396 results on '"Lüthi A"'
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2. Alfred Werner Fund Master’s Student Scholarships
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Hans Peter Lüthi
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Chemistry ,QD1-999 - Published
- 2023
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3. Talent meets Industry – Industry Meets Talent
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Hans Peter Lüthi and Bernardita Chirino Chace
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Chemistry ,QD1-999 - Published
- 2023
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4. SCS Spring School on Digital Chemistry 2023
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Torsten Luksch, Hans Peter Lüthi, Bálint Tamás, and Lisa Johannknecht
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Chemistry ,QD1-999 - Published
- 2023
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5. Editorial
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Hans Peter Lüthi and Roger Alberto
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Chemistry ,QD1-999 - Published
- 2023
6. SCS Annual Report 2022
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David Spichiger, Céline Wittwer, Christian Bochet, Hans Peter Lüthi, and Gillian Harvey
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Chemistry ,QD1-999 - Published
- 2023
7. Alfred Werner Fund Master’s Student Scholarships
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Hans Peter Lüthi
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Chemistry ,QD1-999 - Published
- 2022
8. Talent meets Industry – Industry meets Talent: The first online Meet&Greet Event with the Alfred Werner Scholars hosted by Novartis Pharma AG
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Hans-Peter Lüthi, Fabrice Gallou, and Arnaud Grandeury
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Chemistry ,QD1-999 - Published
- 2022
9. Meet & Greet 2022: The Alfred Werner Scholars at the Givaudan Innovation Campus in Kemptthal
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Hans Peter Lüthi and Markus Gautschi
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Chemistry ,QD1-999 - Published
- 2022
10. Swiss Summer School on Chemical Biology, Les Diablerets, September 11-15, 2022
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Hans Peter Lüthi, Jean-Louis Reymond, Marié-Désirée Scheidt, Mario de Capitano, Marina Russo, and Jiajun Ren
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Chemistry ,QD1-999 - Published
- 2022
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11. Editorial
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Eva Hevia and Hans Peter Lüthi
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Chemistry ,QD1-999 - Published
- 2022
12. SCS Fall Meeting 2019, General Information
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R. Alberto and H. P. Lüthi
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Chemistry ,QD1-999 - Published
- 2019
13. Multi-Resolution SPH Simulation of a Laser Powder Bed Fusion Additive Manufacturing Process
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Mohamadreza Afrasiabi, Christof Lüthi, Markus Bambach, and Konrad Wegener
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additive manufacturing ,LPBF ,numerical simulation ,SPH ,particle refinement ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
This paper presents an efficient mesoscale simulation of a Laser Powder Bed Fusion (LPBF) process using the Smoothed Particle Hydrodynamics (SPH) method. The efficiency lies in reducing the computational effort via spatial adaptivity, for which a dynamic particle refinement pattern with an optimized neighbor-search algorithm is used. The melt pool dynamics is modeled by resolving the thermal, mechanical, and material fields in a single laser track application. After validating the solver by two benchmark tests where analytical and experimental data are available, we simulate a single-track LPBF process by adopting SPH in multi resolutions. The LPBF simulation results show that the proposed adaptive refinement with and without an optimized neighbor-search approach saves almost 50% and 35% of the SPH calculation time, respectively. This achievement enables several opportunities for parametric studies and running high-resolution models with less computational effort.
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- 2021
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14. Toward reliable and accessible ammonia quantification in the electrocatalytic reduction of nitrogen
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Florentine L. P. Veenstra, Javier Pérez-Ramírez, René Verel, James Lüthi, and Antonio J. Martín
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business.industry ,Organic Chemistry ,chemistry.chemical_element ,Electrocatalyst ,Nitrogen ,Catalysis ,Reduction (complexity) ,Ammonia ,chemistry.chemical_compound ,chemistry ,Chemistry (miscellaneous) ,Scientific method ,Environmental science ,Physical and Theoretical Chemistry ,Process engineering ,business - Abstract
Summary Nitrogen electroreduction may alleviate fossil energy requirements to produce fertilizers, but efficient catalysts must still be developed. The development of accurate and accessible ammonia quantification tools is key to accelerate this process. This article provides guidelines to optimize sensitivity of UV-vis spectroscopy and the ion-selective electrode for initial catalyst screening. However, confirmation of the catalytic origin of ammonia is only feasible through 1H-NMR, which is much less frequently applied largely due to the high expertise and expensive apparatuses needed. We introduce a protocol accessible to catalyst practitioners applicable to widely available 300 MHz NMR spectrometers. To this end, we adapted the WATERGATE suppression method to accomplish high signal-to-noise ratios even in non-deuterated samples. It was demonstrated for a relevant concentration of 1 ppm, enabling qualitative and quantitative analysis in 2 and 15 min, respectively. By making 1H-NMR quantification more accessible, this study facilitates the application of state-of-the-art catalytic assessments.
