung, Seyung S; Adekoya, Debbie; Enenmoh, Ikechukwu; Clarke, Orette; Wang, Piwen; Sarkyssian, Marianna; Wu, Yong; Vadgama, Jaydutt V

    2017-02-01

    Colorectal cancer is the third leading cause of cancer-related mortality in most developed countries. This mortality is mainly due to the metastatic progression to the liver with frequent recurrence. Colorectal cancer remains a therapeutic challenge and this has intensified the search for new drug targets. In an effort to establish a novel targeted-therapy, we studied the molecular mechanisms of cancer stem cell inhibitor salinomycin. Co-immunoprecipitation was performed to examine STAT3-STAT1 protein interactions. Telomerase activity was measured by polymerase chain reaction (PCR) and ELISA assays. Apoptosis and cell stress arrays were analyzed to identify key proteins responding to salinomycin treatments. IL-6 and TNF-α induced STAT3 and STAT1 interactions, however the interactions were abolished by salinomycin challenge. Salinomycin reduced cancer stem cell phenotype and decreased telomerase activity of colorectal cancer cells. Our work uncovers a new mechanism through which salinomycin inhibits cancer stemness suggesting a novel targeted-therapy for metastatic colorectal cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  20. 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.

  1. 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

  2. Using the PhysX engine for physics-based virtual surgery with force feedback.

    PubMed

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

    2009-09-01

    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. 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. 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. 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 modelling strategies for behaviour, collision and

  3. 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

  4. Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population: a case-control association study of the STAT1-STAT4 region.

    PubMed

    Kawasaki, Aya; Ito, Ikue; Hikami, Koki; Ohashi, Jun; Hayashi, Taichi; Goto, Daisuke; Matsumoto, Isao; Ito, Satoshi; Tsutsumi, Akito; Koga, Minori; Arinami, Tadao; Graham, Robert R; Hom, Geoffrey; Takasaki, Yoshinari; Hashimoto, Hiroshi; Behrens, Timothy W; Sumida, Takayuki; Tsuchiya, Naoyuki

    2008-01-01

    Recent studies identified STAT4 (signal transducers and activators of transcription-4) as a susceptibility gene for systemic lupus erythematosus (SLE). STAT1 is encoded adjacently to STAT4 on 2q32.2-q32.3, upregulated in peripheral blood mononuclear cells from SLE patients, and functionally relevant to SLE. This study was conducted to test whether STAT4 is associated with SLE in a Japanese population also, to identify the risk haplotype, and to examine the potential genetic contribution of STAT1. To accomplish these aims, we carried out a comprehensive association analysis of 52 tag single nucleotide polymorphisms (SNPs) encompassing the STAT1-STAT4 region. In the first screening, 52 tag SNPs were selected based on HapMap Phase II JPT (Japanese in Tokyo, Japan) data, and case-control association analysis was carried out on 105 Japanese female patients with SLE and 102 female controls. For associated SNPs, additional cases and controls were genotyped and association was analyzed using 308 SLE patients and 306 controls. Estimation of haplotype frequencies and an association study using the permutation test were performed with Haploview version 4.0 software. Population attributable risk percentage was estimated to compare the epidemiological significance of the risk genotype among populations. In the first screening, rs7574865, rs11889341, and rs10168266 in STAT4 were most significantly associated (P < 0.01). Significant association was not observed for STAT1. Subsequent association studies of the three SNPs using 308 SLE patients and 306 controls confirmed a strong association of the rs7574865T allele (SLE patients: 46.3%, controls: 33.5%, P = 4.9 x 10(-6), odds ratio 1.71) as well as TTT haplotype (rs10168266/rs11889341/rs7574865) (P = 1.5 x 10(-6)). The association was stronger in subgroups of SLE with nephritis and anti-double-stranded DNA antibodies. Population attributable risk percentage was estimated to be higher in the Japanese population (40.2%) than in

  5. 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.

  6. 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.

  7. 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.

  8. Growth hormone activation of Stat 1, Stat 3, and Stat 5 in rat liver. Differential kinetics of hormone desensitization and growth hormone stimulation of both tyrosine phosphorylation and serine/threonine phosphorylation.

    PubMed

    Ram, P A; Park, S H; Choi, H K; Waxman, D J

    1996-03-08

    Intermittent plasma growth hormone (GH) pulses, which occur in male but not female rats, activate liver Stat 5 by a mechanism that involves tyrosine phosphorylation and nuclear translocation of this latent cytoplasmic transcription factor (Waxman, D. J., Ram, P. A., Park, S. H., and Choi, H. K. (1995) J. Biol. Chem. 270, 13262-13270). We demonstrate that physiological levels of GH can also activate Stat 1 and Stat 3 in liver tissue, but with a dependence on the dose of GH and its temporal plasma profile that is distinct from Stat 5 and with a striking desensitization following a single hormone pulse that is not observed with liver Stat 5. GH activation of the two groups of Stats leads to their selective binding to DNA response elements upstream of the c-fos gene (c-sis-inducible enhancer element; Stat 1 and Stat 3 binding) and the beta-casein gene (mammary gland factor element; liver Stat 5 binding). In addition to tyrosine phosphorylation, GH is shown to stimulate phosphorylation of these Stats on serine or threonine in a manner that either enhances (Stat 1 and Stat 3) or substantially alters (liver Stat 5) the binding of each Stat to its cognate DNA response element. These findings establish the occurrence of multiple, Stat-dependent GH signaling pathways in liver cells that can target distinct genes and thereby contribute to the diverse effects that GH and its sexually dimorphic plasma profile have on liver gene expression.

  9. 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

  10. Non-genomic STAT5-dependent effects at the endoplasmic reticulum and Golgi apparatus and STAT6-GFP in mitochondria

    PubMed Central

    Sehgal, Pravin B

    2013-01-01

    STAT protein species are well-known as transcription factors that regulate nuclear gene expression. Recent novel lines of research suggest new non-genomic functions of STAT5A/B and STAT6. It was discovered in human pulmonary arterial endothelial cells that STAT5A, including STAT5A-GFP, constitutively associated with the Golgi apparatus, and both STAT5A and B with the endoplasmic reticulum. Acute siRNA-mediated knockdown of STAT5A/B led to the rapid development of a dramatic cystic change in the endoplasmic reticulum (ER) characterized by deposition of the ER structural protein reticulon-4 (RTN4; also called Nogo-B) and the ER-resident GTPase atlastin-3 (ATL3) along cyst membranes and cyst-zone boundaries, accompanied by Golgi fragmentation. Functional consequences included reduced anterograde trafficking, an ER stress response (increased GRP78/BiP) and eventual mitochondrial fragmentation. This phenotype was “non-genomic” in that it was elicited in enucleated cytoplasts. In cross-immunopanning assays STAT5A and B species associated with ATL3, and the ER-lumen spacer CLIMP63 (also called cytoskeleton-associated protein 4, CKAP4) but not RTN4. From a disease significance perspective we posit that STAT5, which is known to be affected by estradiol-17β and prolactin, represents the gender-sensitive determinant in the pathogenesis of idiopathic pulmonary hypertension (IPAH), a disease which includes ER/Golgi dysfunctions but with a 2- to 4-fold higher prevalence in postpubertal women. A separate line of recent research produced evidence for the association of STAT6-GFP, but not STAT3-GFP, STAT3-DsRed, or STAT3-Flag, with mitochondria in live-cell, immunofluorescence, and immunoelectron microscopy. An N-terminal truncation of STAT6-GFP (1–459), which lacked the SH2 domain and Tyr-phosphorylation site, constitutively associated with mitochondria. Thus, the emergent new of biology STAT proteins includes non-genomic roles—structurally and functionally—in the three

  11. Genetic Interactions of STAT3 and Anticancer Drug Development

    PubMed Central

    Fang, Bingliang

    2014-01-01

    Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors. PMID:24662938

  12. 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.

  13. JAK-STAT in lipid metabolism of adipocytes.

    PubMed

    Xu, Dong; Yin, Chunyan; Wang, Sisi; Xiao, Yanfeng

    2013-10-01

    JAK-STAT signaling pathway plays an important role in the cells' development and homeostasis. Over the past decades, the studies have identified the role of the JAK-STAT pathway in cell proliferation and apoptosis. Here, we want to discuss that whether and how the JAK-STAT pathway affects the lipid metabolism of adipose tissue. A host of cytokines and hormones can regulate lipid metabolism through activating the JAK-STAT signaling pathway. Activated STATs can regulate lipid metabolism directly by influencing the expression of enzymes. We have summarized the relevant research and articles of JAK-STAT during the recent years. Within this review, we will introduce you the recent research and highlight the unresolved problems in understanding how JAK-STAT signaling pathway contribute to the lipid metabolism in mature adipocytes and preadipocytes. Dysregulation of the JAK-STAT pathway would lead to a multiple metabolism disorders and medicines for this signaling pathway maybe become a new idea for diseases such as metabolic syndrome, especially in children.

  14. The spectrum of STAT functions in mammary gland development

    PubMed Central

    Hughes, Katherine; Watson, Christine J.

    2012-01-01

    The signal transducer and activator of transcription (STAT) family of transcription factors have a spectrum of functions in mammary gland development. In some cases these roles parallel those of STATs in other organ systems, while in other instances the function of individual STATs in the mammary gland is specific to this tissue. In the immune system, STAT6 is associated with differentiation of T helper cells, while in the mammary gland, it has a fundamental role in the commitment of luminal epithelial cells to the alveolar lineage. STAT5A is required for the production of luminal progenitor cells from mammary stem cells and is essential for the differentiation of milk producing alveolar cells during pregnancy. By contrast, the initiation of regression following weaning heralds a dramatic and specific activation of STAT3, reflecting its pivotal role in the regulation of cell death and tissue remodeling during mammary involution. Although it has been demonstrated that STAT1 is regulated during a mammary developmental cycle, it is not yet determined whether it has a specific, non-redundant function. Thus, the mammary gland constitutes an unusual example of an adult organ in which different STATs are sequentially activated to orchestrate the processes of functional differentiation, cell death and tissue remodeling. PMID:24058764

  15. Acetylation of Stat1 modulates NF-κB activity

    PubMed Central

    Krämer, Oliver H.; Baus, Daniela; Knauer, Shirley K.; Stein, Stefan; Jäger, Elke; Stauber, Roland H.; Grez, Manuel; Pfitzner, Edith; Heinzel, Thorsten

    2006-01-01

    Acetylation of signaling molecules can lead to apoptosis or differentiation of carcinoma cells. The molecular mechanisms underlying these processes and the biological role of enzymes mediating the transfer or removal of an acetyl-group are currently under intense investigation. Our study shows that Stat1 is an acetylated protein. Stat1 acetylation depends on the balance between Stat1-associated histone deacetylases (HDACs) and histone acetyltransferases (HATs) such as CBP. Remarkably both inhibitors of HDACs and the cytokine interferon α alter this equilibrium and induce Stat1 acetylation. The analysis of Stat1 mutants reveals Lys 410 and Lys 413 as acetylation sites. Experiments with Stat1 mutants mimicking either constitutively acetylated or nonacetylated states show that only acetylated Stat1 is able to interact with NF-κB p65. As a consequence, p65 DNA binding, nuclear localization, and expression of anti-apoptotic NF-κB target genes decrease. These findings show how the acetylation of Stat1 regulates NF-κB activity and thus ultimately apoptosis. PMID:16481475

  16. Psychometric Properties of the STAT for Early Autism Screening

    ERIC Educational Resources Information Center

    Stone, Wendy L.; Coonrod, Elaine E.; Turner, Lauren M.; Pozdol, Stacie L.

    2004-01-01

    The STAT is an interactive screening measure for autism that assesses behaviors in the areas of play, communication, and imitation skills. In Study 1, signal detection procedures were employed to identify a cutoff score for the STAT using developmentally matched groups of 2-year-old children with autism and with nonspectrum disorders. The…

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. Cloning of a new type II cytokine receptor activating signal transducer and activator of transcription (STAT)1, STAT2 and STAT3.

    PubMed Central

    Dumoutier, Laure; Lejeune, Diane; Hor, Simon; Fickenscher, Helmut; Renauld, Jean-Christophe

    2003-01-01

    In the present paper, we report the identification of a new gene encoding a transmembrane protein of 520 amino acids, showing 22% amino acid identity with the extracellular domain of the interleukin (IL)-20 receptor. This gene, termed likely interleukin or cytokine receptor-2 ( LICR2 ), is located on chromosome 1, at 25 kb from the IL22R (IL-22 receptor) gene, and is constitutively expressed in most tissues. A chimaeric receptor, consisting of the extracellular domain of the IL-10 receptor alpha chain and the intracellular domain of LICR2, activated signal transducer and activator of transcription (STAT)1, STAT2, STAT3 and STAT5 upon IL-10 stimulation, in a Janus kinase 1-dependent manner. In contrast, none of the IL-10-related cytokines described so far could activate LICR2-transfected cells, suggesting that LICR2 is a signalling receptor for a new cytokine of the IL-10 family. PMID:12521379

  3. 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.

