A 40 kDa inhibitor of protein kinase C purified from bovine brain

AbstractAn inhibitor of protein kinase C has been purified to homogeneity from bovine brain cytosol by a four-step method. It is heat stable, has an apparent molecular mass of 40 kDa and is composed of two polypeptide chains of 19 kDa

Trapezoidal sheeting made of stainless steel two amendments to the design codes

Trapezoidal sheeting made of stainless steel can be used for applications with high requirements on visual appearance or corrosion resistance. The calculation of the load-bearing capacity of thin-walled structures including trapezoidal sheeting normally follows the procedures of EN 1993-1-3 and similar codes. EN 1993-1-4 complements this standard concerning thin-walled structures made of stainless steel. This standard relies on many publications on thin-walled structures made of stainless steel. But unfortunately these publications almost all focus on thin-walled beams and columns and therefore some topics that are specific to trapezoidal sheeting are not recognized. The results of the presented research results on the load-bearing behaviour of thin-walled trapezoidal sheeting made of stainless steel are closing this gap: With the proposed additions to the existing design formulae, the complete calculation of the load-bearing capacity of trapezoidal sheeting made of stainless steel is possible

Synthesis and properties of perfluoroalkyl groups containing double four-ring spherosilicate (siloxysilsesquioxane) precursors

Organically modified cage-like double four-ring spherosilicates have received considerable interest in the construction of nanosized hybrid materials, as well as building units for structural well-defined polymers. This group is extended by perfluoroalkyl ligands containing spherosilicates, synthesized by addition reaction of the octahydridodimethlysiloxyoctasilsesquioxane [H(CH3)2Si]8Si8O20 and heptadecafluorodecyl methacrylate. The resultant liquid spherosilicate substituted with eight terminal perfluoroalkyl groups was characterized by 29 and 13C NMR spectroscopies and MALDI Time-of-Flight mass spectrometry. Partial substitution of perfluoroalkyl ligands by trimethoxysilyl containing groups provides condensable precursors for the synthesis of hydrophobic and oleophobic materials via the sol-gel process. This new spherosilicate, carrying on average four perfluoroalkyl groups and four trimethoxysilyl groups shows better hydrophobic and oleophobic properties compared with commonly used perfluoroalkyltrialkoxysilanes under identical concentration of perfluoroalkyl chains. In addition a comprehensive literature survey is given on structural well characterized, organically modified cage-like double four-ring spherosilicates

Intrathecal heat shock protein 60 mediates neurodegeneration and demyelination in the CNS through a TLR4- and MyD88-dependent pathway

Background Toll-like receptors (TLR) constitute a highly conserved class of receptors through which the innate immune system responds to both pathogen- and host-derived factors. Although TLRs are involved in a wide range of central nervous system (CNS) disorders including neurodegenerative diseases, the molecular events leading from CNS injury to activation of these innate immune receptors remain elusive. The stress protein heat shock protein 60 (HSP60) released from injured cells is considered an endogenous danger signal of the immune system. In this context, the main objective of the present study was to investigate the impact of extracellular HSP60 on the brain in vivo. Results We show here that HSP60 injected intrathecally causes neuronal and oligodendrocyte injury in the CNS in vivo through TLR4-dependent signaling. Intrathecal HSP60 results in neuronal cell death, axonal injury, loss of oligodendrocytes, and demyelination in the cerebral cortex of wild-type mice. In contrast both mice lacking TLR4 and the TLR adaptor molecule MyD88 are protected against deleterious effects induced by HSP60. In contrast to the exogenous TLR4 ligand, lipopolysaccharide, intrathecal HSP60 does not induce such a considerable inflammatory response in the brain. In the CNS, endogenous HSP60 is predominantly expressed in neurons and released during brain injury, since the cerebrospinal fluid (CSF) from animals of a mouse stroke model contains elevated levels of this stress protein compared to the CSF of sham- operated mice. Conclusions Our data show a direct toxic effect of HSP60 towards neurons and oligodendrocytes in the CNS. The fact that these harmful effects involve TLR4 and MyD88 confirms a molecular pathway mediated by the release of endogenous TLR ligands from injured CNS cells common to many forms of brain diseases that bi-directionally links CNS injury and activation of the innate immune system to neurodegeneration and demyelination in vivo