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- 2021
15. Schiff Base Ancillary Ligands in Bis(diimine) Copper(I) Dye-Sensitized Solar Cells
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Elias Lüthi, Paola Andrea Forero Cortés, Alessandro Prescimone, Edwin C. Constable, and Catherine E. Housecroft
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copper ,dye-sensitized solar cell ,schiff base ,phosphonic acid ,crystal structure ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Five 6,6′-dimethyl-2,2′-bipyridine ligands bearing N-arylmethaniminyl substituents in the 4- and 4′-positions were prepared by Schiff base condensation in which the aryl group is Ph (1), 4-tolyl (2), 4-tBuC6H4 (3), 4-MeOC6H4 (4), and 4-Me2NC6H4 (5). The homoleptic copper(I) complexes [CuL2][PF6] (L = 1−5) were synthesized and characterized, and the single crystal structure of [Cu(1)2][PF6]·Et2O was determined. By using the “surfaces-as-ligands, surfaces-as-complexes” (SALSAC) approach, the heteroleptic complexes [Cu(6)(Lancillary)]+ in which 6 is the anchoring ligand ((6,6′-dimethyl-[2,2′-bipyridine]-4,4′-diyl)bis(4,1-phenylene))bis(phosphonic acid)) and Lancillary = 1−5 were assembled on FTO-TiO2 electrodes and incorporated as dyes into n-type dye-sensitized solar cells (DSCs). Data from triplicate, fully-masked DSCs for each dye revealed that the best-performing sensitizer is [Cu(6)(1)]+, which exhibits photoconversion efficiencies (η) of up to 1.51% compared to 5.74% for the standard reference dye N719. The introduction of the electron-donating MeO and Me2N groups (Lancillary = 4 and 5) is detrimental, leading to a decrease in the short-circuit current densities and external quantum efficiencies of the solar cells. In addition, a significant loss in open-circuit voltage is observed for DSCs sensitized with [Cu(6)(5)]+, which contributes to low values of η for this dye. Comparisons between performances of DSCs containing [Cu(6)(1)]+ and [Cu(6)(4)]+ with those sensitized by analogous dyes lacking the imine bond indicate that the latter prevents efficient electron transfer across the dye.
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- 2020
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16. Preparation and Machine-Learning Methods of Nacre-like Composites from the Self-Assembly of Magnetic Colloids Exposed to Rotating Magnetic Fields
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Antonia Neels, Marco Furlan, Thomas Lüthi, Marco Lattuada, Jürgen Hofmann, Miroslava Nedyalkova, and Joelle Medinger
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Toughness ,Rotating magnetic field ,Materials science ,business.industry ,Silica gel ,Composite number ,Modulus ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Machine learning ,computer.software_genre ,Elastomer ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Phase (matter) ,General Materials Science ,Artificial intelligence ,Composite material ,0210 nano-technology ,Porosity ,business ,computer - Abstract
Composite materials designed by nature, such as nacre, can display unique mechanical properties and have therefore been often mimicked by scientists. In this work, we prepared composite materials mimicking the nacre structure in two steps. First, we synthesized a silica gel skeleton with a layered structure using a bottom-up approach by modifying a sol-gel synthesis. Magnetic colloids were added to the sol solution, and a rotating magnetic field was applied during the sol-gel transition. When exposed to a rotating magnetic field, magnetic colloids organize in layers parallel to the plane of rotation of the field and template the growing silica phase, resulting in a layered anisotropic silica network mimicking the nacre's inorganic phase. Heat treatment has been applied to further harden the silica monoliths. The final nacre-inspired composite is created by filling the porous structure with a monomer, leading to a soft elastomer upon polymerization. Compression tests of the platelet-structured composite show that the mechanical properties of the nacre-like composite material far exceed those of nonstructured composite materials with an identical chemical composition. Increased toughness and a nearly 10-fold increase in Young's modulus were achieved. The natural brittleness and low elastic deformation of silica monoliths could be overcome by mimicking the natural architecture of nacre. Pattern recognition obtained with a classification of machine learning algorithms was applied to achieve a better understanding of the physical and chemical parameters that have the highest impact on the mechanical properties of the monoliths. Multivariate statistical analysis was performed to show that the structural control and the heat treatment have a very strong influence on the mechanical properties of the monoliths.
