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Therapy-Induced Changes of Gene Expression in a Matched Pair of Small Cell Lung Cancer (SCLC) Cell Lines

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Journal of Cancer Therapy 2012年第4期3卷 442-451页

作者： Gerhard Hamilton ernst ulsperger Klaus Geissler Ulrike Olszewski Ludwig Boltzmann Cluster of Translational Oncology Vienna Austria

Extended stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses early as drug-resistant tumor associated with a dismal prognosis. A pair of SCLC cell lines obtained from a single patient at different time points during treatment allows for the investigation of the changes in gene expression prior to (GLC14) and following cycles of chemotherapy and irradiation (GLC19). GLC19 cells were reported to reveal an increased doubling time and exhibit increased chemoresistance to doxorubicin, etoposide, melphalan and vinblastine. Upregulated transcripts in GLC19, as assessed by microarray analysis, comprised proteins involved in regulation of cellular growth (NGFRAP1/BEX3), adhesion, glutathione metabolism and, in particular, WNT/Notch pathways and the putative cancer stem cell phenotype (CD44, ALDH1A1, and AKR1C1/13). Metallothioneins, tubulins TUBA3/4 and tumor protein p53 inducible protein 11 (TP53IP11) were downregulated in this cell line compared to GLC14. Except increased expression of glutathione transferases no classical markers of chemoresistance were found, pointing to a role of altered growth control/differentiation and reduced accessibility of this SCLC tumor cells growing as multicellular spheroids. In conclusion, treatment of this single SCLC with cyclophosphamide, doxorubicin and etoposide (CDE) followed by radiotherapy ultimately resulted in an enrichment of tumor cells displaying the typical signature of tumor-initiating or cancer stem cells (CIC/CSC).

关键词： Small Cell Lung Cancer GLC14 GLC19 Chemotherapy Chemoresistance Gene Expression Cancer-Initiating Cells

Synergistic Anticancer Activity of Topotecan— Cyclin-Dependent Kinase Inhibitor Combinations against Drug-Resistant Small Cell Lung Cancer (SCLC) Cell Lines

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Journal of Cancer Therapy 2013年第8期4卷 47-53页

作者： Gerhard Hamilton Ulrike Olszewski, Lukas Klameth ernst ulsperger Klaus Geissler Ludwig Boltzmann Cluster of Translational Oncology Vienna Austria Ludwig Boltzmann Cluster of Translational Oncology Vienna Austria.

Extended-stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses rapidly as drug-resistant tumor. Topotecan (TPT) is the single chemotherapeutic agent approved for second-line treatment of SCLC. However, the response to TPT is short-lived and novel treatment modalities need to be developed. Sequential treatment of cytotoxic drugs and inhibitors of cyclin-dependent kinases (CDKs) showed promising preclinical anticancer activity and, in the present work, combinations of TPT with CDK inhibitors olomoucine, roscovitine and CDK4I are shown to exhibit synergistic cytotoxic activity against SCLC cell lines. Highest activity was found against TPT-resistant NCI-H417 and DMS153 cell lines and moderate chemosensitizing effects against a primary SCLC cell line and sensitive GLC19 cells at levels of CDK inhibitors which exerted low toxicity. A combination of 0.6 μM TPT with 0.6 μM roscovitine, exhibiting no significant cytotoxicity as single agents, reduced viability of the TPT-resistant NCI-H417 line (IC50 > 10 μM) by 50%. In the TPT resistant cell lines olomoucine and roscovitine, targeting CDK1,2,5,7, were highly effective, whereas in the more sensitive cell lines CDK4I, inhibiting mainly CDK4/6, showed activity. In NCI-417 cells, preincubation with roscovitine for one day proved synergistic with TPT. Thus, in good accordance with previous findings, CDK inhibitors are able to convert SCLC cancer cells which are cell-cycle arrested by a blockade of topoisomerase I by TPT to apoptotic cells. Since nowadays several CDK inhibitors are at various phases of clinical testing their combination with TPT seems to constitute a promising approach to improve second-line chemotherapy in SCLC.

关键词： Small Cell Lung Cancer Chemoresistance Topotecan CDK Inhibitor Olomoucine Roscovitine

CONJUGATE-SYMPLECTICITY OF LINEAR MULTISTEP METHODS

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Journal of Computational Mathematics 2008年第5期26卷 657-659页

作者： ernst Hairer Section de Mathématiques Univ.de Genève

For the numerical treatment of Hamiltonian differential equations, symplectic integrators are the most suitable choice, and methods that are conjugate to a symplectic integrator share the same good long-time behavior. This note characterizes linear multistep methods whose underlying one-step method is conjugate to a symplectic integrator. The bounded- hess of parasitic solution components is not addressed.