Overview: On the transport and transformation of pollutants in the outflow of major population centres – observational data from the EMeRGe European intensive operational period in summer 2017

Megacities and other major population centres (MPCs) worldwide are major sources of air pollution, both locally as well as downwind. The overall assessment and prediction of the impact of MPC pollution on tropospheric chemistry are challenging. The present work provides an overview of the highlights of a major new contribution to the understanding of this issue based on the data and analysis of the EMeRGe (Effect of Megacities on the transport and transformation of pollutants on the Regional to Global scales) international project. EMeRGe focuses on atmospheric chemistry, dynamics, and transport of local and regional pollution originating in MPCs. Airborne measurements, taking advantage of the long range capabilities of the High Altitude and LOng Range Research Aircraft (HALO, https://www.halo-spp.de, last access: 22 March 2022), are a central part of the project. The synergistic use and consistent interpretation of observational data sets of different spatial and temporal resolution (e.g. from ground-based networks, airborne campaigns, and satellite measurements) supported by modelling within EMeRGe provide unique insight to test the current understanding of MPC pollution outflows. In order to obtain an adequate set of measurements at different spatial scales, two field experiments were positioned in time and space to contrast situations when the photochemical transformation of plumes emerging from MPCs is large. These experiments were conducted in summer 2017 over Europe and in the inter-monsoon period over Asia in spring 2018. The intensive observational periods (IOPs) involved HALO airborne measurements of ozone and its precursors, volatile organic compounds, aerosol particles, and related species as well as coordinated ground-based ancillary observations at different sites. Perfluorocarbon (PFC) tracer releases and model forecasts supported the flight planning, the identification of pollution plumes, and the analysis of chemical transformations during transport. This paper describes the experimental deployment and scientific questions of the IOP in Europe. The MPC targets – London (United Kingdom; UK), the Benelux/Ruhr area (Belgium, the Netherlands, Luxembourg and Germany), Paris (France), Rome and the Po Valley (Italy), and Madrid and Barcelona (Spain) – were investigated during seven HALO research flights with an aircraft base in Germany for a total of 53 flight hours. An in-flight comparison of HALO with the collaborating UK-airborne platform Facility for Airborne Atmospheric Measurements (FAAM) took place to assure accuracy and comparability of the instrumentation on board. Overall, EMeRGe unites measurements of near- and far-field emissions and hence deals with complex air masses of local and distant sources. Regional transport of several European MPC outflows was successfully identified and measured. Chemical processing of the MPC emissions was inferred from airborne observations of primary and secondary pollutants and the ratios between species having different chemical lifetimes. Photochemical processing of aerosol and secondary formation or organic acids was evident during the transport of MPC plumes. Urban plumes mix efficiently with natural sources as mineral dust and with biomass burning emissions from vegetation and forest fires. This confirms the importance of wildland fire emissions in Europe and indicates an important but discontinuous contribution to the European emission budget that might be of relevance in the design of efficient mitigation strategies. The present work provides an overview of the most salient results in the European context, with these being addressed in more detail within additional dedicated EMeRGe studies. The deployment and results obtained in Asia will be the subject of separate publications.The HALO deployment during EMeRGe was funded by a consortium comprising the German Research Foundation (DFG) Priority Program HALO-SPP 1294, the Institute of Atmospheric Physics of DLR, the Max Planck Society (MPG), and the Helmholtz Association. Flora Kluge, Benjamin Schreiner, and Klaus Pfeilsticker acknowledge the support given by the DFG through the project nos. PF 384-16, PF 384-17, and PG 385-19. Ralf Koppmann and Marc Krebsbach acknowledge DFG funding through project no. KR3861_1-1. Katja Bigge acknowledges additional funding from the Heidelberg Graduate School for Physics. Johannes Schneider, Katharina Kaiser, and Stephan Borrmann acknowledge funding through the DFG (project no. 316589531). Lisa Eirenschmalz and Hans Schlager acknowledge support by DFG through project MEPOLL (SCHL1857/4-1). Anna