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- 2021
17. Alfred Werner Fund, Master’s Student Scholarships
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H.P. Lüthi
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Chemistry ,QD1-999 - Published
- 2017
18. PD Dr. Hans Peter Lüthi
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H. P. Lüthi
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Chemistry ,QD1-999 - Published
- 2017
19. The polarized localization of lipoprotein receptors and cholesterol transporters in the syncytiotrophoblast of the placenta is reproducible in a monolayer of primary human trophoblasts
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Christiane Albrecht, Bárbara Fuenzalida, Andrea Leiva, Sampada Kallol, and Michael Lüthi
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Adult ,Lipoproteins ,Placenta ,chemistry.chemical_compound ,Syncytiotrophoblast ,Pregnancy ,medicine ,Humans ,Scavenger receptor ,Receptors, Lipoprotein ,biology ,Cholesterol ,nutritional and metabolic diseases ,Obstetrics and Gynecology ,Biological Transport ,Apical membrane ,Trophoblasts ,Cell biology ,medicine.anatomical_structure ,Reproductive Medicine ,chemistry ,ABCA1 ,LDL receptor ,biology.protein ,Female ,lipids (amino acids, peptides, and proteins) ,Developmental Biology ,Lipoprotein - Abstract
Introduction The uptake of low- and high-density lipoproteins (LDL and HDL) through the LDL receptor (LDLR) and the scavenger receptor class B type I (SR-BI) mediates maternal to fetal cholesterol transfer in syncytiotrophoblast (STB) cells. STB cells deliver cholesterol via cholesterol efflux through the ATP-binding cassette transporters A1 (ABCA1, to ApoA-I), G1 (ABCG1, to HDL), and SR-BI (to HDL). In the human placenta, these proteins are localized in the apical (LDLR, SR-BI, ABCA1) and basal (SR-BI, ABCA1, ABCG1) membrane of STB cells. However, whether these proteins in polarized primary culture models of STB show a similar localization to those in the human placenta is currently unknown. Methods Primary human trophoblasts (PHT) were isolated from normal placentas and cultured in Transwells® with Matrigel to obtain a polarized STB monolayer, proteins were determined by immunofluorescence and cholesterol efflux determined to different acceptors. Results At day 5, LDLR and ABCA1 localized mainly in the apical membrane, ABCG1 in the basal membrane, and SR-BI in both. Cholesterol efflux towards the apical compartment was higher to adult and neonatal HDL compared to ApoA-I. When acceptors were added in the basal compartment, cholesterol was retained in the Matrigel. Discussion Polarized STB monolayers express LDLR, SR-BI, ABCA1 and ABCG1, and their apical/basal localization resembles the one described in human placental tissue. This study confirms the high physiological value and suitability of this model for use in functional studies. Our findings also suggest that ABCA1 and SR-BI participate in cholesterol efflux to the maternal side of the cells.
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- 2021
20. Alfred Werner Fund, Master's Student Scholarships
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Hans Peter Lüthi
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Chemistry ,QD1-999 - Published
- 2021
21. Establishment of a Mass-Spectrometry-Based Method for the Identification of the In Vivo Whole Blood and Plasma ADP-Ribosylomes
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Giody Bartolomei, Christine Neupert, Anna Howald, Robert Graage, Stephanie C Lüthi, Xaver Sidler, Michael O. Hottiger, Deena M. Leslie Pedrioli, Kathrin Nowak, University of Zurich, and Hottiger, Michael O
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0301 basic medicine ,1303 Biochemistry ,ADP-ribosylation ,systemic inflammatory response syndrome ,sepsis ,blood ,plasma ,histidine ADP-ribosylation ,1600 General Chemistry ,Biochemistry ,Sepsis ,03 medical and health sciences ,In vivo ,medicine ,Whole blood ,chemistry.chemical_classification ,030102 biochemistry & molecular biology ,Phosphodiesterase ,General Chemistry ,medicine.disease ,10226 Department of Molecular Mechanisms of Disease ,Blood proteins ,In vitro ,3. Good health ,10187 Department of Farm Animals ,030104 developmental biology ,Enzyme ,chemistry ,570 Life sciences ,biology - Abstract
Blood and plasma proteins are heavily investigated as biomarkers for different diseases. However, the post-translational modification states of these proteins are rarely analyzed since blood contains many enzymes that rapidly remove these modifications after sampling. In contrast to the well-described role of protein ADP-ribosylation in cells and organs, its role in blood remains mostly uncharacterized. Here, we discovered that plasma phosphodiesterases and/or ADP-ribosylhydrolases rapidly demodify in vitro ADP-ribosylated proteins. Thus, to identify the in vivo whole blood and plasma ADP-ribosylomes, we established a mass-spectrometry-based workflow that was applied to blood samples collected from LPS-treated pigs (Sus scrofa domesticus), which serves as a model for human systemic inflammatory response syndrome. These analyses identified 60 ADP-ribosylated proteins, 17 of which were ADP-ribosylated plasma proteins. This new protocol provides an important step forward for the rapidly developing field of ADP-ribosylation and defines the blood and plasma ADP-ribosylomes under both healthy and disease conditions., Journal of Proteome Research, 20 (6), ISSN:1535-3893, ISSN:1535-3907
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- 2021