  4. 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.

  5. 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

  6. STAT3 Regulation of Glioblastoma Pathogenesis

    PubMed Central

    de la Iglesia, Núria; Puram, Sidharth V.; Bonni, Azad

    2009-01-01

    Malignant gliomas are the most common primary brain tumors. Despite efforts to find effective treatments, these tumors remain incurable. The failure of malignant gliomas to respond to conventional cancer therapies may reflect the unique biology of these tumors, underscoring the need for new approaches in their investigation. Recently, progress has been made in characterization of the molecular pathogenesis of glioblastoma using a developmental neurobiological perspective, by exploring the role of signaling pathways that control the differentiation of neural stem cells along the glial lineage. The transcription factor STAT3, which has an established function in neural stem cell and astrocyte development, has been found to play dual tumor suppressive and oncogenic roles in glial malignancy depending on the mutational profile of the tumor. These findings establish a novel developmental paradigm in the study of glioblastoma pathogenesis and provide the rationale for patient-tailored therapy in the treatment of this devastating disease. PMID:19601808

  7. Curiosity Arm Holding Steady, Sol 915

    NASA Image and Video Library

    2015-03-06

    This image from the Navigation Camera (Navcam) on NASA's Curiosity Mars rover shows the position in which the rover held its arm for several days after a transient short circuit triggered onboard fault-protection programming to halt arm activities on Feb. 27, 2015, the 911th Martian day, or sol, of the rover's work on Mars. The rover team chose to hold the arm in the same position for several days of tests to diagnose the underlying cause of the Sol 911 event. Observations with instruments on the rover's mast continued during this period. The Navcam took this image on March 4, 2015, during Sol 915. http://photojournal.jpl.nasa.gov/catalog/PIA19147

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Comment on “Piezonuclear decay of thorium” [Phys. Lett. A 373 (2009) 1956

    NASA Astrophysics Data System (ADS)

    Ericsson, G.; Pomp, S.; Sjöstrand, H.; Traneus, E.

    2009-10-01

    Subjecting a solution of 228Th to ultrasound (20 kHz, 100 W), Cardone et al. [F. Cardone, R. Mignani, A. Petrucci, Phys. Lett. A 373 (2009) 1956] claim to observe an increase in the transformation or decay rate of 228Th by a factor of 10 4. The evidence provided seems however far from conclusive and in part contradictory to the claims made. In fact, looking at the presented data we find it cannot be taken as justification to discard the null hypothesis, namely, that the data from exposed and non-exposed samples are drawn from the same distribution. We suggest a number of additional tests that should be made in order to improve the quality of the study and test the hypothesis of so-called piezonuclear reactions.

  2. Comment on ``Minimum free-energy pathway of nucleation'' [J. Chem. Phys. 135, 134508 (2011)

    NASA Astrophysics Data System (ADS)

    Schmelzer, Jürn W. P.; Abyzov, Alexander S.

    2012-03-01

    In their recent paper [J. Chem. Phys. 135, 134508 (2011)], Philippe and Blavette, 10.1063/1.3644935 claimed to have found for the first time—based on minimum free energy considerations—that the nucleation pathway in solid solutions involves a universal two-step behavior: nuclei sharply enrich up to near equilibrium values of the concentration and then grow. This claim of priority is not correct. The same scenario was proposed by us long ago [J. W. P. Schmelzer, A. R. Gokhman, and V. M. Fokin, J. Colloid Interface Sci. 272, 109 (2004)], 10.1016/j.jcis.2003.08.038 and then applied and further developed. In particular, it was shown by us that only the account of both thermodynamic and kinetic factors allows one to determine correctly the most probable path of evolution in nucleation-growth processes. The two-step scenario is retained, however, also in these generalizations of our original approach.

  3. 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.

  4. 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

  5. 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

  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. 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

  8. 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.

  9. A partial form of recessive STAT1 deficiency in humans.

    PubMed

    Chapgier, Ariane; Kong, Xiao-Fei; Boisson-Dupuis, Stéphanie; Jouanguy, Emmanuelle; Averbuch, Diana; Feinberg, Jacqueline; Zhang, Shen-Ying; Bustamante, Jacinta; Vogt, Guillaume; Lejeune, Julien; Mayola, Eleonore; de Beaucoudrey, Ludovic; Abel, Laurent; Engelhard, Dan; Casanova, Jean-Laurent

    2009-06-01

    Complete STAT1 deficiency is an autosomal recessive primary immunodeficiency caused by null mutations that abolish STAT1-dependent cellular responses to both IFN-alpha/beta and IFN-gamma. Affected children suffer from lethal intracellular bacterial and viral diseases. Here we report a recessive form of partial STAT1 deficiency, characterized by impaired but not abolished IFN-alpha/beta and IFN-gamma signaling. Two affected siblings suffered from severe but curable intracellular bacterial and viral diseases. Both were homozygous for a missense STAT1 mutation: g.C2086T (P696S). This STAT1 allele impaired the splicing of STAT1 mRNA, probably by disrupting an exonic splice enhancer. The misspliced forms were not translated into a mature protein. The allele was hypofunctional, because residual full-length mRNA production resulted in low but detectable levels of normally functional STAT1 proteins. The P696S amino acid substitution was not detrimental. The patients' cells, therefore, displayed impaired but not abolished responses to both IFN-alpha and IFN-gamma. We also show that recessive STAT1 deficiencies impaired the IL-27 and IFN-lambda1 signaling pathways, possibly contributing to the predisposition to bacterial and viral infections, respectively. Partial recessive STAT1 deficiency is what we believe to be a novel primary immunodeficiency, resulting in impairment of the response to at least 4 cytokines (IFN-alpha/beta, IFN-gamma, IFN-lambda1, and IL-27). It should be considered in patients with unexplained, severe, but curable intracellular bacterial and viral infections.

  10. 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

  11. A partial form of recessive STAT1 deficiency in humans

    PubMed Central

    Chapgier, Ariane; Kong, Xiao-Fei; Boisson-Dupuis, Stéphanie; Jouanguy, Emmanuelle; Averbuch, Diana; Feinberg, Jacqueline; Zhang, Shen-Ying; Bustamante, Jacinta; Vogt, Guillaume; Lejeune, Julien; Mayola, Eleonore; de Beaucoudrey, Ludovic; Abel, Laurent; Engelhard, Dan; Casanova, Jean-Laurent

    2009-01-01

    Complete STAT1 deficiency is an autosomal recessive primary immunodeficiency caused by null mutations that abolish STAT1-dependent cellular responses to both IFN-α/β and IFN-γ. Affected children suffer from lethal intracellular bacterial and viral diseases. Here we report a recessive form of partial STAT1 deficiency, characterized by impaired but not abolished IFN-α/β and IFN-γ signaling. Two affected siblings suffered from severe but curable intracellular bacterial and viral diseases. Both were homozygous for a missense STAT1 mutation: g.C2086T (P696S). This STAT1 allele impaired the splicing of STAT1 mRNA, probably by disrupting an exonic splice enhancer. The misspliced forms were not translated into a mature protein. The allele was hypofunctional, because residual full-length mRNA production resulted in low but detectable levels of normally functional STAT1 proteins. The P696S amino acid substitution was not detrimental. The patients’ cells, therefore, displayed impaired but not abolished responses to both IFN-α and IFN-γ. We also show that recessive STAT1 deficiencies impaired the IL-27 and IFN-λ1 signaling pathways, possibly contributing to the predisposition to bacterial and viral infections, respectively. Partial recessive STAT1 deficiency is what we believe to be a novel primary immunodeficiency, resulting in impairment of the response to at least 4 cytokines (IFN-α/β, IFN-γ, IFN-λ1, and IL-27). It should be considered in patients with unexplained, severe, but curable intracellular bacterial and viral infections. PMID:19436109

  12. 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)].

  13. Sol-gel modification of wood substrates to retard weathering

    Treesearch

    Mandla A Tshabalala; Sam Williams

    2008-01-01

    Wood specimens were treated with sol-gel systems based on metalorganic precursors of silicon (Si), iron (Fe), zirconium (Zr), and titanium (Ti). The effect of these sol-gel systems on weathering properties of wood was investigated. These sol-gel systems were found to have a positive effect on surface color stability and water vapor resistance of the specimens. Under...

  14. Outdoor weathering of sol-gel-treated wood

    Treesearch

    Mandla A Tshabalala; Ryan Libert; Nancy Ross Sutherland

    2009-01-01

    Outdoor weathering of wood specimens treated with sol-gel formulations based on methyltrimethoxysilane (MTMOS), hexadecyltrimethoxysilane (HDTMOS), and ferric-zirconia-titania (Fe-Zr-Ti) sol was evaluated. The sol-gel process allowed deposition of a thin film of hybrid inorganic-organic networks (gel) in the wood cell wall that resulted in improved outdoor weathering...

  15. At Edge of Yellowknife Bay, Sol 130

    NASA Image and Video Library

    2012-12-21

    In a shallow depression called Yellowknife Bay, the NASA Mars rover Curiosity drove to an edge of the feature to record this view of the ledge at the margin and a view across the bay during the 130th Martian day, or sol, Dec. 17, 2012.

  16. Approaching Endeavour Crater, Sol 2,680

    NASA Image and Video Library

    2011-10-10

    This image from the navigation camera on NASA Mars Exploration Rover Opportunity shows the view ahead on the day before the rover reached the rim of Endeavour crater. It was taken during the 2,680th Martian day, or sol, of the rover work on Mars.

  17. 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.

  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 Martian Traverse Through Sol 2442

    NASA Image and Video Library

    2010-12-10

    The white line on this map shows where NASA Mars Rover Opportunity has driven from the place where it landed in January 2004 -- inside Eagle Crater, at the upper left end of the track -- to where it reached on the 2,442nd Martian day, or sol.

  20. Heading for Mount Sharp, Sol 329

    NASA Image and Video Library

    2013-07-11

    Lower slopes of Mount Sharp appear at the top of this image taken by the right Navigation Camera Navcam of NASA Mars rover Curiosity at the end of a drive of about 135 feet during the 329th Martian day, or sol, of the rover work on Mars.

  1. Response to interferons and antibacterial innate immunity in the absence of tyrosine-phosphorylated STAT1.

    PubMed

    Majoros, Andrea; Platanitis, Ekaterini; Szappanos, Daniel; Cheon, HyeonJoo; Vogl, Claus; Shukla, Priyank; Stark, George R; Sexl, Veronika; Schreiber, Robert; Schindler, Christian; Müller, Mathias; Decker, Thomas

    2016-03-01

    Signal transducer and activator of transcription 1 (STAT1) plays a pivotal role in the innate immune system by directing the transcriptional response to interferons (IFNs). STAT1 is activated by Janus kinase (JAK)-mediated phosphorylation of Y701. To determine whether STAT1 contributes to cellular responses without this phosphorylation event, we generated mice with Y701 mutated to a phenylalanine (Stat1(Y701F)). We show that heterozygous mice do not exhibit a dominant-negative phenotype. Homozygous Stat1(Y701F) mice show a profound reduction in Stat1 expression, highlighting an important role for basal IFN-dependent signaling. The rapid transcriptional response to type I IFN (IFN-I) and type II IFN (IFNγ) was absent in Stat1(Y701F) cells. Intriguingly, STAT1Y701F suppresses the delayed expression of IFN-I-stimulated genes (ISG) observed in Stat1(-/-) cells, mediated by the STAT2/IRF9 complex. Thus, Stat1(Y701F) macrophages are more susceptible to Legionella pneumophila infection than Stat1(-/-) macrophages. Listeria monocytogenes grew less robustly in Stat1(Y701F) macrophages and mice compared to Stat1(-/-) counterparts, but STAT1Y701F is not sufficient to rescue the animals. Our studies are consistent with a potential contribution of Y701-unphosphorylated STAT1 to innate antibacterial immunity. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  2. Differential activation of acute phase response factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130. I. Definition of a novel phosphotyrosine motif mediating STAT1 activation.