关键词： Linear multistep method Underlying one-step method Conjugate-symplecticity,Symmetry.

Insensitive high explosives:Ⅳ. Nitroguanidine-Initiation & detonation

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Defence Technology（防务技术） 2019年第4期15卷 467-487页

作者： ernst-Christian Koch Lutradyn-Energetic Materials

This paper reviews the detonative properties of low bulk density(LBD),high bulk density(HBD)Nitroguanidine(NGu)(1),CAS-No:[556-88-7]and 82 explosive formulations based on NGu reported in the public *** rank the performance of those formulations they are compared with 15 reference compositions containing both standard high explosives such as octogen(HMX)(2),hexogen(RDX)(3),pentaerythritol tetranitrate(PETN)(4),2,4,6-trinitrotoluene(TNT)(5)as well as insensitive high explosives such as 3-nitro-1,2,4-triazolone(NTO)(6),1,3,5-triamino-2,4,6-trinitrobenzene(TATB)(7),1,1-diamino-2,2-dinitroethylene(FOX-7)(8)and N-Guanylurea dinitramide(FOX 12)(9).NGu based formulations are superior to those based on FOX-12 or TATB and are a close match with FOX-7 based explosives,the latter just having higher Gurney Energies(-10%)and slightly higher detonation pressure(+2%).NGu based explosives even reach up to 78% of the detonation pressure,82% Gurney energy and up to 95% of detonation velocity of ***-NGu dissolves in many melt cast eutectics forming dense charges thereby eliminating the need for costly High Bulk Density *** based formulations are at the rock bottom of sensitiveness among all the above-mentioned explosives which contributes to the safety of these *** review gives 132 references to the public *** a review on the synthesis spectroscopy and sensitiveness of Nitroguanidine see Ref.[1].

关键词： Cook-off Detonation Insensitive munitions Nitroguanidine Shock sensitvity

Special materials in pyrotechnics Ⅶ: Pyrotechnics used in thermal batteries

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Defence Technology（防务技术） 2019年第3期15卷 254-263页

作者： ernst-Christian Koch Lutradyn Energetic Materials Science & Technology

Thermal batteries are unique direct current(DC) electrical power sources with long shelf live, high reliability and higher power density than classical alkaline batteries. This paper gives a brief overview into the working principle of thermal batteries and reviews the properties of zirconium/barium chromate(Zr/BaCrO4) pyrolant previously used as first fire and iron/potassium perchlorate(Fe/KClO4) pyrolant(Heat), commonly applied as heating pellet in thermal batteries and its hazard properties. The review gives 64 references to the public domain. CAS-Nos. Zr: [7440-67-7], BaCrO4: [10294-40-3], Fe: [7439-89-6], KClO4: [7778-74-7], Viton: [9011-17-0].CAS-Nos. Zr: [7440-67-7], BaCrO4: [10294-40-3], Fe: [7439-89-6], KClO4: [7778-74-7], Viton: [9011-17-0].

关键词： Barium chromate Heat-powder Iron Lithium Molten salt Potassium perchlorate Pyrotechnics Thermal battery Zirconium

Using coalgebras and the Giry monad for interpreting game logics a tutorial

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Frontiers of Computer Science 2017年第6期11卷 948-970页

作者： ernst-Erich DOBERKAT Math++ Software Bochum 44879 Germany

The stochastic interpretation of Parikh＇s game logic should not follow the usual pattern of Kripke models, which in turn are based on the Kleisli morphisms for the Giry monad, rather, a specific and more general approach to proba- bilistic nondeterminism is required. We outline this approach together with its probabilistic and measure theoretic basis, in- troducing in a leisurely pace the Giry monad and its Kleisli morphisms together with important techniques for manipu- lating them. Proof establishing specific techniques are given, and pointers to the extant literature are provided. After working through this tutorial, the reader should find it easier to follow the original literature in this and related areas, and it should be possible for her or him to appreciate measure theoretic arguments for original work in the areas of Markov transition systems, and stochastic effectivity func- tions.