22. Substituent-controlled, mild oxidative fluorination of iodoarenes: synthesis and structural study of aryl I(iii)- and I(v)-fluorides† †Electronic supplementary information (ESI) available. CCDC 1913138–1913140. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c9sc02162k
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Häfliger, Joel, Pitts, Cody Ross, Bornemann, Dustin, Käser, Roland, Santschi, Nico, Charpentier, Julie, Otth, Elisabeth, Trapp, Nils, Verel, René, Lüthi, Hans Peter, and Togni, Antonio
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Chemistry - Abstract
This mild TCICA/KF oxidative fluorination approach provides controllable access to aryl-IF2 and aryl-IF4 compounds, thus allowing detailed structural studies., We report a mild approach to the synthesis of difluoro(aryl)-λ3-iodanes (aryl-IF2 compounds) and tetrafluoro(aryl)-λ5-iodanes (aryl-IF4 compounds) using trichloroisocyanuric acid (TCICA) and potassium fluoride (KF). Under these reaction conditions, selective access to either the I(iii)- or I(v)-derivatives is predictable based solely on the substitution pattern of the iodoarene starting material. Moreover, the discovery of this TCICA/KF approach prompted detailed dynamic NMR, kinetic, computational, and crystallographic studies on the relationship between the IF2 group and the ortho-substituents on carefully designed probe molecules. It was during these experiments that the role of the ortho-substituent in inhibiting further oxidative fluorination of I(iii)-compounds to I(v)-compounds during the reaction with TCICA and KF was revealed. Additionally, a notable exception to this empirical trend is discussed herein.
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- 2019
23. Substituent-controlled, mild oxidative fluorination of iodoarenes: synthesis and structural study of aryl I(<scp>iii</scp>)- and I(<scp>v</scp>)-fluorides
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Elisabeth Otth, Julie Charpentier, Nico Santschi, Nils Trapp, Antonio Togni, Hans Peter Lüthi, Roland Käser, René Verel, Cody Ross Pitts, Joel Häfliger, and Dustin Bornemann
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Reaction conditions ,010405 organic chemistry ,Aryl ,Substituent ,General Chemistry ,Oxidative phosphorylation ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Potassium fluoride ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Molecule ,Trichloroisocyanuric acid - Abstract
We report a mild approach to the synthesis of difluoro(aryl)-λ3-iodanes (aryl-IF2 compounds) and tetrafluoro(aryl)-λ5-iodanes (aryl-IF4 compounds) using trichloroisocyanuric acid (TCICA) and potassium fluoride (KF). Under these reaction conditions, selective access to either the I(III)- or I(V)-derivatives is predictable based solely on the substitution pattern of the iodoarene starting material. Moreover, the discovery of this TCICA/KF approach prompted detailed dynamic NMR, kinetic, computational, and crystallographic studies on the relationship between the IF2 group and the ortho-substituents on carefully designed probe molecules. It was during these experiments that the role of the ortho-substituent in inhibiting further oxidative fluorination of I(III)-compounds to I(V)-compounds during the reaction with TCICA and KF was revealed. Additionally, a notable exception to this empirical trend is discussed herein.
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- 2019
24. Editorial
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Hans Peter Lüthi and Silvio Decurtins
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Chemistry ,QD1-999 - Published
- 2021
25. Optogenetic silencing of neurotransmitter release with a naturally occurring invertebrate rhodopsin
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Anna Litvin, Mauro Pulin, Dietmar Schmitz, Ofer Yizhar, Inbar Saraf-Sinik, Andreas Lüthi, Asaf Gat, Shaked Palgi, Eyal Bitton, Nikolaos Karalis, Mathias Mahn, Jonas Wietek, Julien Dine, J. Simon Wiegert, Ido Davidi, Benjamin R. Rost, Fangmin Zhou, Rivka Levy, Felicitas Bruentgens, Pritish Patil, Kathrin Sauter, and Peter Soba
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chemistry.chemical_compound ,chemistry ,biology ,In vivo ,Rhodopsin ,Dopaminergic ,biology.protein ,Encephalopsin ,Signal transduction ,Neurotransmission ,Optogenetics ,Neurotransmitter ,Neuroscience - Abstract
Information is carried between brain regions through neurotransmitter release from axonal presynaptic terminals. Understanding the functional roles of defined neuronal projection pathways in cognitive and behavioral processes requires temporally precise manipulation of their activity in vivo. However, existing optogenetic tools have low efficacy and off-target effects when applied to presynaptic terminals, while chemogenetic tools are difficult to control in space and time. Here, we show that a targeting-enhanced mosquito homologue of the vertebrate encephalopsin (eOPN3) can effectively suppress synaptic transmission through the Gi/o signaling pathway. Brief illumination of presynaptic terminals expressing eOPN3 triggers a lasting suppression of synaptic output that recovers spontaneously within minutes in vitro as well as in vivo. In freely moving mice, eOPN3-mediated suppression of dopaminergic nigrostriatal afferents leads to an ipsiversive rotational bias. We conclude that eOPN3 can be used to selectively suppress neurotransmitter release at synaptic terminals with high spatiotemporal precision, opening new avenues for functional interrogation of long-range neuronal circuits in vivo.