    PubMed

    Gerhartz, C; Heesel, B; Sasse, J; Hemmann, U; Landgraf, C; Schneider-Mergener, J; Horn, F; Heinrich, P C; Graeve, L

    1996-05-31

    Interleukin-6 (IL-6) and gamma-interferon (IFNgamma) activate an overlapping set of genes via the Jak/STAT pathway. However, at least in human cells, a differential activation of STAT transcription factors was observed: IL-6 activates both acute phase response factor (APRF)/STAT3 and STAT1, whereas IFNgamma leads only to STAT1 activation. All STATs cloned so far contain SH2 domains. Since all cytokine receptors using the Jak/STAT pathway were found to be tyrosine-phosphorylated after ligand binding, it has been proposed that specific phosphotyrosine modules within the cytoplasmic domain of the receptor chains recruit different STAT factors. We have analyzed by mutational studies and by phosphopeptide competition assays which of the tyrosine modules of the IL-6 signal transducer gp130 are capable of recruiting either APRF or STAT1. We found that two of the four tyrosine modules that are important for APRF activation also activate STAT1. For these modules, we propose the new consensus sequence YXPQ. We further present evidence that STAT1 is activated independently from APRF suggesting that gp130 contains multiple independent STAT binding sites. We compare the APRF and STAT1 activation motifs of gp130 with the STAT1 activation motif of the IFNgamma receptor and demonstrate that the specificity of activation can be changed from APRF to STAT1 and vice versa by only two point mutations within a tyrosine module. These data strongly support the concept that the activation of a specific STAT is determined mainly by the phosphotyrosine module. The significance of these findings for other receptor systems is discussed.

  3. 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).

  4. JAK-STAT and the renin-angiotensin system

    PubMed Central

    Satou, Ryousuke; Gonzalez-Villalobos, Romer A.

    2012-01-01

    The renin-angiotensin system (RAS) plays important roles in blood pressure control and tissue disease. An inappropriate local angiotensin II elevation in the kidneys leads to the development of hypertension, tissue damage and chronic injury. Studies have demonstrated that the JAK-STAT pathway mediates angiotensin II-triggered gene transcription. The JAK-STAT pathway in turn, acting as an amplifying system, contributes to further intrarenal RAS activation. These observations prompt the suggestion that the JAK-STAT pathway may be of importance in elucidating the mechanisms RAS-associated tissue injury. Accordingly, this review provides a brief overview of the interactions between the JAK-STAT pathway and the RAS, specifically the RAS expressed in the kidneys. PMID:24058780

  5. PREFACE: International Symposium "Nanoscience and Quantum Physics 2011" (nanoPHYS'11)

    NASA Astrophysics Data System (ADS)

    Saito, Susumu; Tanaka, Hidekazu; Nakamura, Takashi; Nakamura, Masaaki

    2011-07-01

    Quantum physics has developed modern views of nature for more than a century. In addition to this traditional role, quantum physics has acquired new significance in the 21st century as the field responsible for driving and supporting nanoscience research, which will have even greater importance in the future because nanoscience will be the academic foundation for new technologies. The Department of Physics, Tokyo Institute of Technology, are now conducting a "Nanoscience and Quantum Physics" project (Physics G-COE project) supported by the Global Center of Excellence Program of the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) in order to promote research and education in these important academic fields. The International Symposium on Nanoscience and Quantum Physics, held in Tokyo, Japan, 26-28 January 2011 (nanoPHYS'11) was organized by the Physics G-COE project of the Tokyo Institute of Technology to provide an international forum for the open exchange of topical information and for stimulating discussion on novel concepts and future prospects of nanoscience and quantum physics. There were a total of 118 papers including 34 invited papers. This nanoPHYS'11 is the fourth symposium of this kind organized by the Tokyo Institute of Technology. Topics focused on in the symposium included: Category 1: Novel nanostructure (Nanowires, Nanotubes, Spin-related structure, etc) Category 2: Novel transport and electronic properties (Graphene, Topological insulators, Coherent control, etc) Category 3: Electronic and optical properties of nanostructure Category 4: Fundamental physics and new concept in quantum physics Category 5: Quantum Physics - Quantum information Category 6: Quantum Physics - Nuclear and Hadron Physics Category 7: Quantum Physics - Astrophysics, etc All the papers submitted to this issue have been reviewed under a stringent refereeing process, according to the normal rules of this Journal. The editors are grateful to all the

  6. Cooperative DNA Binding and Sequence-Selective Recognition Conferred by the STAT Amino-Terminal Domain

    NASA Astrophysics Data System (ADS)

    Xu, Xiang; Sun, Ya-Lin; Hoey, Timothy

    1996-08-01

    STAT proteins (signal transducers and activators of transcription) activate distinct target genes despite having similar DNA binding preferences. The transcriptional specificity of STAT proteins was investigated on natural STAT binding sites near the interferon-gamma gene. These sites are arranged in multiple copies and required cooperative interactions for STAT binding. The conserved amino-terminal domain of STAT proteins was required for cooperative DNA binding, although this domain was not essential for dimerization or binding to a single site. Cooperative binding interactions enabled the STAT proteins to recognize variations of the consensus site. These sites can be specific for the different STAT proteins and may function to direct selective transcriptional activation.

  7. 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

  8. Using A3 thinking to improve the STAT medication process.

    PubMed

    Manojlovich, Milisa; Chase, Valerie J; Mack, Megan; Conroy, Meghan K; Belanger, Karen; Zawol, Debbie; Corr, Karen M; Fowler, Karen E; Viglianti, Elizabeth

    2014-08-01

    Although the term STAT conveys a sense of urgency, it is sometimes used to circumvent a system that may be too slow to accomplish tasks in a timely manner. We describe a quality-improvement project undertaken by a US Department of Veterans Affairs (VA) hospital to improve the STAT medication process. We adapted A3 Thinking, a problem-solving process common in Lean organizations, to our problem. In the discovery phase, a color-coded flow map of the existing process was constructed, and a real-time STAT order was followed in a modified "Go to the Gemba" exercise. In the envisioning phase, the team brainstormed to come up with as many improvement ideas as possible, which were then prioritized based on the anticipated effort and impact. The team then identified initial experiments to be carried out in the experimentation phase; each experiment followed a standard Plan-Do-Study-Act cycle. On average, the number of STAT medications ordered per month decreased by 9.5%. The average time from STAT order entry to administration decreased by 21%, and time from medication delivery to administration decreased by 26%. Improvements were also made in technician awareness of STAT medications and nurse notification of STAT medication delivery. Adapting A3 Thinking for process improvement was a low-cost/low-tech option for a VA facility. The A3 Thinking process led to a better understanding of the meaning of STAT across disciplines, and promoted a collaborative culture in which other hospital-wide problems may be addressed in the future. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  9. Urokinase induces activation of STAT3 in lung epithelial cells.

    PubMed

    Shetty, Sreerama; Rao, Gadiparthi N; Cines, Douglas B; Bdeir, Khalil

    2006-10-01

    Urokinase-type plasminogen activator (uPA) is a serine protease that plays a major role in diverse physiological and pathological processes. Studies from our laboratory have shown that exposure of human lung epithelial cells to uPA induces proliferation. To understand uPA mitogenic signaling events, we sought to elucidate its effects on tyrosine phosphorylation in a human bronchial epithelial cell line (Beas2B). uPA induced tyrosine phosphorylation of several proteins in a time-dependent manner. One of these proteins was identified as the 91-kDa signal transduction activator transcription (Stat)3 moiety. Tyrosine phosphorylation of Stat3 by uPA was time dependent. uPA induced Stat3-DNA binding activity in a time-dependent manner. uPA-induced Stat3 activation does not require uPA catalytic activity, as the uPA amino-terminal fragment alone was as potent as active two-chain uPA (tcuPA) in causing this effect. Single-chain uPA likewise induced tyrosine phosphorylation of Stat3 to a similar extent as intact tcuPA. Plasmin did not alter uPA-induced Stat3 activation. Furthermore, transfection of Beas2B cells with dominant-negative Stat3 blocked uPA-induced DNA synthesis. These results reveal for the first time that the uPA-uPAR interaction leads to activation of Stat3, independent of its catalytic activity but dependent on its interaction with its receptor, uPAR, leading to DNA synthesis in lung epithelial cells.

  10. 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…

  11. 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…

  12. 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.

  13. STAT signaling in different breast cancer sub-types.

    PubMed

    Furth, Priscilla A

    2014-01-25

    This review summarizes information on expression of Signal Transducer and Activator of Transcription (STAT)s 1, 2, 3, 4, 5a/b and 6 in cancer cells from different human breast cancer sub-types. STAT proteins, especially STATs 1, 3 and 5a/b are expressed in some but not all cancers from all of the different major breast cancer sub-types. However, well-designed studies comparing expression patterns at the protein level in cancer and surrounding stromal cells are still needed to fully examine links with prognosis and therapeutic response. Moreover, it is not yet known if distinct expression patterns of STAT proteins could have dissimilar impacts in different sub-types, especially between the luminal A and B ER+ sub-types and the different TNBC sub-types. Recent data indicating that STAT 5 can be activated secondary to a therapeutic intervention and mediate resistance suggests that expression patterns should not only be examined in pre-treatment but also post-treatment samples from different sub-types. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed Central

    Haricharan, S; Li, Y

    2013-01-01

    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, programed 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. PMID:23541951

  15. 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.

  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. Application of genomic DNA affinity chromatography identifies multiple interferon-alpha-regulated Stat2 complexes.

    PubMed

    Ghislain, J J; Fish, E N

    1996-05-24

    Interferon-alpha (IFN-alpha)-induced signal transduction is mediated by the phosphorylation-activation of the signal transducer and activator of transcription (STAT) proteins Stat1, Stat2, and Stat3. Previous studies have shown that these activated STATs dimerize to form four distinct STAT complexes which translocate to the nucleus and activates transcription by binding to specific promoter elements. The interferon-stimulated gene factor-3 (ISGF3) consists of Stat2 and Stat1 heterodimers in association with a DNA-binding protein, p48, that binds to the interferon stimulated response element. Homo-and heterodimers of Stat1 and Stat3 bind to the palindromic interferon response element (pIRE). In this report we demonstrate the utility of a biochemical procedure that we have developed, based on genomic DNA affinity chromatography, for the identification of IFN-alpha-induced STAT complexes. Using this approach, we identified ISGF3-independent Stat2-containing STAT complexes. Results from the analysis of Stat2 complexes in the electrophoretic mobility shift assay were consistent with genomic DNA affinity chromatography results and identified a Stat2:1 complex that binds with low affinity to the pIRE of the interferon regulatory factor-1 gene. Immunoprecipitation studies of Stat2 revealed an IFN-alpha dependent co-precipitation of both Stat1 and Stat3. Taken together, our results suggest that IFN-alpha activates, in addition to ISGF3, other Stat2-containing STAT complexes, one of which binds to an element related to the interferon regulatory factor-1 pIRE.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. Reply to “Comment on ‘Gauge invariance and k-factorization of exclusive processes’ [Phys. Lett. B 674 (2009) 176]” [Phys. Lett. B 674 (2009) 182

    NASA Astrophysics Data System (ADS)

    Feng, F.; Ma, J. P.; Wang, Q.

    2009-06-01

    A new method is proposed to calculate wave functions in kT-factorization in [H.-n. Li, S. Mishima, Phys. Lett. B 674 (2009) 182, arXiv:0808.1526] as a comment about our paper [F. Feng, J.P. Ma, Q. Wang, Phys. Lett. B 674 (2009) 176, arXiv:0807.0296]. We point out that the results obtained with the method are in conflict with the translation invariance and depend on the chosen contours for loop-integrals. Therefore, the method is in principle unacceptable and the results with the method cannot be correct.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Amorphous sol-gel insulating films

    SciTech Connect

    Brinker, C.J. |; Warren, W.L.; Logan, M.N.; Ashley, C.S.

    1993-05-01

    The porosity of sol-gel thin films may be tailored for specific applications through control of the size and structure of inorganic polymers within the coating sol, the extent of polymer reaction and interpenetration during film formation, and the magnitude of the capillary pressure exerted during the final stage of drying. By maximizing the capillary pressure and avoiding excessive condensation, dense insulating films may be prepared as passivation layers on silicon substrates. Such films can exhibit excellent dielectric integrity, viz., low interface trap densities and insulating properties approaching those of thermally grown SiO{sub 2}. Alternatively, through exploitation of the scaling relationship of mass and density of fractal objects, silica films can be prepared that show a variation in porosity (7--29 %) and refractive index (1.42--1.31) desired for applications in sensors, membranes, and photonics.

  4. Amorphous sol-gel insulating films

    SciTech Connect

    Brinker, C.J. New Mexico Univ., Albuquerque, NM . Center for Micro-Engineered Ceramics); Warren, W.L.; Logan, M.N.; Ashley, C.S. )

    1993-01-01

    The porosity of sol-gel thin films may be tailored for specific applications through control of the size and structure of inorganic polymers within the coating sol, the extent of polymer reaction and interpenetration during film formation, and the magnitude of the capillary pressure exerted during the final stage of drying. By maximizing the capillary pressure and avoiding excessive condensation, dense insulating films may be prepared as passivation layers on silicon substrates. Such films can exhibit excellent dielectric integrity, viz., low interface trap densities and insulating properties approaching those of thermally grown SiO[sub 2]. Alternatively, through exploitation of the scaling relationship of mass and density of fractal objects, silica films can be prepared that show a variation in porosity (7--29 %) and refractive index (1.42--1.31) desired for applications in sensors, membranes, and photonics.