关键词： coalgebras modal logics monads Giry monad,upper closed monad composition of monads game logics

Review of Late Jurassic-early Miocene sedimentation and plate-tectonic evolution of northern California:illuminating example of an accretionary margin

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Chinese Journal Of Geochemistry 2015年第2期34卷 123-142页

作者： W.G.ernst Department of Geological & Environmental Sciences Stanford University

Production of voluminous igneous arc rocks,high-pressure/low-temperature(HP/LT) metamafic rocks,westward relative migration of the Klamath Mountains province,and U-Pb ages of deposition,sediment sources,and spatial locations of Jurassic and younger,detrital zirconbearing clastic rocks constrain geologic development of the northern California continental edge as follows:(1) At~ 175 Ma,transpressive plate underflow began to generate an Andean-type Klamath-Sierran arc along the margin.(2)Oceanic crustal rocks were metamorphosed under HP/LT conditions in an inboard,east-inclined subduction zone from~ 170-155 *** for the Red Ant blueschists,such Ethologies remained stored at depth;most HP/LT mafic tectonic blocks returned surfaceward only during mid- and Late Cretaceous time,chiefly entrained in circulating,buoyant Franciscan mud-matrix melange.(3) By ~ 165 Ma and continuing to ~ 150-140 Ma,erosion supplied volcanogenic debris to proximal Mariposa-Galice ± Myrtle overlap strata.(4) At ~ 140,immediately prior to the onset of paired Franciscan and Great Valley Group(GVG) +Hornbrook deposition,the Klamath salient was deformed and displaced ~ 100-150 km westward relative to the Sierran arc,stranding pre-existing oceanic crust on the south as the Coast Range Ophiolite(CRO).(5) After the end-ofJurassic seaward step-out of the Farallon-North American convergent plate junction,terrigineous debris began to be deposited in the outboard Franciscan trench and intervening Great Valley forearc.(6) Voluminous sedimentation and accretion of Franciscan Eastern + Central belts and GVG detritus took place during paroxysmal igneous activity and rapid,nearly orthogonal plate convergence at^125-80 Ma.(7) Sierran arc volcanism-plutonism ceased by^80 Ma in northern California,signaling a transition to shallow,nearly subhorizontal eastward plate underflow attending Laramide orogeny far to the east.(8) Presently exposed Paleogenelower Miocene Franciscan Coastal Belt sedimentary strata were

关键词：板块构造早中新世加利福尼亚州晚侏罗世增生保证金 U-Pb年龄地层沉积

Superlubricity on the nanometer scale

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Friction 2014年第2期2卷 106-113页

作者： ernst MEYER Enrico GNECCO Department of Physics University of BaselKlingelbergstr.824056 BaselSwitzerland IMDEA Nanociencia Campus Universitario de CantoblancoCalle Faraday 928049 MadridSpain

The transition from atomic stick-slip to continuous sliding has been observed in a number of *** extended contacts are moved in different directions,so-called structural lubricity is observed when the two surface lattices are ***,a“superlubric”state of motion can be achieved if the normal force is reduced below a certain threshold,the temperature is increased,or the contact is actuated *** processes have been partially demonstrated using atomic force microscopy,and they can be theoretically understood by proper modifications of the Prandtl−Tomlinson model.

关键词： structural lubricity dynamic superlubricity atomic force microscopy friction force microscopy themolubricity Prandtl−Tomlinson model

The Mechanism of Ground Granulated Blastfurnace Slag Preventing Alkali Aggregate Reaction

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Journal of Wuhan University of Technology(Materials Science) 2010年第2期25卷 332-341页

作者： STARK Jochen FREYBURG ernst F A Finger-Institute for Building Material Science of Bauhaus-University Weimar

Three different methods were applied to study the alkali content of gelpores in cement. In the closed system, the concentration of K＋, Na＋ and OH - have not reduced with the increase of age. In the open system, the diffusion and transferring of K＋ and Na＋ towards free space leads to the de-crease of total alkali content. In the micro-analysis system, the contents of K＋ and Na＋ in the first hy- drated layer of ground granulated blastfurnace slag （GBFS） are very low, while the contents of calcium and magnesium are relatively high. This phenomenon shows that the mechanism of GBFS preventing alkali aggregate reaction （AAR） is： when GBFS is dissolved by alkali medium, SiO2 and Al2O3 are dissolved into the cement matrix, then around GBFS particles form reaction rings rich in Ca2＋ and Mg^2＋, and the C-S-H gel of positive charges formed in the area repulses K＋ and Na＋, which are forced to transfer to the mortar＇s matrix, pore or mortar sample surface. The transferred K ^＋ and Na^＋ form alkali gel products with other dissolved ions, then become evenly distributed in the mortar sample and react with Ca（OH）2 in pore solutions to form （Na,K）x-2z·zCa·（SiO2）y·（OH）x gel products; and thus changes the AAR gel products＇ structure. The gel products will not expand, and so they can delay expansion destruction.

关键词： granulated blastfurnace slag (GBFS) alkali aggregate reaction (AAR) alkali content preventing mechanism