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- 2021
26. Swiss Summer School 2021: Catalysis and Sustainable Chemistry
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Hans P. Lüthi, Marie Francine Lagadec, Lauren Gamp, Céline Wittwer, Bill Morandi, and Jérome Waser
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Chemistry ,QD1-999 - Abstract
Chimia, 75 (12), ISSN:0009-4293
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- 2021
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27. SCS Fall Meeting 2020: A Success Story Based on 'Plan B'
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Hans Peter, Lüthi, Silvio, Decurtins, David, Spichiger, and Céline, Wittwer
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Chemistry ,Fall meeting 2020 ,Swiss chemical society ,QD1-999 - Published
- 2020
28. Editorial
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David Spichiger, Hans P. Lüthi, and Guido Koch
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Chemistry ,QD1-999 - Published
- 2020
29. Association of urinary sex steroid hormones with urinary calcium, oxalate and citrate excretion in kidney stone formers
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Nasser A. Dhayat, Daniel Guido Fuster, Cedric Mattmann, Gaétan A Morard, Lisa Schneider, Bruno Vogt, and David Lüthi
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0301 basic medicine ,Male ,medicine.medical_specialty ,Urinary system ,030232 urology & nephrology ,Dehydroepiandrosterone ,610 Medicine & health ,Citric Acid ,Excretion ,03 medical and health sciences ,chemistry.chemical_compound ,Kidney Calculi ,0302 clinical medicine ,Sex hormone-binding globulin ,Internal medicine ,Medicine ,Humans ,Citrates ,Gonadal Steroid Hormones ,Transplantation ,Oxalates ,Androsterone ,biology ,business.industry ,Estriol ,medicine.disease ,Urinary calcium ,030104 developmental biology ,Endocrinology ,Cross-Sectional Studies ,chemistry ,Nephrology ,biology.protein ,Kidney stones ,Calcium ,Female ,business - Abstract
Background Sex-specific differences in nephrolithiasis with respect to both distribution of prevalence and stone composition are widely described and may be influenced by sex hormones. Methods We conducted a cross-sectional analysis of the relationship between 24-h urinary sex hormone metabolites measured by gas chromatography–mass spectrometry with urinary calcium, oxalate and citrate excretion in a cohort of 628 kidney stone formers from a tertiary care hospital in Switzerland, taking demographic characteristics, kidney function and dietary factors into account. Results We observed a positive association of urinary calcium with urinary testosterone and 17β-oestradiol. Positive associations of urinary calcium with dehydroepiandrosterone (DHEA), 5α-DH-testosterone, aetiocholanolone, androsterone and oestriol were modified by net gastrointestinal alkali absorption or urinary sulphate excretion. As the only sex hormone, DHEA was inversely associated with urinary oxalate excretion in adjusted analyses. Urinary citrate correlated positively with urinary testosterone. Associations of urinary citrate with urinary androsterone, 17β-oestradiol and oestriol were modified by urinary sulphate or sodium or by sex. Conclusions Urinary androgens and oestrogens are significantly associated with urinary calcium and citrate excretion and associations are modified in part by diet. Our data furthermore reveal DHEA as a novel factor associated with urinary oxalate excretion in humans.