  5. 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.

  6. 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.

  7. Opportunity's View on Sols 1803 and 1804

    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 1,803rd and 1,804th Martian days, or sols, of Opportunity's surface mission (Feb. 18 and 19, 2009). South is at the center; north at both ends.

    The rover had driven 55 meters on Sol 1803 before beginning to take the frames in this view. Tracks from that drive recede northward. 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.

  8. Stabilizer-free nanosized gold sols.

    PubMed

    Andreescu, Daniel; Sau, Tapan Kumar; Goia, Dan V

    2006-06-15

    The paper describes a convenient, rapid, and reproducible method for the synthesis of stable dispersions of uniform gold nanoparticles at ambient temperatures by mixing aqueous solutions of tetrachloroauric acid and iso-ascorbic acid. The influence of the experimental conditions on the size of the gold particles and the stability of the final sols was monitored by dynamic light scattering and UV-vis spectrophotometry. It was found that the size of the resulting nanoparticles is affected by the concentration and the pH of gold solution, while the stability of the electrostatically stabilized final sols is strongly dependent on the excess of reductant in the system, the ionic strength, and the temperature of the precipitation. Since the preparation process does not require the addition of a dispersing agent, the surface of the resulting gold nanoparticles can be easily functionalized to make them suitable for applications in medicine, biology, and catalysis.

  9. 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.

  10. PhysTrack’: a Matlab based environment for video tracking of kinematics in the physics laboratory

    NASA Astrophysics Data System (ADS)

    Umar Hassan, Muhammad; Sabieh Anwar, Muhammad

    2017-07-01

    In the past two decades, several computer software tools have been developed to investigate the motion of moving bodies in physics laboratories. In this article we report a Matlab based video tracking library, PhysTrack, primarily designed to investigate kinematics. We compare PhysTrack with other commonly available video tracking tools and outline its salient features. The general methodology of the whole video tracking process is described with a step by step explanation of several functionalities. Furthermore, results of some real physics experiments are also provided to demonstrate the working of the automated video tracking, data extraction, data analysis and presentation tools that come with this development environment. We believe that PhysTrack will be valuable for the large community of physics teachers and students already employing Matlab.

  11. 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.

  12. Toxoplasma gondii triggers phosphorylation and nuclear translocation of dendritic cell STAT1 while simultaneously blocking IFNγ-induced STAT1 transcriptional activity.

    PubMed

    Schneider, Anne G; Abi Abdallah, Delbert S; Butcher, Barbara A; Denkers, Eric Y

    2013-01-01

    The protozoan Toxoplasma gondii actively modulates cytokine-induced JAK/STAT signaling pathways to facilitate survival within the host, including blocking IFNγ-mediated STAT1-dependent proinflammatory gene expression. We sought to further characterize inhibition of STAT1 signaling in infected murine dendritic cells (DC) because this cell type has not previously been examined, yet is known to serve as an early target of in vivo infection. Unexpectedly, we discovered that T. gondii infection alone induced sustained STAT1 phosphorylation and nuclear translocation in DC in a parasite strain-independent manner. Maintenance of STAT1 phosphorylation required active invasion but intracellular parasite replication was dispensable. The parasite rhoptry protein ROP16, recently shown to mediate STAT3 and STAT6 phosphorylation, was not required for STAT1 phosphorylation. In combination with IFNγ, T. gondii induced synergistic STAT1 phosphorylation and binding of aberrant STAT1-containing complexes to IFNγ consensus sequence oligonucleotides. Despite these findings, parasite infection blocked STAT1 binding to the native promoters of the IFNγ-inducible genes Irf-1 and Lrg47, along with subsequent gene expression. These results reinforce the importance of parasite-mediated blockade of IFNγ responses in dendritic cells, while simultaneously showing that T. gondii alone induces STAT1 phosphorylation.

  13. 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.

  14. 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.

  15. 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.

  16. Panorama from Curiosity Sol 1000 Location Stereo

    NASA Image and Video Library

    2015-07-01

    This stereo view from the Navigation Camera (Navcam) on NASA's Curiosity Mars rover shows a 360-degree panorama around the location where the rover spent its 1,000th Martian day, or sol, on Mars. The image appears three-dimensional when viewed through red-blue glasses with the red lens on the left. Sol 1,000 of Curiosity's Mars-surface mission corresponded to May 30, 2015. The component images for this scene were taken on Sol 997 (May 27, 2015). The site is a valley just below "Marias Pass" on lower Mount Sharp. A map of the area is at http://mars.nasa.gov/msl/images/Curiosity_Location_Sol997-full.jpg. The center of the scene is toward the south, with north at both ends. This stereo view combines images from Navcam left-eye and right-eye cameras. A single-eye version of the scene is at PIA19679 . Tracks from the rover's drive to this site are visible at right. The rover team chose this location near Marias Pass because images from orbit showed what appeared to be a contact between two types of bedrock. The two types are evident in this panorama. The bedrock close to the rover is pale mudstone similar to what Curiosity examined in 2014 and early 2015 at "Pahrump Hills." The darker, finely bedded bedrock above it is sandstone that the rover team calls the "Stimson" unit. The largest-looking slab of Stimson sandstone in the image, in the lower left quadrant, is a target called "Ronan," selected for close-up inspection. on lower Mount Sharp. http://photojournal.jpl.nasa.gov/catalog/PIA19678

  17. 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.

  18. 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.

  19. 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.

  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. 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.

  2. Direct targets of pSTAT5 signalling in erythropoiesis

    PubMed Central

    Tuckey, Hugh; Magor, Graham W.; Perkins, Andrew C.

    2017-01-01

    Erythropoietin (EPO) acts through the dimeric erythropoietin receptor to stimulate proliferation, survival, differentiation and enucleation of erythroid progenitor cells. We undertook two complimentary approaches to find EPO-dependent pSTAT5 target genes in murine erythroid cells: RNA-seq of newly transcribed (4sU-labelled) RNA, and ChIP-seq for pSTAT5 30 minutes after EPO stimulation. We found 302 pSTAT5-occupied sites: ~15% of these reside in promoters while the rest reside within intronic enhancers or intergenic regions, some >100kb from the nearest TSS. The majority of pSTAT5 peaks contain a central palindromic GAS element, TTCYXRGAA. There was significant enrichment for GATA motifs and CACCC-box motifs within the neighbourhood of pSTAT5-bound peaks, and GATA1 and/or KLF1 co-occupancy at many sites. Using 4sU-RNA-seq we determined the EPO-induced transcriptome and validated differentially expressed genes using dynamic CAGE data and qRT-PCR. We identified known direct pSTAT5 target genes such as Bcl2l1, Pim1 and Cish, and many new targets likely to be involved in driving erythroid cell differentiation including those involved in mRNA splicing (Rbm25), epigenetic regulation (Suv420h2), and EpoR turnover (Clint1/EpsinR). Some of these new EpoR-JAK2-pSTAT5 target genes could be used as biomarkers for monitoring disease activity in polycythaemia vera, and for monitoring responses to JAK inhibitors. PMID:28732065

  3. 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

  4. STAT2/IRF9 directs a prolonged ISGF3-like transcriptional response and antiviral activity in the absence of STAT1

    PubMed Central

    Blaszczyk, Katarzyna; Olejnik, Adam; Nowicka, Hanna; Ozgyin, Lilla; Chen, Yi-Ling; Chmielewski, Stefan; Kostyrko, Kaja; Wesoly, Joanna; Balint, Balint Laszlo; Lee, Chien-Kuo; Bluyssen, Hans A.R.

    2015-01-01

    Evidence is accumulating for the existence of a signal transducer and activator of transcription 2 (STAT2)/interferon regulatory factor 9 (IRF9)-dependent, STAT1-independent interferon alpha (IFNα) signalling pathway. However, no detailed insight exists into the genome-wide transcriptional regulation and the biological implications of STAT2/IRF9-dependent IFNα signalling as compared with interferon-stimulated gene factor 3 (ISGF3). In STAT1-defeicient U3C cells stably overexpressing human STAT2 (hST2-U3C) and STAT1-deficient murine embryonic fibroblast cells stably overexpressing mouse STAT2 (mST2-MS1KO) we observed that the IFNα-induced expression of 2′-5′-oligoadenylate synthase 2 (OAS2) and interferon-induced protein with tetratricopeptide repeats 1 (Ifit1) correlated with the kinetics of STAT2 phosphorylation, and the presence of a STAT2/IRF9 complex requiring STAT2 phosphorylation and the STAT2 transactivation domain. Subsequent microarray analysis of IFNα-treated wild-type (WT) and STAT1 KO cells overexpressing STAT2 extended our observations and identified ∼120 known antiviral ISRE-containing interferon-stimulated genes (ISGs) commonly up-regulated by STAT2/IRF9 and ISGF3. The STAT2/IRF9-directed expression profile of these IFN-stimulated genes (ISGs) was prolonged as compared with the early and transient response mediated by ISGF3. In addition, we identified a group of ‘STAT2/IRF9-specific’ ISGs, whose response to IFNα was ISGF3-independent. Finally, STAT2/IRF9 was able to trigger an antiviral response upon encephalomyocarditis virus (EMCV) and vesicular stomatitis Indiana virus (VSV). Our results further prove that IFNα-activated STAT2/IRF9 induces a prolonged ISGF3-like transcriptome and generates an antiviral response in the absence of STAT1. Moreover, the existence of ‘STAT2/IRF9-specific’ target genes predicts a novel role of STAT2 in IFNα signalling. PMID:25564224

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Platinum states in citrate sols by EXAFS.

    PubMed

    Lin, Chia-Shiang; Khan, Maksudur R; Lin, Shawn D

    2005-07-01

    Platinum sols have been prepared by citrate reduction in the temperature range of 343-363 K. The Pt state in the solution was examined by EXAFS (extended X-ray absorption fine-structure spectroscopy). It did not show any PtPt bonding, a characteristic for reduced Pt sols. EXAFS model fitting further proved the presence of PtO with 4 oxygen neighbors, which suggests a tetraplanar coordination configuration. The possibility of neighboring Pt sharing oxygen ligand or the formation of PtO(x) is rejected by EXAFS model fitting. Citrate was found to be the most likely ligand to orient its oxygen end toward a charged Pt center. Thus we have revealed that the citrate treatment at this temperature range was clearly insufficient to reduce H2PtCl(6(aq)). Neither an extended period of reaction time nor an excess citrate reduced the Pt precursor. It is therefore highly recommended that the citrate sols should be carefully prepared and used.

  11. 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.

  12. 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.

  13. Erratum: Diffusive quantum criticality in three-dimensional disordered Dirac semimetals [Phys. Rev. B 90, 241112(R) (2014)

    NASA Astrophysics Data System (ADS)

    Roy, Bitan; Das Sarma, S.

    2016-03-01

    We correct erroneous conclusions from our previous article [Phys. Rev. B 90, 241112(R) (2014), 10.1103/PhysRevB.90.241112] regarding the values of various critical exponents, calculated to two-loop order. Furthermore, from a three-loop renormalization group flow equation, we argue, that ɛ -expansion near two spatial dimensions, with ɛ =d -2 , may not be reliable to address the critical properties of the disorder-driven Dirac semimetal-metal quantum phase transition in d =3 .

  14. 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.

  15. 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.

