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G-quadruplex formation of oligonucleotides containing ALS and FTD related GGGGCC repeat

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Frontiers of Chemical Science and Engineering 2016年第2期10卷 222-237页

作者： Jasna Brcic janez Plavec Slovenian NMR Center National Institute of Chemistry Hajdrihova 19 SI-1000 Ljubljana Slovenia Faculty of Chemistry and Chemical Technology University of Ljubljana SI-1000 Ljubljana Slovenia EN-FiST Center of Excellence SI-1000 Ljubljana Slovenia

A largely increased number of GGGGCC repeats located in the non-coding region of C9orf72 gene have been identified as the leading cause of two related neurological disorders, familial amyotrophic lateral sclero- sis （ALS） and frontotemporal dementia （FTD）. We examined G-quadruplex forming ability of GGGGCC- repeat containing oligonucleotides with four guanine tracts chosen as the smallest possible model to form a unimolecular G-quadruplex. These oligonucleotides are readily to folded into G-quadruplexes in the presence of K~ ions. However, the formation of multiple structures makes structural analysis challenging and time consuming. We observed that flanking sequences on 5＇- and 3＇-ends as well as mutations of loop residues have a profound effect on folding. Sequence d[（GaC2）3G4] was chosen for further scrutiny and optimization of nuclear magnetic resonance （NMR） spectroscopic properties with dG to 8Br-dG substitutions at specific positions in the sequence under different folding conditions. Expectedly, folding into desired predominant topology is facilitated when sub- stituted residue adopted a syn conformation in the naturally-occurring structure. Single dG to 8Br-dG sub- stitution at position 21 and fine tuning of folding conditions facilitate folding of d[（G4C2）3GG^BrGG] into （mostly） a single G-quadruplex, and thus enable determi- nation of its high-resolution structure by high-field NMR.

关键词： G-quadruplex GGGGCC NMR ALS/FTD,polymorphism

identification of neurological disease targets of natural products by computational screening

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Neural Regeneration Research 2019年第12期14卷 2075-2076页

作者： janez Konc Theory Department National Institute of Chemistry

The development of new drugs is traditionally focused on a single target protein. Only recently has it been recognized that drugs, i.e., small molecules, usually bind to several target proteins and thus have a wider spectrum of different effects (Konc, 2019). Natural substances are very interesting in this respect, as more than 32% of all drugs on the market today are derived from natural sources. However, natural substances are largely unexplored as their exact mechanisms of action are often unknown (Baran, 2018). in order to determine their actions, we can resort to computational methods. Computational screening enables the identification of potential target proteins, the explanation of observed effects and the prediction of novel effects of natural compounds. Computer algorithms enable targeted investigations, such as focused experimental tests on a specific target protein or a family of potential target proteins.

关键词： identification natural products The development

Differences in nano-topography and tribochemistry of ZDDP tribofilms from variations in contact configuration with steel and DLC surfaces

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Friction 2022年第2期10卷 296-315页

作者： Lucija COGA Somayeh AKBARi janez KOVA Mitjan KALiN NanoSciTec GmbH Munich 80687Germany Department of Surface Engineering and Optoelectronics Jo?ef Stefan InstituteLjubljana 1000Slovenia Laboratory for Tribology and interface Nanotechnology Faculty of Mechanical EngineeringUniversity of LjubljanaLjubljana 1000Slovenia

in this work,we evaluated the effect of the counter-body material(the same or dissimilar)and contact configuration(moving or stationary body),at similar contact tribological conditions,on the tribochemical and nanotopography characteristics of adsorbed surface *** dialkyldithiophosphate(ZDDP),the best performing anti-wear additive,was used in self-mated steel/steel and DLC/DLC contacts,which were compared with mixed steel/DLC and DLC/steel contacts in 1-h and 6-h sliding *** macroscale(tribometer)and nanoscale(atomic force microscopy)friction,thickness,topography,and chemical(attenuated total reflection-Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy)properties of the tribofilms were *** results revealed unexpectedly large differences in all the studied tribofilm parameters;this is because all the tribofilms are completely different;this includes the chemical composition,which is known to have a crucial effect on the nano-and macro-scale tribological *** results clearly demonstrate that the surface material,additives,and common contact operating parameters,that is,pressure,velocity,and temperature,crucially affect the ZDDP tribofilm as well as the position of the moving or stationary surface within the contact,and the material of the moving/stationary bodies.