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- 2020
30. TNIK signaling imprints CD8+ T cell memory formation early after priming
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Carla A. Jaeger-Ruckstuhl, Colin Correnti, Christian M. Schürch, Stefan Freigang, Olivier Friedli, Sabine Höpner, Magdalena Hinterbrandner, Ramin Radpour, Mohamad F. Al Sayed, Adrian F. Ochsenbein, Ursina Lüthi, Elias D. Bührer, Michael A. Amrein, and Carsten Riether
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0301 basic medicine ,Science ,T cell ,Cellular differentiation ,General Physics and Astronomy ,Priming (immunology) ,610 Medicine & health ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Asymmetric cell division ,Cytotoxic T cell ,Multidisciplinary ,Chemistry ,Wnt signaling pathway ,General Chemistry ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,TNIK ,570 Life sciences ,biology ,CD8 ,030215 immunology - Abstract
Co-stimulatory signals, cytokines and transcription factors regulate the balance between effector and memory cell differentiation during T cell activation. Here, we analyse the role of the TRAF2-/NCK-interacting kinase (TNIK), a signaling molecule downstream of the tumor necrosis factor superfamily receptors such as CD27, in the regulation of CD8+ T cell fate during acute infection with lymphocytic choriomeningitis virus. Priming of CD8+ T cells induces a TNIK-dependent nuclear translocation of β-catenin with consecutive Wnt pathway activation. TNIK-deficiency during T cell activation results in enhanced differentiation towards effector cells, glycolysis and apoptosis. TNIK signaling enriches for memory precursors by favouring symmetric over asymmetric cell division. This enlarges the pool of memory CD8+ T cells and increases their capacity to expand after re-infection in serial re-transplantation experiments. These findings reveal that TNIK is an important regulator of effector and memory T cell differentiation and induces a population of stem cell-like memory T cells.
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- 2020
31. Editorial
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Hans Peter Lüthi and Roger Alberto
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Chemistry ,QD1-999 - Published
- 2020
32. Schiff Base Ancillary Ligands in Bis(diimine) Copper(I) Dye-Sensitized Solar Cells
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Alessandro Prescimone, Paola Andrea Forero Cortés, Catherine E. Housecroft, Edwin C. Constable, and Elias Lüthi
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crystal structure ,phosphonic acid ,Phosphorous Acids ,Imine ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,Catalysis ,Inorganic Chemistry ,lcsh:Chemistry ,chemistry.chemical_compound ,Electron transfer ,Polymer chemistry ,dye-sensitized solar cell ,Physical and Theoretical Chemistry ,Homoleptic ,Molecular Biology ,lcsh:QH301-705.5 ,Schiff Bases ,Spectroscopy ,Diimine ,Schiff base ,Ligand ,Aryl ,Organic Chemistry ,General Medicine ,schiff base ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Computer Science Applications ,Dye-sensitized solar cell ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,copper ,0210 nano-technology - Abstract
Five 6,6&rsquo, dimethyl-2,2&rsquo, bipyridine ligands bearing N-arylmethaniminyl substituents in the 4- and 4&rsquo, positions were prepared by Schiff base condensation in which the aryl group is Ph (1), 4-tolyl (2), 4-tBuC6H4 (3), 4-MeOC6H4 (4), and 4-Me2NC6H4 (5). The homoleptic copper(I) complexes [CuL2][PF6] (L = 1&ndash, 5) were synthesized and characterized, and the single crystal structure of [Cu(1)2][PF6].Et2O was determined. By using the &ldquo, surfaces-as-ligands, surfaces-as-complexes&rdquo, (SALSAC) approach, the heteroleptic complexes [Cu(6)(Lancillary)]+ in which 6 is the anchoring ligand ((6,6&rsquo, dimethyl-[2,2&rsquo, bipyridine]-4,4&rsquo, diyl)bis(4,1-phenylene))bis(phosphonic acid)) and Lancillary = 1&ndash, 5 were assembled on FTO-TiO2 electrodes and incorporated as dyes into n-type dye-sensitized solar cells (DSCs). Data from triplicate, fully-masked DSCs for each dye revealed that the best-performing sensitizer is [Cu(6)(1)]+, which exhibits photoconversion efficiencies (&eta, ) of up to 1.51% compared to 5.74% for the standard reference dye N719. The introduction of the electron-donating MeO and Me2N groups (Lancillary = 4 and 5) is detrimental, leading to a decrease in the short-circuit current densities and external quantum efficiencies of the solar cells. In addition, a significant loss in open-circuit voltage is observed for DSCs sensitized with [Cu(6)(5)]+, which contributes to low values of &eta, for this dye. Comparisons between performances of DSCs containing [Cu(6)(1)]+ and [Cu(6)(4)]+ with those sensitized by analogous dyes lacking the imine bond indicate that the latter prevents efficient electron transfer across the dye.