  16. Combined targeting of STAT3 and STAT5: a novel approach to overcome drug resistance in chronic myeloid leukemia.

    PubMed

    Gleixner, Karoline V; Schneeweiss, Mathias; Eisenwort, Gregor; Berger, Daniela; Herrmann, Harald; Blatt, Katharina; Greiner, Georg; Byrgazov, Konstantin; Hoermann, Gregor; Konopleva, Marina; Waliul, Islam; Cumaraswamy, Abbarna A; Gunning, Patrick T; Maeda, Hiroshi; Moriggl, Richard; Deininger, Michael; Lion, Thomas; Andreeff, Michael; Valent, Peter

    2017-09-01

    In chronic myeloid leukemia, resistance against BCR-ABL1 tyrosine kinase inhibitors can develop because of BCR-ABL1 mutations, activation of additional pro-oncogenic pathways, and stem cell resistance. Drug combinations covering a broad range of targets may overcome resistance. CDDO-Me (bardoxolone methyl) is a drug that inhibits the survival of leukemic cells by targeting different pro-survival molecules, including STAT3. We found that CDDO-Me inhibits proliferation and survival of tyrosine kinase inhibitor-resistant BCR-ABL1(+) cell lines and primary leukemic cells, including cells harboring BCR-ABL1(T315I) or T315I(+) compound mutations. Furthermore, CDDO-Me was found to block growth and survival of CD34(+)/CD38(-) leukemic stem cells (LSC). Moreover, CDDO-Me was found to produce synergistic growth-inhibitory effects when combined with BCR-ABL1 tyrosine kinase inhibitors. These drug-combinations were found to block multiple signaling cascades and molecules, including STAT3 and STAT5. Furthermore, combined targeting of STAT3 and STAT5 by shRNA and STAT5-targeting drugs also resulted in synergistic growth-inhibition, pointing to a new efficient concept of combinatorial STAT3 and STAT5 inhibition. However, CDDO-Me was also found to increase the expression of heme-oxygenase-1, a heat-shock-protein that triggers drug resistance and cell survival. We therefore combined CDDO-Me with the heme-oxygenase-1 inhibitor SMA-ZnPP, which also resulted in synergistic growth-inhibitory effects. Moreover, SMA-ZnPP was found to sensitize BCR-ABL1(+) cells against the combination 'CDDO-Me+ tyrosine kinase inhibitor'. Together, combined targeting of STAT3, STAT5, and heme-oxygenase-1 overcomes resistance in BCR-ABL1(+) cells, including stem cells and highly resistant sub-clones expressing BCR-ABL1(T315I) or T315I-compound mutations. Whether such drug-combinations are effective in tyrosine kinase inhibitor-resistant patients with chronic myeloid leukemia remains to be elucidated

  17. Toward a new STATe: the role of STATs in mitochondrial function.

    PubMed

    Meier, Jeremy A; Larner, Andrew C

    2014-02-01

    Signal Transducers and Activators of Transcription (STATs) have been studied extensively and have been associated with virtually every biochemical pathway. Until recently, however, they were thought to exert these effects solely as a nuclear transcription factor. The finding that STAT3 localizes to the mitochondria and modulates respiration has opened up a new avenue through which STATs may regulate the cell. Recently, other members of the STAT family (STAT1, STAT2, STAT5, and STAT6) have also been shown to be present in the mitochondria. Coordinate regulation at the nucleus and mitochondria by these proteins places them in a unique position to drive cellular processes to achieve a specific response. This review summarizes recent findings that have led to our current understanding of how STATs influence mitochondrial function in health and disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Toward a new STATe: The role of STATs in mitochondrial function

    PubMed Central

    Meier, Jeremy A.; Larner, Andrew C.

    2014-01-01

    Signal Transducers and Activators of Transcription (STATs) have been studied extensively and have been associated with virtually every biochemical pathway. Until recently, however, they were thought to exert these effects solely as a nuclear transcription factor. The finding that STAT3 localizes to the mitochondria and modulates respiration has opened up a new avenue through which STATs may regulate the cell. Recently, other members of the STAT family (STAT1, STAT2, STAT5, and STAT6) have also been shown to be present in the mitochondria. Coordinate regulation at the nucleus and mitochondria by these proteins places them in a unique position to drive cellular processes to achieve a specific response. This review summarizes recent findings that have led to our current understanding of how STATs influence mitochondrial function in health and disease. PMID:24434063

  19. Structural analysis of the STAT1-STAT2 heterodimer revealed the mechanism of Sendai virus C protein-mediated blockade of type 1 interferon signaling.

    PubMed

    Oda, Kosuke; Oda, Takashi; Matoba, Yasuyuki; Sato, Mamoru; Irie, Takashi; Sakaguchi, Takemasa

    2017-10-04

    Sendai virus (SeV), which causes respiratory diseases in rodents, possesses the C protein that blocks the signal transduction of interferon (IFN), thereby escaping from host innate immunity. We previously demonstrated by using protein crystallography that two molecules of Y3 (C-terminal half of C protein) can bind to the homodimer of the N-terminal domain of STAT1 (STAT1ND), elucidating the mechanism of inhibition of IFN-γ signal transduction. SeV C protein also blocks the signal transduction of IFN-α/β by inhibiting the phosphorylation of STAT1 and STAT2, although the mechanism for the inhibition is unclear. Therefore, we sought to elucidate the mechanism of inhibition of IFN-signal transduction via STAT1 and STAT2. Small angle X-ray scattering (SAXS) analysis indicated that STAT1ND associates with the N-terminal domain of STAT2 (STAT2ND) with the help of a Gly-rich linker. We generated a linker-less recombinant protein possessing a STAT1ND:STAT2ND heterodimeric structure via an artificial disulfide bond. Analytical size-exclusion chromatography and surface plasmon resonance revealed that one molecule of Y3 can associate with a linker-less recombinant protein. We propose that one molecule of C protein associates with the STAT1:STAT2 heterodimer, inducing a conformational change to an antiparallel form, which is easily dephosphorylated. This suggests that association of C protein with the STAT1ND-STAT2ND heterodimer is an important factor to block the IFN-α/β signal transduction. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  20. 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.

  1. 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

  2. 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.

  3. Human Cytomegalovirus IE1 Protein Disrupts Interleukin-6 Signaling by Sequestering STAT3 in the Nucleus

    PubMed Central

    Reitsma, Justin M.; Sato, Hiromi; Nevels, Michael

    2013-01-01

    In the canonical STAT3 signaling pathway, binding of agonist to receptors activates Janus kinases that phosphorylate cytoplasmic STAT3 at tyrosine 705 (Y705). Phosphorylated STAT3 dimers accumulate in the nucleus and drive the expression of genes involved in inflammation, angiogenesis, invasion, and proliferation. Here, we demonstrate that human cytomegalovirus (HCMV) infection rapidly promotes nuclear localization of STAT3 in the absence of robust phosphorylation at Y705. Furthermore, infection disrupts interleukin-6 (IL-6)-induced phosphorylation of STAT3 and expression of a subset of IL-6-induced STAT3-regulated genes, including SOCS3. We show that the HCMV 72-kDa immediate-early 1 (IE1) protein associates with STAT3 and is necessary to localize STAT3 to the nucleus during infection. Furthermore, expression of IE1 is sufficient to disrupt IL-6-induced phosphorylation of STAT3, binding of STAT3 to the SOCS3 promoter, and SOCS3 gene expression. Finally, inhibition of STAT3 nuclear localization or STAT3 expression during infection is linked to diminished HCMV genome replication. Viral gene expression is also disrupted, with the greatest impact seen following viral DNA synthesis. Our study identifies IE1 as a new regulator of STAT3 intracellular localization and IL-6 signaling and points to an unanticipated role of STAT3 in HCMV infection. PMID:23903834

  4. Insulin stimulates the serine phosphorylation of the signal transducer and activator of transcription (STAT3) isoform.

    PubMed

    Ceresa, B P; Pessin, J E

    1996-05-24

    Insulin stimulation of Chinese hamster ovary cells expressing the human insulin receptor and differentiated 3T3L1 adipocytes resulted in a time-dependent reduction in the SDS-polyacrylamide gel electrophoretic mobility of STAT3. The decreased STAT3 mobility initially occurred by 2 min and was quantitative by 5 min. In addition, the change in STAT3 mobility was concentration-dependent and was detectable at 0.3 nm insulin with maximal effect between 1 and 3 nm. Although both these cell types also express the STAT1 alpha, STAT1 beta, STAT5, and STAT6 isoforms, only STAT3 was observed to undergo an insulin-dependent reduction in mobility. Immuno-precipitation of STAT1 and STAT3 from 32P-labeled cells demonstrated that only STAT3 was phosphorylated in response to insulin whereas phosphoamino acid analysis indicated that this phosphorylation event occurred exclusively on serine residues. Furthermore, treatment of cell extracts with alkaline phosphatase reversed the insulin-stimulated decrease in STAT3 mobility. Together, these data demonstrate that insulin is a specific activator of STAT3 serine phosphorylation without affecting the other STAT isoforms.

  5. Sol concentration effect on ZnO nanofibers photocatalytic activity synthesized by sol-gel dip coating method

    NASA Astrophysics Data System (ADS)

    Toubane, M.; Tala-Ighil, R.; Bensouici, F.; Bououdina, M.; Souier, M.; Liu, S.; Cai, W.; Iratni, A.

    2017-03-01

    ZnO thin films were deposited onto glass substrate by sol-gel dip coating method. The initial sol concentrations were varied from 0.2 to 0.5 M. Zinc acetate dihydrate, ethanol and Diethanolamine (DEA) were used as staring material, solvent and stabilizer respectively. The evolution of structural, optical properties and methylene blue (MB) photodegradation of the as-deposited films on sol concentration was investigated. Rietveld refinements of x-ray patterns reveal that all the as-prepared thin films have a Zincite-type structure with grain orientation along to c-axis. The strongest sol concentration is favorable for the highest crystallization quality. However, the high preferred orientation factor (POF) occurs for 0.3 M sol concentration. The field emission scanning electron microscopy observations reveals nanofibrous morphology with different lengths. The nanofibers density increases with increasing sols concentrations until forming a flower-like morphology. The EDS analysis confirms the high purity of the as-deposited ZnO films. It is found that all films present good transparency greater than 95% in the visible range; the optical band gap is slightly reduced with the increase in sol concentration. The photocatalytic degradation is enhanced by 90% with the sol concentration. The K app rate reaction increased with increasing sol concentration. The films stability is found to slightly decrease after the third cycle, especially for 0.5 M sol concentration.

  6. 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.

  7. 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.

  8. 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

  9. Targeting STAT3 with silibinin to improve cancer therapeutics.

    PubMed

    Bosch-Barrera, Joaquim; Queralt, Bernardo; Menendez, Javier A

    2017-07-01

    Signal transducer and activator of transcription 3 (STAT3) has a prominent role in mediating resistance to conventional chemo-/radio-therapies and modern targeted drugs. While a number of STAT3 inhibitors have been shown to enhance the efficacy of therapeutic agents in vitro, the majority of them have yet to enter clinical evaluation mostly because of lack of efficacy issues. Silibinin is the main component of the silymarin complex, a standardized extract obtained from the seeds of the milk thistle herb Silybum marianum. This review summarizes current evidence supporting the ability of silibinin to function as a natural down-modulator of STAT3 activity. We examine the reported capacity of silibinin to reduce the toxicity of cancer treatments and to reverse tumor cell resistance via STAT3 inhibition. We also briefly review our clinical data in cancer patients treated with oral nutraceutical products containing silibinin. The beneficial effects of silibinin might accelerate the design of strategies aimed to overcome and prevent the emergence of STAT3-mediated cancer drug resistance in clinical settings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Stat3 as a potential therapeutic target for rheumatoid arthritis.

    PubMed

    Oike, Takatsugu; Sato, Yuiko; Kobayashi, Tami; Miyamoto, Kana; Nakamura, Satoshi; Kaneko, Yosuke; Kobayashi, Shu; Harato, Kengo; Saya, Hideyuki; Matsumoto, Morio; Nakamura, Masaya; Niki, Yasuo; Miyamoto, Takeshi

    2017-09-08

    Rheumatoid arthritis (RA) is a multi-factorial disease characterized by chronic inflammation and destruction of multiple joints. To date, various biologic treatments for RA such as anti-tumor necrosis factor alpha antibodies have been developed; however, mechanisms underlying RA development remain unclear and targeted therapy for this condition has not been established. Here, we provide evidence that signal transducer and activator of transcription 3 (Stat3) promotes inflammation and joint erosion in a mouse model of arthritis. Stat3 global KO mice show early embryonic lethality; thus, we generated viable Stat3 conditional knockout adult mice and found that they were significantly resistant to collagen-induced arthritis (CIA), the most common RA model, compared with controls. We then used an in vitro culture system to screen ninety-six existing drugs to select Stat3 inhibitors and selected five candidate inhibitors. Among them, three significantly inhibited development of arthritis and joint erosion in CIA wild-type mice. These findings suggest that Stat3 inhibitors may serve as promising drugs for RA therapy.

  11. [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

  12. Bioactive materials for biomedical applications using sol-gel technology.

    PubMed

    Gupta, Radha; Kumar, Ashok

    2008-09-01

    This review paper focuses on the sol-gel technology that has been applied in many of the potential research areas and highlights the importance of sol-gel technology for preparing bioactive materials for biomedical applications. The versatility of sol-gel chemistry enables us to manipulate the characteristics of material required for particular applications. Sol-gel derived materials have proved to be good biomaterials for coating films and for the construction of super-paramagnetic nanoparticles, bioactive glasses and fiberoptic applicators for various biomedical applications. The introduction of the sol-gel route in a conventional method of preparing implants improves the mechanical strength, biocompatibility and bioactivity of scaffolds and prevents corrosion of metallic implants. The use of organically modified silanes (ORMOSILS) yields flexible and bioactive materials for soft and hard tissue replacement. A novel approach of nitric-oxide-releasing sol-gels as antibacterial coatings for reducing the infection around orthopedic implants has also been discussed.

  13. Superhydrophobic sol-gel nanocomposite coatings with enhanced hardness

    NASA Astrophysics Data System (ADS)

    Lakshmi, R. V.; Bharathidasan, T.; Basu, Bharathibai J.