关键词： dithiophosphate(ZDDP) diamond-like carbon(DLC) steel tribofilm tribochemistry nano-friction thickness topography

Laser Cladding of Cold-Work Tool Steel by Pulse Shaping

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Journal of Materials Science & Technology 2011年第8期27卷 707-713页

作者： Matej Pleterski janez Tuek Tadej Muhic Ladislav Kosec Faculty of Mechanical Engineering University of Ljubljana Akereva cesta 6 TKC D.O.O. Trnovska Ulica 8 Faculty of Natural Sciences and Engineering University of Ljubljana Akereva Cesta 12

Repair welding of cold-work tool steels in cold is very risky and almost impossible by conventional processes. The application of pulse shaping in laser cladding with wire to avoid the solidification problems in relevant steel is demonstrated. The results show that sound remelting and/or cladding can be achieved by the right selection of laser parameters and pulse shape, i.e. long pulse duration, moderate pulse peak powers and ramped-down pulse shape. Despite the defects and softening in the cladding due to the formation of retained austenite, the cladding shows better wear resistance at lower loads compared to the heat-treated base material.

关键词： Laser cladding Repair welding Tool steel Wear test

Governance of change for sustainability: experience from Central and Eastern Europe

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Ecosystem Health and Sustainability 2015年第8期1卷 11-13页

作者： janez Potocnik Co-Chair of UNEP international Resource Panel and former European Commissioner for Environment.United Nations Environment Programme15 rue de Milan75441 ParisCedex 09France

Since the first industrial revolution in the United Kingdom,the transition from agricultural and rural societies to modern urbanized economies has had vast environmental and social *** growth and changes in living standards have been accompanied by steady developments in systems of governance in order to avoid collectively detrimental outcomes and favor socially desirable ones.

关键词： Eastern collective revolution

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Journal of Thermal Science 2001年第2期10卷 164-169页

作者： janez.Jiang SuiLin Flomericsinc.Marlborough MAUSA Dept.ofMechanicalEngineeringConcordiaUniversity MontrealQuebecCanad

A similarity equation for heat transfer on heat source elements situated in the entrance region in electronic equipment is developed based on the experimental data obtained by Sparrow et al.[4]. The characteristic of the similarity equation is that the ratio of the heat transfer coefficient at the entrance region to be at the fully developed region is independent of the Reynolds number. it depends only on the row number of the elements situated in the entrance region. An example of the usefulness of the similarity equation is presented that determines the heat transfer on heat source elements in a power unit that contains only a small number of the heat source elements.

关键词： similarity equation heat transfer elctronic equipment.

Extended Global Convergence Framework for Unconstrained Optimization

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Acta Mathematica Sinica,English Series 2004年第3期20卷 433-440页

作者： rpád BRMEN Franc BRATKOVi janez PUHAN iztok FAJFAR Tadej TUMA University of Ljubljana Faculty of Electrical EngineeringTr■aka Cesta 25SI-1000 LjubljanaSlovenia

An extension of the global convergence framework for unconstrained derivative-free op- timization methods is *** extension makes it possible for the framework to include opti- mization methods with varying cardinality of the ordered direction ***-based search methods are shown to be a special case of the more general extended global convergence ***, the required properties of the sequence of ordered direction sets listed in the definition of grid-based methods are relaxed and simplified by removing the requirement of structural equivalence.

关键词： Derivative free optimization Descent methods Convergence analysis Grid-based optimization