- Published
- 2020
33. Genetic, cellular and structural characterization of the membrane potential-dependent cell-penetrating peptide translocation pore
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Julien Puyal, Evgeniya Trofimenko, Francesca Amati, Marco Agostino Deriu, Yoan Arribat, Gianvito Grasso, Gilles Dubuis, Florine Ory, Mathieu Heulot, Lihn Chi Dam, Anita Lüthi, Andrea Danani, Sébastien Michel, Marc Serulla, Christian Widmann, Nadja Chevalier, and Gil Vantomme
- Subjects
cell-penetrating peptides ,Potassium Channels ,Mouse ,Animals ,Cell Line ,Cell-Penetrating Peptides/chemistry ,Cell-Penetrating Peptides/genetics ,Cell-Penetrating Peptides/metabolism ,HeLa Cells ,Humans ,Membrane Potentials ,Mice ,Mice, Inbred C57BL ,Potassium Channels/genetics ,Potassium Channels/metabolism ,Protein Transport ,Rats ,Rats, Sprague-Dawley ,Zebrafish ,In silico modeling ,TAT ,cell biology ,membrane potential ,mouse ,potassium channels ,water pores ,zebrafish ,Cell ,Chromosomal translocation ,01 natural sciences ,Biology (General) ,Internalization ,media_common ,Membrane potential ,0303 health sciences ,Chemistry ,General Neuroscience ,General Medicine ,Potassium channel ,medicine.anatomical_structure ,Membrane ,Medicine ,Intracellular ,Research Article ,QH301-705.5 ,Science ,In silico ,media_common.quotation_subject ,010402 general chemistry ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,medicine ,030304 developmental biology ,General Immunology and Microbiology ,Cell Biology ,In vitro ,0104 chemical sciences ,Cell-penetrating peptide ,Biophysics - Abstract
Cell-penetrating peptides (CPPs) allow intracellular delivery of bioactive cargo molecules. The mechanisms allowing CPPs to enter cells are ill-defined. Using a CRISPR/Cas9-based screening, we discovered that KCNQ5, KCNN4, and KCNK5 potassium channels positively modulate cationic CPP direct translocation into cells by decreasing the transmembrane potential (Vm). These findings provide the first unbiased genetic validation of the role of Vm in CPP translocation in cells. In silico modeling and live cell experiments indicate that CPPs, by bringing positive charges on the outer surface of the plasma membrane, decrease the Vm to very low values (–150 mV or less), a situation we have coined megapolarization that then triggers formation of water pores used by CPPs to enter cells. Megapolarization lowers the free energy barrier associated with CPP membrane translocation. Using dyes of varying dimensions in CPP co-entry experiments, the diameter of the water pores in living cells was estimated to be 2 (–5) nm, in accordance with the structural characteristics of the pores predicted by in silico modeling. Pharmacological manipulation to lower transmembrane potential boosted CPP cellular internalization in zebrafish and mouse models. Besides identifying the first proteins that regulate CPP translocation, this work characterized key mechanistic steps used by CPPs to cross cellular membranes. This opens the ground for strategies aimed at improving the ability of cells to capture CPP-linked cargos in vitro and in vivo., eLife digest Before a drug can have its desired effect, it must reach its target tissue or organ, and enter its cells. This is not easy because cells are surrounded by the plasma membrane, a fat-based barrier that separates the cell from its external environment. The plasma membrane contains proteins that act as channels, shuttling specific molecules in and out of the cell, and it also holds charge, with its inside surface being more negatively charged than its outside surface. Cell-penetrating peptides are short sequences of amino acids (the building blocks that form proteins) that carry positive charges. These positive charges allow them to cross the membrane easily, but it is not well understood how. To find out how cell-penetrating peptides cross the membrane, Trofimenko et al. attached them to dyes of different sizes. This revealed that the cell-penetrating peptides enter the cell through temporary holes called water pores, which measure about two nanometres across. The water pores form when the membrane becomes ‘megapolarized’, this is, when the difference in charge between the inside and the outside of the membrane becomes greater than normal. This can happen when the negative charge on the inside surface or the positive charge on the outer surface of the membrane increase. Megapolarization depends on potassium channels, which transport positive potassium ions outside the cell, making the outside of the membrane positive. When cell-penetrating peptides arrive at the outer surface of the cell near potassium channels, they make it even more positive. This increases the charge difference between the inside and the outside of the cell, allowing water pores to form. Once the peptides pass through the pores, the charge difference between the inside and the outside of the cell membrane dissipates, and the pores collapse. Drug developers are experimenting with attaching cell-penetrating peptides to drugs to help them get inside their target cells. Currently there are several experimental medications of this kind in clinical trials. Understanding how these peptides gain entry, and what size of molecule they could carry with them, provides solid ground for further drug development.