    2011-10-01

    Sol-gel superhydrophobic coatings with improved hardness were prepared by embedding fumed silica nanoparticles in a partially condensed hybrid sol of methyltriethoxysilane (MTEOS) and colloidal silica. Fumed silica particles of size 25-30 nm were incorporated in the sol and the mixture was spray-coated on glass substrate. Water contact angle (WCA) of the composite coating increased with increase in silica content of the sol mixture. The concentration of silica in the sol mixture was optimized to obtain robust superhydrophobic coatings with a WCA of 162.5° and a pencil hardness of 5H. The wetting state of water droplet on the sol-gel composite coatings was analysed with both Wenzel and Cassie-Baxter models.

  14. Organically modified sols as pseudostationary phases for microchip electrophoresis.

    PubMed

    Pumera, Martin; Wang, Joseph; Grushka, Eli; Lev, Ovadia

    2007-04-30

    We demonstrate that the selectivity of microchip electrophoresis separations is greatly improved by the presence of organically modified silica (Ormosil) sols in the run buffer. A negatively-charged N-(trimethoxysilylpropyl)ethylenediamine triacetic-acid (TETT)-based sol is used for improving the selectivity between nitroaromatic explosives and a methyltrimethoxysilane (MTMOS)-based sol is employed for enhancing the microchip separation of environmental pollutants, aminophenols. These sols are added to the run buffer and act as pseudostationary phases. Their presence in the run buffer changes the apparent mobility of studied solutes, and leads to a higher resolution. The observed mobilities changes reflect the interactions between the Ormosil sols and the solutes. Relevant experimental variables have been characterized and optimized. The diverse chemistry of Ormosil sols should be extremely useful for tailoring the selectivity of a wide range of electrophoresis microchip separations.

  15. Comment on a paper by Alain J. Phares and Francis J. Wunderlich [J. Math. Phys. 26, 2491 (1985)

    NASA Astrophysics Data System (ADS)

    Wheeler, John C.

    1987-11-01

    The claim of Phares and Wunderlich [J. Math. Phys. 26, 2491 (1985)] to have obtained the exact closed form analytic solution to the problem of dimers on infinite two- and three-dimensional lattices is shown to be incorrect. Their expressions do not agree with exact expansions obtained by virial and lattice counting methods.

  16. 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.

  17. 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)

  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. 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.

  20. The analysis of senior high school students' physics HOTS in Bantul District measured using PhysReMChoTHOTS

    NASA Astrophysics Data System (ADS)

    Istiyono, Edi

    2017-08-01

    The purpose of this research is to describe the results of higher order thinking skills in physics (PhysHOTS) measurement including: (1) percentage of PhysHOTS level and (2) percentage of the domination of response in the category of students in each analyzing, evaluating, and creating skill. There were 404 10th grade students in Bantul District as the respondents of this research. The instrument used for measurement was PhysReMChoTHOTS. It was divided into two sets consisting of 44 items and including 8 anchor items stated valid by a Physicist, Physics Education Expert, and Physics Education Measurement Expert. The instrument was fit to PCM. The reliability coefficient of this test is 0.71, while the difficulty index of the items ranges from -0.61 to 0.51. The results of the measurement show that: (1) The percentage of each category of PhysHOTS for the 10th grade students in Bantul District for the very low, low, medium, high, and very high category is 4.75 %, 40.30 %, 33.45 %, 19.50 %, and 2.00 %, respectively; and (2) The order in analyzing skills, starts from the weakest, is attributing, differentiating and organizing. The order in evaluating skills, starts from the weakest, is critiquing and checking. Meanwhile, the order in creating skills, starts from the weakest, is producing, planning, and generating.

  1. 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.

  2. 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.

  3. 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.

  4. 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)

  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. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. Functions of the Drosophila JAK-STAT pathway

    PubMed Central

    Amoyel, Marc; Bach, Erika A.

    2012-01-01

    JAK-STAT signaling has been proposed to act in numerous stem cells in a variety of organisms. Here we provide an overview of its roles in three well characterized stem cell populations in Drosophila, in the intestine, lymph gland and testis. In flies, there is a single JAK and a single STAT, which has made the genetic dissection of pathway function considerably easier and facilitated the analysis of communication between stem cells, their niches and offspring. Studies in flies have revealed roles for this pathway as diverse as regulating bona fide intrinsic self-renewal, integrating response to environmental cues that control quiescence and promoting mitogenic responses to stress. PMID:24058767

  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. Structural and functional studies of STAT1 from Atlantic salmon (Salmo salar)

    PubMed Central

    2010-01-01

    Background Type I and type II interferons (IFNs) exert their effects mainly through the JAK/STAT pathway, which is presently best described in mammals. STAT1 is involved in signaling pathways induced by both types of IFNs. It has a domain-like structure including an amino-terminus that stabilizes interaction between STAT dimers in a promoter-binding situation, a coiled coil domain facilitating interactions to other proteins, a central DNA-binding domain, a SH2 domain responsible for dimerization of phosphorylated STATs and conserved phosphorylation sites within the carboxy terminus. The latter is also the transcriptional activation domain. Results A salmon (Salmo salar) STAT1 homologue, named ssSTAT1a, has been identified and was shown to be ubiquitously expressed in various cells and tissues. The ssSTAT1a had a domain-like structure with functional motifs that are similar to higher vertebrates. Endogenous STAT1 was shown to be phosphorylated at tyrosine residues both in salmon leukocytes and in TO cells treated with recombinant type I and type II IFNs. Also ectopically expressed ssSTAT1 was phosphorylated in salmon cells upon in vitro stimulation by the IFNs, confirming that the cloned gene was recognized by upstream tyrosine kinases. Treatment with IFNs led to nuclear translocation of STAT1 within one hour. The ability of salmon STAT1 to dimerize was also shown. Conclusions The structural and functional properties of salmon STAT1 resemble the properties of mammalian STAT1. PMID:20353564

  16. Loss of STAT3 in Lymphoma Relaxes NK Cell-Mediated Tumor Surveillance.

    PubMed

    Putz, Eva Maria; Hoelzl, Maria Agnes; Baeck, Julia; Bago-Horvath, Zsuzsanna; Schuster, Christian; Reichholf, Brian; Kern, Daniela; Aberger, Fritz; Sexl, Veronika; Hoelbl-Kovacic, Andrea

    2014-01-27

    The transcription factors and proto-oncogenes STAT3 and STAT5 are highly activated in hematological malignancies and represent promising therapeutic targets. Whereas the importance of STAT5 as tumor promoter is beyond doubt, the role of STAT3 in hematological cancers is less well understood. Both, enforced as well as attenuated expression of STAT3 were reported in hematopoietic malignancies. Recent evidence implicates STAT3 as key player for tumor immune surveillance as it both mediates the production of and response to inflammatory cytokines. Here we investigated the effects of STAT3 deletion in a BCR/ABL-induced lymphoma model, which is tightly controlled by natural killer (NK) cells in vivo. Upon STAT3 deletion tumor growth is significantly enhanced when compared to STAT3-expressing controls. The increased tumor size upon loss of STAT3 was accompanied by reduced NK cell infiltration and decreased levels of the cytokine IFN-γ and the chemokine RANTES. Upon transplantation into NK cell-deficient mice differences in lymphoma size were abolished indicating that STAT3 expression in the tumor cells controls NK cell-dependent tumor surveillance. Our findings indicate that STAT3 inhibition in lymphoma patients will impair NK cell-mediated tumor surveillance, which needs to be taken into account when testing STAT3 inhibitors in preclinical or clinical trials.

  17. The expression and regulation of STATs during 3T3-L1 adipocyte differentiation.

    PubMed

    Stephens, J M; Morrison, R F; Pilch, P F

    1996-05-03

    STATs (Signal Transducers and Activators of Transcription) comprise a family of transcription factors that reside in the cytoplasm of resting cells. In response to a variety of stimuli, STATs become tyrosine-phosphorylated and translocate to the nucleus where they mediate transcriptional regulation. We have used the 3T3-L1 murine cell line to examine the expression of STAT proteins as a function of their differentiation into adipocytes. The expression of STATs 1, 3, and 5, but not of STAT 6, is markedly elevated in adipocytes as compared with their fibroblast precursors. Exposure of 3T3-L1 preadipocytes to tumor necrosis factor alpha (TNF alpha) blocks their differentiation into adipocytes. Therefore, we examined STAT expression as a function of differentiation in the presence of this cytokine. The expression of STATs 1 and 5 is markedly attenuated in the presence of TNF alpha, whereas STAT 3 expression is unaffected by this treatment. Only STAT 1 is down-regulated by TNF alpha in fully differentiated cells. Thus, although the expression of STATs 1, 3, and 5 is markedly enhanced upon differentiation, only STAT 5 expression is tightly correlated with the adipocyte phenotype. These data suggest that STAT 5, and possibly STAT 1, could be potential inducers of tissue-specific genes, which contribute to the development and maintenance of the adipocyte phenotype.

  18. 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.

  19. '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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Spirit's View on Sol 107 (vertical)

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This vertical projection was assembled from images taken by the navigation camera on the Mars Exploration Rover Spirit on sol 107 (April 21, 2004) at a region dubbed 'site 32.' Spirit is sitting east of 'Missoula Crater,' no longer in the crater's ejecta field, but on outer plains. Since landing, Spirit has traveled almost exclusively over ejecta fields. This new landscape looks different with fewer angular rocks and more rounded, vesicle-filled rocks. Spirit will continue another 1,900 meters (1.18 miles) along this terrain before reaching the western base of the 'Columbia Hills.'

  7. Spirit's View on Sol 107 (polar)

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This polar projection was assembled from images taken by the navigation camera on the Mars Exploration Rover Spirit on sol 107 (April 21, 2004) at a region dubbed 'site 32.' Spirit is sitting east of 'Missoula Crater,' no longer in the crater's ejecta field, but on outer plains. Since landing, Spirit has traveled almost exclusively over ejecta fields. This new landscape looks different with fewer angular rocks and more rounded, vesicle-filled rocks. Spirit will continue another 1,900 meters (1.18 miles) along this terrain before reaching the western base of the 'Columbia Hills.'

  8. Preparation of counterion stabilized concentrated silver sols.

    PubMed

    LaPlante, Sylas; Halaciuga, Ionel; Goia, Dan V

    2011-07-01

    A strategy for obtaining stable concentrated silver dispersions without dedicated stabilizing agents is presented. This approach consists of rapidly mixing aqueous solutions of silver salicylate and ascorbic acid. By using salicylate as Ag(+) counterion, it is possible to prepare stable sols with metal concentrations up to two orders of magnitude higher than with silver nitrate. The stabilizing effect of the counterion is the result of a decreased ionic strength due to salicylate protonation and its adsorption on the surface of silver. Both effects increase the range of the electrostatic repulsive forces by expanding the electrical double layer. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Two Domains of the V Protein of Virulent Canine Distemper Virus Selectively Inhibit STAT1 and STAT2 Nuclear Import▿

    PubMed Central

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

    2010-01-01

    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-α/β)-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-α/β-mediated signaling. Importantly, immunofluorescence analysis illustrated that the inhibition of IFN-α/β-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-α/β-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-α/β-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-α/β-mediated signaling. Hence, our experiments reveal a novel mechanism of IFN-α/β evasion among the morbilliviruses. PMID:20427537

  10. 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.

  11. 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.

  12. Identification and functional evaluation of two STAT3 variants in grass carp: Implication for the existence of specific alternative splicing of STAT3 gene in teleost.