B. Kalisz Hedegaard would like to thank DAAD and DLR for a Research Fellowship. Hans Schlager acknowledge financial support by the DLR TraK (Transport and Climate) project. Michael Sicard acknowledges support from the EU (GA nos. 654109, 778349, 871115, and 101008004) and the Spanish Government (ref. nos. CGL2017-90884-REDT, PID2019-103886RB-I00, RTI2018-096548-B-I00, and MDM-2016-0600). Midhun George, Yangzhuoran Liu, M. Dolores Andrés Hernández, and John Phillip Burrows acknowledge financial support from the University of Bremen. FLEXPART simulations were performed on the HPC cluster Aether at the University of Bremen, financed by DFG within the scope of the Excellence Initiative. Anne-Marlene Blechschmidt was partly funded through the CAMS-84 project. Jennifer Wolf acknowledges support from the German Federal Ministry for Economic Affairs and Energy – BMWi (project Digitally optimized Engineering for Services – DoEfS; contract no. 20X1701B). Theresa Harlass thanks DLR VOR for funding the young investigator research group “Greenhouse Gases”. Mariano Mertens, Patrick Jöckel, and Markus Kilian acknowledge resources of the Deutsches Klimarechenzentrum (DKRZ) granted by the WLA project ID bd0617 for the MECO(n) simulations and the financial support from the DLR projects TraK (Transport und Klima) and the Initiative and Networking Fund of the Helmholtz Association through the project “Advanced Earth System Modelling Capacity” (ESM). Bruna A. Holanda acknowledges the funding from Brazilian CNPq (process 200723/2015-4).Peer ReviewedArticle signat per 53 autors/es: M. Dolores Andrés Hernández (1), Andreas Hilboll (2), Helmut Ziereis (3), Eric Förster (4), Ovid O. Krüger (5), Katharina Kaiser (6,7), Johannes Schneider (7), Francesca Barnaba (8), Mihalis Vrekoussis (2,18), Jörg Schmidt (9), Heidi Huntrieser (3), Anne-Marlene Blechschmidt (1), Midhun George (1), Vladyslav Nenakhov (1,a), Theresa Harlass (3), Bruna A. Holanda (5), Jennifer Wolf (3), Lisa Eirenschmalz (3), Marc Krebsbach (10), Mira L. Pöhlker (5,b), Anna B. Kalisz Hedegaard (3,2), Linlu Mei (1), Klaus Pfeilsticker (11), Yangzhuoran Liu (1), Ralf Koppmann (10), Hans Schlager (3), Birger Bohn (12), Ulrich Schumann (3), Andreas Richter (1), Benjamin Schreiner (11), Daniel Sauer (3), Robert Baumann (3), Mariano Mertens (3), Patrick Jöckel (3), Markus Kilian (3), Greta Stratmann (3,c,) Christopher Pöhlker (5), Monica Campanelli (8), Marco Pandolfi (13), Michael Sicard (14,15), José L. Gómez-Amo (16), Manuel Pujadas (17), Katja Bigge (11), Flora Kluge (11), Anja Schwarz (9), Nikos Daskalakis (2), David Walter (5), Andreas Zahn (4), Ulrich Pöschl (5), Harald Bönisch (4), Stephan Borrmann (6,7), Ulrich Platt (11), and John P. Burrows (1) // (1) Institute of Environmental Physics, University of Bremen, Bremen, Germany; (2) Laboratory for Modeling and Observation of the Earth System, Institute of Environmental Physics, Bremen, Germany; (3) Deutsches Zentrum für Luft- und Raumfahrt (DLR), Institut für Physik der Atmosphäre, Oberpfaffenhofen, Germany; (4) Atmospheric Trace Gases and Remote Sensing, Karlsruhe Institute of Technology, Institute of Meteorology and Climate Research, Karlsruhe, Germany; (5) Multiphase Chemistry Department, Max Planck Institute for Chemistry, Mainz, Germany; (6) Institute for Atmospheric Physics, Johannes Gutenberg University, Mainz, Germany, (7) Particle Chemistry Department, Max Planck Institute for Chemistry, Mainz, Germany; (8) National Research Council of Italy, Institute of Atmospheric Sciences and Climate (CNR-ISAC), Rome, Italy; (9) Leipzig Institute for Meteorology, Leipzig University, Leipzig, Germany; (10) Institute for Atmospheric and Environmental Research, University of Wuppertal, Wuppertal, Germany; (11) Institute for Environmental Physics, University of Heidelberg, Heidelberg, Germany, (12) Institute of Energy and Climate Research IEK-8, Forschungszentrum Jülich, Jülich, Germany; (13) Consejo Superior de Investigaciones Científicas, Institute of Environmental Assessment and Water Research, Barcelona, Spain; (14) CommSensLab, Department of Signal Theory and Communications, Universitat Politècnica de Catalunya, Barcelona, Spain; (15) Ciències i Tecnologies de l’Espai-Centre de Recerca de l’Aeronàutica i de l’Espai/Institut d’Estudis Espacials de Catalunya), Universitat Politècnica de Catalunya, Barcelona, Spain; (16) Department of Earth Physics and Thermodynamics, University of Valencia, Burjassot, Spain; (17) Atmospheric Pollution Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (Ciemat), Madrid, Spain; (18) Climate and Atmosphere Research Center (CARE-C), The Cyprus Institute, Nicosia, Cyprus anow at: Flight Experiments, Deutsches Zentrum für Luft- und Raumfahrt (DLR), Oberpfaffenhofen, GermanyPostprint (published version