    PubMed

    Du, Linyong; Zhou, Hong; Qin, Lei; Wei, He; Zhang, Anying; Yang, Kun; Wang, Xinyan

    2017-11-01

    A STAT family member, STAT3, becomes activated as a DNA binding protein in response to cytokines and growth factors. In teleost, STAT3 cDNA has been cloned and identified in a few species, but only a single STAT3 transcript is revealed in these studies. In the present study, two variants of STAT3 gene generated by alternative splicing were isolated from grass carp and nominated as STAT3α1 and STAT3α2 based on the homology with their mammalian orthologs. In particular, the homologs of STAT3α1/2 were also found in various fish species, including zebrafish, takifugu, tilapia, medaka and goldfish. Intriguingly, sequence alignment and genomic structure analysis revealed that fish STAT3α1/2 are generated through similar alternative splicing events, implying the potential physiological significance of generating STAT3 variants in fish. Grass carp STAT3α1/2 (gcSTAT3α1/2) were ubiquitously expressed although the transcript levels of STAT3α2 were markedly higher than STAT3α1 in all examined tissues. In vivo and in vitro studies showed that the expression patterns of these two variants were similar under the stimulation of immune stimuli. To reveal the role of gcSTAT3α1/2 in fish immunity, their phosphorylation and involvement in IL-17A/F1 mRNA expression were demonstrated in grass carp peripheral blood lymphocytes upon LPS or PHA challenge, providing evidence for the functional conservation of STAT3 signaling in fish. These findings also raise a question of whether both gcSTAT3α1/2 participate in transcriptional regulation in fish. Actually, our results showed that both of them had the ability to translocate into the nucleus upon activation, and to amplify IL-10 signaling, indicating the existence of STAT3 isoforms with functional redundancy in teleost. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. The JAK2 Inhibitor, AZD1480, Potently Blocks Stat3 Signaling and Oncogenesis in Solid Tumors

    PubMed Central

    Hedvat, Michael; Huszar, Dennis; Herrmann, Andreas; Gozgit, Joseph M.; Schroeder, Anne; Sheehy, Adam; Buettner, Ralf; Proia, David; Kowolik, Claudia M.; Xin, Hong; Armstrong, Brian; Bebernitz, Geraldine; Weng, Shaobu; Wang, Lin; Ye, Minwei; McEachern, Kristen; Chen, Huawei; Morosini, Deborah; Bell, Kirsten; Alimzhanov, Marat; Ioannidis, Stephanos; McCoon, Patricia; Cao, Zhu A.; Yu, Hua; Jove, Richard; Zinda, Michael

    2009-01-01

    Summary Persistent activation of Stat3 is oncogenic and is prevalent in a wide variety of human cancers. Chronic cytokine stimulation is associated with Stat3 activation in some tumors, implicating cytokine receptor-associated Jak family kinases. Using Jak2 inhibitors, we demonstrate a central role of Jaks in modulating basal and cytokine-induced Stat3 activation in human solid tumor cell lines. Inhibition of Jak2 activity is associated with abrogation of Stat3 nuclear translocation and tumorigenesis. The Jak2 inhibitor, AZD1480, suppresses the growth of human solid tumor xenografts harboring persistent Stat3 activity. We demonstrate the essential role of Stat3 downstream of Jaks by inhibition of tumor growth using shRNA targeting Stat3. Our data support a key role of Jak kinase activity in Stat3-dependent tumorigenesis. PMID:19962667

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. IL-26 promotes the proliferation and survival of human gastric cancer cells by regulating the balance of STAT1 and STAT3 activation.

    PubMed

    You, Wei; Tang, Qiyun; Zhang, Chuanyong; Wu, Jindao; Gu, Chunrong; Wu, Zhengshan; Li, Xiangcheng

    2013-01-01

    Interleukin-26 (IL-26) is one of the cytokines secreted by Th17 cells whose role in human tumors remains unknown. Here, we investigated the expression and potential role of IL-26 in human gastric cancer (GC). The expression of IL-26 and related molecules such as IL-20R1, STAT1 and STAT3 was examined by real-time PCR and immunohistochemisty. The effects of IL-26 on cell proliferation and cisplatin-induced apoptosis were analyzed by BrdU cooperation assay and PI-Annexin V co-staining, respectively. Lentiviral mediated siRNA was used to explore its mechanism of action, and IL-26 related signaling was analyzed by western blotting. Human GC tissues showed increased levels of IL-26 and its related molecules and activation of STAT3 signaling, whereas STAT1 activation did not differ significantly between GC and normal gastric tissues. Moreover, IL-26 was primarily produced by Th17 and NK cells. IL-26 promoted the proliferation and survival of MKN45 and SGC-7901 gastric cancer cells in a dose-dependent manner. Furthermore, IL-20R2 and IL-10R1, which are two essential receptors for IL-26 signaling, were expressed in both cell lines. IL-26 activated STAT1 and STAT3 signaling; however, the upregulation of the expression of Bcl-2, Bcl-xl and c-myc indicated that the effect of IL-26 is mediated by STAT3 activation. Knockdown of STAT1 and STAT3 expression suggested that the proliferative and anti-apoptotic effects of IL-26 are mediated by the modulation of STAT1/STAT3 activation. In summary, elevated levels of IL-26 in human GC promote proliferation and survival by modulating STAT1/STAT3 signaling.

  19. 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.

  20. 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

  1. Novel Multiplexed Assay for Identifying SH2 Domain Antagonists of STAT Family Proteins

    PubMed Central

    Takakuma, Kazuyuki; Ogo, Naohisa; Uehara, Yutaka; Takahashi, Susumu; Miyoshi, Nao; Asai, Akira

    2013-01-01

    Some of the signal transducer and activator of transcription (STAT) family members are constitutively activated in a wide variety of human tumors. The activity of STAT depends on their Src homology 2 (SH2) domain-mediated binding to sequences containing phosphorylated tyrosine. Thus, antagonizing this binding is a feasible approach to inhibiting STAT activation. We have developed a novel multiplexed assay for STAT3- and STAT5b-SH2 binding, based on amplified luminescent proximity homogeneous assay (Alpha) technology. AlphaLISA and AlphaScreen beads were combined in a single-well assay, which allowed the binding of STAT3- and STAT5b-SH2 to phosphotyrosine peptides to be simultaneously monitored. Biotin-labeled recombinant human STAT proteins were obtained as N- and C-terminal deletion mutants. The spacer length of the DIG-labeled peptide, the reaction time, and the concentration of sodium chloride were optimized to establish a HTS system with Z’ values of greater than 0.6 for both STAT3- and STAT5b-SH2 binding. We performed a HTS campaign for chemical libraries using this multiplexed assay and identified hit compounds. A 2-chloro-1,4-naphthalenedione derivative, Compound 1, preferentially inhibited STAT3-SH2 binding in vitro, and the nuclear translocation of STAT3 in HeLa cells. Initial structure activity relationship (SAR) studies using the multiplexed assay showed the 3-substituent effect on both the activity and selectivity of STAT3 and STAT5b inhibition. Therefore, this multiplexed assay is useful for not only searching for potential lead compounds but also obtaining SAR data for developing new STAT3/STAT5b inhibitors. PMID:23977103

  2. 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.

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

    PubMed

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

    2016-07-26

    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.

  4. 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##

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. The Martian dust storm of Sol 1742

    NASA Astrophysics Data System (ADS)

    Moore, H. J.

    1985-11-01

    After nearly five earth years on Mars, the Mutch Memorial Station (Viking Lander 1) finally witnessed a local dust storm that eroded trenches, conical piles, and other disturbed surfaces in the sample field and near the Lander. The event, called the Dust Storm of Sol 1742, occurred late in the third winter of Lander observations between Sols 1728 and 1757. Analyses of tiny new wind tails and movement of materials indicate that the eroding winds were variable but northeasterly than those that had previously shaped the surface. Pebbly residues and movement of 4-5 mm clods suggest drag velocities or friction speeds of the winds were about 2.2-4.0 m/s. Wind speeds at the height of the meteorology boom (1.6 m) were probably about 40-50 m/s. Much of the observed erosion could have occurred in a few to several tens of seconds, but somewhat longer times are suggested by analogy with the erosion of terrestrial soils. Most of the erosion occurred where preexisting equilibrium conditions of surface configurations and surface material properties had been altered by the Lander during landing and during surface-sampler activities, but thin layers of bright fine-grained dust were also removed and redistributed. Surfaces where preexisting equilibrium conditions were unaltered appeared to be uneroded.

  10. Clouds over 'Endurance' on Sol 291

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Clouds appear in the martian sky above 'Endurance Crater' in this mosaic of frames taken by the navigation camera on NASA's Mars Exploration Rover Opportunity during the morning of the rover's 291st sol (Nov. 17, 2004). The view spans an arc from the east on the left to the southwest on the right.

    Opportunity has observed differences in cloudiness from one sol to the next, a reminder that Mars, like Earth, has daily weather as well as longer-term seasonal changes.

    The images that are combined to produce this view have been processed to remove geometrical distortion associated with the camera's 45-degree field of view. In addition, special image processing has been applied to the original images to enhance the clouds and make them visible across the entire mosaic. Glare from the Sun washed out the clouds on the left in the original images; this glare was removed. The left-most image in this mosaic contains some artifacts from pointing the camera toward the Sun. The rim of Endurance has been processed separately and merged back with the sky to better show the context.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  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. 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.

  7. Safe and Environmentally Acceptable Sol-Gel-Derived Pyrophoric Pyrotechnics

    DTIC Science & Technology

    2004-07-01

    i Final Report 2003 Safe and Environmentally Acceptable Sol-Gel-Derived Pyrophoric Pyrotechnics PP-1276 Lawrence Livermore...REPORT TYPE Final 3. DATES COVERED - 4. TITLE AND SUBTITLE Safe and Environmentally Acceptable Sol-Gel-Derived Pyrophoric Pyrotechnics 5a...Background Pyrotechnics can be grouped into six families; decoy flares, illuminating flares, colored flares, smokes, igniters/starters and

  8. 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…

  9. 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…

  10. 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)].

  11. Comment on ``Equation of state of aluminum nitride and its shock response'' [J. Appl. Phys. 76, 4077 (1994)

    NASA Astrophysics Data System (ADS)

    Rosenberg, Z.; Brar, N. S.

    1995-11-01

    A recent article by Dandekar, Abbate, and Frankel [J. Appl. Phys. 76, 4077 (1994)] reviews existing data on high-pressure properties of aluminum nitride (AlN) in an effort to build an equation of state for this material. A rather large portion of that article is devoted to the shear strength of AlN and, in particular, to our data of 1991 with longitudinal and lateral stress gauges [Z. Rosenberg, N. S. Brar, and S. J. Bless, J. Appl. Phys. 70, 167 (1991)]. Since our highest data point has an error of 1 GPa, much of the discussion and conclusions of Dandekar and co-workers are not relevant once this error in data reduction is corrected. We also discuss the relevance of our shear strength data for various issues, such as the phase transformation of AlN at 20 GPa and the general shape of Hugoniot curves for brittle solids.

  12. 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)].

  13. Methotrexate Is a JAK/STAT Pathway Inhibitor.

    PubMed

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

    2015-01-01

    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. 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. 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-dose methotrexate. In addition, we

  14. 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

  15. 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

  16. 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.

  17. STAT4 deficiency reduces obesity-induced insulin resistance and adipose tissue inflammation.

    PubMed

    Dobrian, Anca D; Galkina, Elena V; Ma, Qian; Hatcher, Margaret; Aye, Sabai Myo; Butcher, Mathew J; Ma, Kaiwen; Haynes, Bronson A; Kaplan, Mark H; Nadler, Jerry L

    2013-12-01

    Signal transducer and activator of transcription (STAT) 4 is one of the seven members of the STAT family. STAT4 has a prominent role in mediating interleukin-12-induced T-helper cell type 1 lineage differentiation. T cells are key players in the maintenance of adipose tissue (AT) inflammation. The role of STAT4 in obesity and AT inflammation is unknown. We sought to determine the role of STAT4 in AT inflammation in obesity-induced insulin resistance. We studied STAT4-null mice on the C57Bl6/J background. We have found that STAT4(-/-)C57Bl6/J mice develop high-fat diet-induced obesity (DIO) similar to wild-type controls, but that they have significantly improved insulin sensitivity and better glucose tolerance. Using flow cytometry and real-time PCR, we show that STAT4(-/-) mice with DIO produce significantly reduced numbers of inflammatory cytokines and chemokines in adipocytes, have reduced numbers of CD8(+) cells, and display increased alternative (M2) macrophage polarization. CD8(+) cells, but not CD4(+) cells, from STAT4(-/-) mice displayed reduced in vitro migration. Also, we found that adipocyte inflammation is reduced and insulin signaling is improved in STAT4(-/-) mice with DIO. We have identified STAT4 as a key contributor to insulin resistance and AT inflammation in DIO. Targeting STAT4 activation could be a novel approach to reducing AT inflammation and insulin resistance in obesity.

  18. Technologies for Genome-Wide Identification of Stat5 Regulated Genes

    DTIC Science & Technology

    2003-01-01

    37 Role of Prl- Jak2 -Stat5 Signaling in Mammary Physiology.......................................... 39 Clinical Implications of Stat5...ROLE OF PRL- JAK2 -STAT5 SIGNALING IN MAMMARY EPITHELIAL CELL DIFFERENTIATION AND GROWTH...Differentiation of HC11 Mouse Mammary Epithelial Cells Correlated With Activation of Tyrosine Kinase Jak2

  19. 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.

  20. Comment on: “Exposed-key weakness of αη” [Phys. Lett. A 370 (2007) 131

    NASA Astrophysics Data System (ADS)

    Nair, Ranjith; Yuen, Horace P.

    2008-11-01

    We show that the insecurity claim of the αη cryptosystem made by C. Ahn and K. Birnbaum in [C. Ahn, K. Birnbaum, Phys. Lett. A 370 (2007) 131] under heterodyne attack is based on invalid extrapolations of Shannon's random cipher analysis and on an invalid statistical independence assumption. We show, both for standard ciphers and αη, that expressions of the kind given by Ahn and Birnbaum can at best be interpreted as security lower bounds.

  1. Comment on "The thermodynamical instability induced by pressure ionization in fluid helium" [Phys. Plasmas 23, 112709 (2016)

    NASA Astrophysics Data System (ADS)

    Quan, W. L.

    2017-06-01

    In a recent paper, Li et al. [Phys. Plasmas 23, 112709 (2016)] reported the instability induced by pressure ionization in fluid helium based on minimization of Helmholtz free energy within chemical picture. Here, I argue that their calculations may have some bugs directly resulting in the so-called instability, because a problematic iterative strategy also produces a similar, but mathematically incorrect instability that can be removed by improving iterative strategy.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. The JAK/STAT signaling cascade in gastric carcinoma (Review).

    PubMed

    Khanna, Puja; Chua, Pei Jou; Bay, Boon Huat; Baeg, Gyeong Hun

    2015-11-01

    Gastric carcinoma remains one of the most prevalent forms of cancer worldwide, despite the decline in incidence rates, increased awareness of the disease and advancement in treatment strategies. Helicobacter pylori infection, dietary factors, lifestyle influences and various genetic aberrations have been shown to contribute to the development and progression of gastric cancer. Recent studies on the genomic landscape of gastric adenocarcinoma have identified several key signaling molecules, including epidermal growth factor receptor family (ErbB) members, vascular endothelial growth factor receptor family (VEGFR) members and PI3K/Akt/mTOR pathway components, that have been implicated in the molecular pathogenesis of gastric cancers. However, clinical trials with compounds that target these molecules have failed to show a significant improvement in overall survival rates when supplemented with conventional therapies. Therefore, it is essential to identify effective prognostic and/or diagnostic biomarkers and develop molecular targeted therapies. The JAK/STAT cascade is a principal signal transduction pathway in cytokine and growth factor signaling, regulating various cellular processes such as cell proliferation, differentiation, migration and survival. Numerous in vivo and in vitro studies have shown that dysregulated JAK/STAT signaling is a driving force in the pathogenesis of various solid cancers as well as hematopoietic malignancies. Hence, a large number of preclinical and clinical studies of drugs targeting this pathway are currently underway. Notably, aberrant JAK/STAT signaling has also been implicated in gastric cancers. In this review, we focus on the ongoing research on the JAK/STAT cascade in gastric carcinoma and discuss the therapeutic potential of targeting JAK/STAT signaling for the treatment of gastric cancer.

  7. 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.

  8. Akt is required for Stat5 activation and mammary differentiation

    PubMed Central

    2010-01-01

    Introduction The Akt pathway plays a central role in regulating cell survival, proliferation and metabolism, and is one of the most commonly activated pathways in human cancer. A role for Akt in epithelial differentiation, however, has not been established. We previously reported that mice lacking Akt1, but not Akt2, exhibit a pronounced metabolic defect during late pregnancy and lactation that results from a failure to upregulate Glut1 as well as several lipid synthetic enzymes. Despite this metabolic defect, however, both Akt1-deficient and Akt2-deficient mice exhibit normal mammary epithelial differentiation and Stat5 activation. Methods In light of the overlapping functions of Akt family members, we considered the possibility that Akt may play an essential role in regulating mammary epithelial development that is not evident in Akt1-deficient mice due to compensation by other Akt isoforms. To address this possibility, we interbred mice bearing targeted deletions in Akt1 and Akt2 and determined the effect on mammary differentiation during pregnancy and lactation. Results Deletion of one allele of Akt2 in Akt1-deficient mice resulted in a severe defect in Stat5 activation during late pregnancy that was accompanied by a global failure of terminal mammary epithelial cell differentiation, as manifested by the near-complete loss in production of the three principal components of milk: lactose, lipid, and milk proteins. This defect was due, in part, to a failure of pregnant Akt1-/-;Akt2+/- mice to upregulate the positive regulator of Prlr-Jak-Stat5 signaling, Id2, or to downregulate the negative regulators of Prlr-Jak-Stat5 signaling, caveolin-1 and Socs2. Conclusions Our findings demonstrate an unexpected requirement for Akt in Prlr-Jak-Stat5 signaling and establish Akt as an essential central regulator of mammary epithelial differentiation and lactation. PMID:20849614

  9. 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

  10. 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.

  11. 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.

  12. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25881542

  14. 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.

  15. '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.

  16. Differential activation of acute phase response factor/Stat3 and Stat1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130. II. Src homology SH2 domains define the specificity of stat factor activation.

    PubMed

    Hemmann, U; Gerhartz, C; Heesel, B; Sasse, J; Kurapkat, G; Grötzinger, J; Wollmer, A; Zhong, Z; Darnell, J E; Graeve, L; Heinrich, P C; Horn, F

    1996-05-31

    Distinct yet overlapping sets of STAT transcription factors are activated by different cytokines. One example is the differential activation of acute phase response factor (APRF, also called Stat3) and Stat1 by interleukin 6 and interferon-gamma. Interleukin 6 activates both factors while, at least in human cells, interferon-gamma recruits only Stat1. Stat1 activation by interferon-gamma is mediated through a cytosolic tyrosine motif, Y440, of the interferon-gamma receptor. In an accompanying paper (Gerhartz, C., Heesel, B., Sasse, J., Hemmann, U., Landgraf, C., Schneider-Mergener, J., Horn, F., Heinrich, P. C., and Graeve, L. (1996) J. Biol. Chem. 271, 12991-12998), we demonstrated that two tyrosine motifs within the cytoplasmic part of the interleukin 6 signal transducer gp130 specifically mediate APRF activation while two others can recruit both APRF and Stat1. By expressing a series of Stat1/APRF domain swap mutants in COS-7 cells, we now determined which domains of Stat1 and APRF are involved in the specific recognition of phosphotyrosine motifs. Our data demonstrate that the SH2 domain is the sole determinant of specific STAT factor recruitment. Furthermore, the SH2 domain of Stat1 is able to recognize two unrelated types of phosphotyrosine motifs, one represented by the interferon-gamma receptor Y440DKPH peptide, and the other by two gp130 YXPQ motifs. By molecular modeling, we propose three-dimensional model structures of the Stat1 and APRF SH2 domains which allow us to explain the different binding preferences of these factors and to predict amino acids crucial for specific peptide recognition.

  17. Characterization of phosphopeptide motifs specific for the Src homology 2 domains of signal transducer and activator of transcription 1 (STAT1) and STAT3.

    PubMed

    Wiederkehr-Adam, Michèle; Ernst, Philipp; Müller, Kurt; Bieck, Elke; Gombert, Frank O; Ottl, Johannes; Graff, Patrick; Grossmüller, Fred; Heim, Markus H

    2003-05-02

    Signal transducers and activators of transcription (STAT) 1 and STAT3 are activated by overlapping but distinct sets of cytokines. STATs are recruited to the different cytokine receptors through their Src homology (SH) 2 domains that make highly specific interactions with phosphotyrosine-docking sites on the receptors. We used a degenerate phosphopeptide library synthesized on 35-microm TentaGel beads and fluorescence-activated bead sorting to determine the sequence specificity of the peptide-binding sites of the SH2 domains of STAT1 and STAT3. The large bead library allowed not only peptide sequencing of pools of beads but also of single beads. The method was validated through surface plasmon resonance measurements of the affinities of different peptides to the STAT SH2 domains. Furthermore, when selected peptides were attached to a truncated erythropoietin receptor and stably expressed in DA3 cells, activation of STAT1 or STAT3 could be achieved by stimulation with erythropoietin. The combined analysis of pool sequencing, the individual peptide sequences, and plasmon resonance measurements allowed the definition of SH2 domain binding motifs. STAT1 preferentially binds peptides with the motif phosphotyrosine-(aspartic acid/glutamic acid)-(proline/arginine)-(arginine/proline/glutamine), whereby a negatively charged amino acid at +1 excludes a proline at +2 and vice versa. STAT3 preferentially binds peptides with the motif phosphotyrosine-(basic or hydrophobic)-(proline or basic)-glutamine. For both STAT1 and STAT3, specific high affinity phosphopeptides were identified that can be used for the design of inhibitory molecules.

  18. IL-27 induces Th17 differentiation in the absence of STAT1 signaling1

    PubMed Central

    Peters, Anneli; Fowler, Kevin D.; Chalmin, Fanny; Merkler, Doron; Kuchroo, Vijay K.; Pot, Caroline

    2015-01-01

    It is known that differentiation of Th17 cells is promoted by activation of STAT3 and inhibited by activation of STAT1. Although both transcription factors are activated by several cytokines including IL-6, IL-21 and IL-27, each of these cytokines has very different effects on Th17 differentiation ranging from strong induction (IL-6) to strong inhibition (IL-27). To determine the molecular basis for these differences, we measured STAT3 and STAT1 activation profiles for IL-6, IL-21, and IL-27, as well as for cytokine pairs over time. We found that the ratio of activated STAT3 to activated STAT1, is crucial in determining whether cytokines promote or inhibit Th17 differentiation. Thus, IL-6 and IL-21 induced pSTAT3:pSTAT1 ratios greater than one leading to promotion of Th17 differentiation, whereas IL-27 or IL-6+IL27 induced pSTAT3:pSTAT1 ratios below one resulting in inhibition of Th17 differentiation. Consistent with these findings, we show that IL-27 induces sufficient pSTAT3 to promote Th17 differentiation in the absence of STAT1. Furthermore, IL-27-induced STAT1-deficient T cells were indistinguishable from bona fide highly pro-inflammatory Th17 cells, as they induced severe experimental autoimmune encephalomyelitis (EAE) upon adoptive transfer. Our results suggest, that the ratio of pSTAT3:pSTAT1 induced by a cytokine or cytokine pairs can be used to predict whether or not they induce a competent Th17 differentiation program. PMID:26408664

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. Wick materials by sol-gel processing

    SciTech Connect

    Nazeri, Azar; Kim, Jeong

    1997-01-10

    In capillary pumped loops (CPL) devices, the fine porous wick, located in the evaporator, provides the means for passively pumping the fluid through the system, using surface tension forces exerted onto a liquid in a small diameter pore at the liquid/vapor interface. The Naval Research Laboratory's Materials Science and technology Division and Naval Center for Space Technology have been investigating the use of sol-gel processing for development of organically modified ceramic wicks with micron or submicron pores, high porosity, low thermal conductivity and structural flexibility. Gels with average pore sizes as small as 0.5 {mu}m, 30-80% continuous porosity, some flexibility and thermal stability to at least 473K were successfully prepared. Microstructures of these hybrids were examined by scanning electron microscopy (SEM), and some conventional wick property testing were performed.

  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. Opportunity's View of 'Viking' Crater, Sol 421

    NASA Technical Reports Server (NTRS)

    2005-01-01

    On the 421st martian day, or sol, of its time on Mars (March 31,2005), NASA's Mars Exploration Rover Opportunity drove to within about 10 meters (33 feet) of a small crater called 'Viking.' After completing the day's 71-meter (233-foot) drive across flatland of the Meridiani Planum region, the rover used its navigation camera to take images combined into this view of its new surroundings, including the crater. That day was the last of Opportunity's second extended mission. On April 1, both Opportunity and its twin, Spirit, began third extensions approved by NASA for up to 18 more months of exploring Mars. This view is presented in a cylindrical projection with geometric seam correction.

  9. Rover Panorama from Sols 75 & 76

    NASA Technical Reports Server (NTRS)

    1998-01-01

    This Sojourner rover panorama from Sols 75 and 76 is the only true panorama product (as opposed to the normal 'tiled' full frames) produced by the rover. This panorama ranges from Big Crater on the left (about azimuth 160 degrees), past the Twin Peaks and almost all the way to the north horizon, for a swath of about 200 degrees in azimuth.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California Institute of Technology (Caltech).

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. Targeting transcription factor Stat5a/b as a therapeutic strategy for prostate cancer

    PubMed Central

    Liao, Zhiyong; Nevalainen, Marja T

    2011-01-01

    Signal transducer and activator of transcription 5 (Stat5) is critical for the viability and growth of human prostate cancer cells in culture and for prostate xenograft tumors in nude mice. The expression of nuclear active Stat5a/b is associated with high histological grades of clinical prostate cancers, and the presence of active Stat5a/b in prostate cancer predicts early disease recurrence. Stat5a/b and androgen receptor signaling pathways functionally synergize in prostate cancer cells, and recent work suggests that Stat5a/b may be involved in the progression of prostate cancer to metastatic disease. Here, we review the biological functions of Stat5a/b in prostate cancer and potential strategies to target the prolactin receptor (PrlR)/Jak2/Stat5 signaling pathway for therapy development for prostate cancer. PMID:21416055

  19. 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.

  20. 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.