Применение технологий клиентоориентированного маркетинга для поддержания и развития имиджа компании

Актуальность проблем, освещенных в данной работе, заключается в необходимости изучения потребителя, при условии постоянного изменения поведения клиентов компании ввиду высокой конкуренции на розничном рынке электроники. Проблема. С помощью каких нововведений можно повысить клиентоориентированность компании ООО «М.видео Менеджмент» и её имидж? Объектом исследования ВКР являются маркетинговые коммуникации ООО «М.видео Менеджмент». Предмет исследования – технологии коммуникационных стратегий организации. Цель работы – разработка программы лояльности для поддержания и развития имиджа компании (на примере ООО «М.видео Менеджмент» г. Томск). Методологической основой исследования являются абстрактно- логические, экономико-статистические методы, а также использование системного подхода, применение методов сравнения, группировок, графического отображения исследуемой информации. Практическая значимость исследования заключается в том, что предложенная и разработанная программа лояльности может быть использована в других компаниях для поддержки и развития имиджа компании.The relevance of the issues discussed in this paper is to study the consumer, the subject of constant change of customer behavior due to high competition in the retail market of electronics. Problem. What innovations can enhance the customer focus of the company "M. video Management" and its image? The object of research WRC is the marketing communications LLC "M. video Management". Subject of research – technology communication strategies of the organization. The work purpose – development of loyalty programs for the maintenance and development of the company's image (on the example of OOO "M. video Management" Tomsk). The methodological basis of the research is abstract - logic, economic-statistical methods, and the use of a systematic approach, applying the methods of comparison of groups graphical display of researched information. Practical significance of the research lies in the fact that the proposed and developed loyalty program can be used in other companies for the support and development of the company's image

The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia

<p>Abstract</p> <p>Background</p> <p>The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD), RNA amplification, and array hybridization.</p> <p>Results</p> <p>Profiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA) displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types.</p> <p>Conclusion</p> <p>The differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected influence of a strong noxious stimulus on cell-specific gene expression differences can be explained by the activation of a cell-type independent conserved gene-expression program. Our data generate both novel insights into the relation of the quiescent and stimulus-induced transcriptome in different cells, and provide a large dataset to the research community, both for mapping purposes, as well as for physiological and pathophysiological research.</p

Effects of transport on a biomass burning plume from Indochina during EMeRGe-Asia identified by WRF-Chem

The Indochina biomass burning (BB) season in springtime has a substantial environmental impact on the surrounding areas in Asia. In this study, we evaluated the environmental impact of a major long-range BB transport event on 19 March 2018 (a flight of the High Altitude and Long Range Research Aircraft (HALO; https://www.halo-spp.de, last access: 14 February 2023) research aircraft, flight F0319) preceded by a minor event on 17 March 2018 (flight F0317). Aircraft data obtained during the campaign in Asia of the Effect of Megacities on the transport and transformation of pollutants on the Regional to Global scales (EMeRGe) were available between 12 March and 7 April 2018. In F0319, results of 1 min mean carbon monoxide (CO), ozone (O$_3$), acetone (ACE), acetonitrile (ACN), organic aerosol (OA), and black carbon aerosol (BC) concentrations were up to 312.0, 79.0, 3.0, and 0.6 ppb and 6.4 and 2.5 µg m$^{−3}$, respectively, during the flight, which passed through the BB plume transport layer (BPTL) between the elevation of 2000–4000 m over the East China Sea (ECS). During F0319, the CO, O$_3$, ACE, ACN, OA, and BC maximum of the 1 min average concentrations were higher in the BPTL by 109.0, 8.0, 1.0, and 0.3 ppb and 3.0 and 1.3 µg m$^{−3}$ compared to flight F0317, respectively. Sulfate aerosol, rather than OA, showed the highest concentration at low altitudes (<1000 m) in both flights F0317 and F0319 resulting from the continental outflow in the ECS. The transport of BB aerosols from Indochina and its impacts on the downstream area were evaluated using a Weather Research Forecasting with Chemistry (WRF-Chem) model. The modeling results tended to overestimate the concentration of the species, with examples being CO (64 ppb), OA (0.3 µg m$^{−3}$), BC (0.2 µg m$^{−3}$), and O$_3$ (12.5 ppb) in the BPTL. Over the ECS, the simulated BB contribution demonstrated an increasing trend from the lowest values on 17 March 2018 to the highest values on 18 and 19 March 2018 for CO, fine particulate matter (PM$_{2.5}$), OA, BC, hydroxyl radicals (OH), nitrogen oxides (NO$_x$), total reactive nitrogen (NO$_y$), and O$_3$; by contrast, the variation of J(O$^1$D) decreased as the BB plume\u27s contribution increased over the ECS. In the lower boundary layer (<1000 m), the BB plume\u27s contribution to most species in the remote downstream areas was <20 %. However, at the BPTL, the contribution of the long-range transported BB plume was as high as 30 %–80 % for most of the species (NO$_y$, NO$_x$, PM$_{2.5}$, BC, OH, O$_3$, and CO) over southern China (SC), Taiwan, and the ECS. BB aerosols were identified as a potential source of cloud condensation nuclei, and the simulation results indicated that the transported BB plume had an effect on cloud water formation over SC and the ECS on 19 March 2018. The combination of BB aerosol enhancement with cloud water resulted in a reduction of incoming shortwave radiation at the surface in SC and the ECS by 5 %–7 % and 2 %–4 %, respectively, which potentially has significant regional climate implications

Megapixels @ Megahertz -- The AGIPD High-Speed Cameras for the European XFEL

The European XFEL is an extremely brilliant Free Electron Laser Source with a very demanding pulse structure: trains of 2700 X-Ray pulses are repeated at 10 Hz. The pulses inside the train are spaced by 220 ns and each one contains up to $10^{12}$ photons of 12.4 keV, while being $\le 100$ fs in length. AGIPD, the Adaptive Gain Integrating Pixel Detector, is a hybrid pixel detector developed by DESY, PSI, and the Universities of Bonn and Hamburg to cope with these properties. It is a fast, low noise integrating detector, with single photon sensitivity (for $\text{E}_{\gamma} \ge 6$ keV) and a large dynamic range, up to $10^4$ photons at 12.4 keV. This is achieved with a charge sensitive amplifier with 3 adaptively selected gains per pixel. 352 images can be recorded at up to 6.5 MHz and stored in the in-pixel analogue memory and read out between pulse trains. The core component of this detector is the AGIPD ASIC, which consists of $64 \times 64$ pixels of $200 {\mu}\text{m} \times 200 {\mu}\text{m}$. Control of the ASIC's image acquisition and analogue readout is via a command based interface. FPGA based electronic boards, controlling ASIC operation, image digitisation and 10 GE data transmission interface AGIPD detectors to DAQ and control systems. An AGIPD 1 Mpixel detector has been installed at the SPB experimental station in August 2017, while a second one is currently commissioned for the MID endstation. A larger (4 Mpixel) AGIPD detector and one to employ Hi-Z sensor material to efficiently register photons up to $\text{E}_{\gamma} \approx 25$ keV are currently under construction.Comment: submitted to the proceedings of the ULITIMA 2018 conference, to be published in NIM