- Published
- 2020
34. Astrocytes integrate and drive action potential firing in inhibitory subnetworks
- Author
-
Joel Lüthi, Nelson Spruston, Tara Deemyad, University of Zurich, and Spruston, Nelson
- Subjects
0301 basic medicine ,Light ,Science ,Models, Neurological ,Action Potentials ,Glutamic Acid ,General Physics and Astronomy ,1600 General Chemistry ,Genetics and Molecular Biology ,Stimulation ,Optogenetics ,Inhibitory postsynaptic potential ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,1300 General Biochemistry, Genetics and Molecular Biology ,Interneurons ,medicine ,Animals ,Calcium Signaling ,lcsh:Science ,gamma-Aminobutyric Acid ,Calcium signaling ,Multidisciplinary ,Artificial neural network ,Chemistry ,Depolarization ,General Chemistry ,10124 Institute of Molecular Life Sciences ,3100 General Physics and Astronomy ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Metabotropic glutamate receptor ,Astrocytes ,General Biochemistry ,570 Life sciences ,biology ,Calcium ,lcsh:Q ,Nerve Net ,Neuroscience ,030217 neurology & neurosurgery ,Astrocyte - Abstract
Many brain functions depend on the ability of neural networks to temporally integrate transient inputs to produce sustained discharges. This can occur through cell-autonomous mechanisms in individual neurons and through reverberating activity in recurrently connected neural networks. We report a third mechanism involving temporal integration of neural activity by a network of astrocytes. Previously, we showed that some types of interneurons can generate long-lasting trains of action potentials (barrage firing) following repeated depolarizing stimuli. Here we show that calcium signaling in an astrocytic network correlates with barrage firing; that active depolarization of astrocyte networks by chemical or optogenetic stimulation enhances; and that chelating internal calcium, inhibiting release from internal stores, or inhibiting GABA transporters or metabotropic glutamate receptors inhibits barrage firing. Thus, networks of astrocytes influence the spatiotemporal dynamics of neural networks by directly integrating neural activity and driving barrages of action potentials in some populations of inhibitory interneurons., Specific types of inhibitory neurons exhibit prolonged, high-frequency barrages of action potentials. Here, the authors show that astrocytes might mediate such barrage firing.
- Published
- 2018
35. Exploring Machine Learning Tools for the Prediction of the Stability of New Togni-type Reagents
- Author
-
Shungo Koichi and Hans Peter Lüthi
- Subjects
Intermediate form ,Computer science ,business.industry ,Stability (learning theory) ,Context (language use) ,Togni-type reagents ,General Medicine ,General Chemistry ,Type (model theory) ,Machine learning ,computer.software_genre ,Maxima and minima ,Chemistry ,Reagent ,Artificial intelligence ,business ,computer ,QD1-999 - Abstract
In the context of the prediction of the (in-)stability of chemical compounds using machine learning tools, we are often confronted with a basic issue: Whereas much information is available on stable (existing) compounds, little is known about compounds that might well exist, but that have not yet been successfully synthesized, or compounds that are inherently unstable (kinetically and thermodynamically). In the search for Togni-type reagents, many of them kinetically instable, the stability of the prospects can be assessed based on the transition state for the conversion to their non-hypervalent inactive isomer. In earlier work, we determined the barriers of conversion for over one-hundred reagents, still not enough information to train a tool such as a vector support machine. Here, instead, we focus on the early intermediate structures expressed along the isomerization pathway, i.e. transition state searches are replaced by finding (local) minima. Based on an array of 382 Togni-type reagents whose behaviour was known in advance, we show that it is possible to have the machine predict the intermediate form expressed. The approach introduced here can be used to make predictions on the stability and possibly also the reactivity of Togni-type reagents in general.
- Published
- 2019
36. Editorial
- Author
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Torsten Luksch and Hans Peter Lüthi
- Subjects
Chemistry ,QD1-999 - Published
- 2019
37. Swiss Summer School 'Trends in Organic Synthesis' Villars-sur-Ollon, August 18–22, 2019
- Author
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Christian G. Bochet, Philippe Renaud, and Hans P. Lüthi
- Subjects
Chemistry ,QD1-999 - Published
- 2019
38. Efficient optogenetic silencing of neurotransmitter release with a mosquito rhodopsin
- Author
-
Inbar Saraf-Sinik, Pritish Patil, J. Simon Wiegert, Eyal Bitton, Nikolaos Karalis, Kathrin Sauter, Dietmar Schmitz, Ofer Yizhar, Andreas Lüthi, Peter Soba, Jonas Wietek, Julien Dine, Fangmin Zhou, Rivka Levy, Felicitas Bruentgens, Anna Litvin, Ido Davidi, Benjamin R. Rost, Asaf Gat, Mauro Pulin, Shaked Palgi, and Mathias Mahn
- Subjects
0301 basic medicine ,autaptic neurons ,genetics [Rhodopsin] ,presynaptic ,Dopamine ,physiology [Substantia Nigra] ,Rats, Sprague-Dawley ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,metabolism [Dopamine] ,metabolism [Rhodopsin] ,inhibitory ,Neurotransmitter ,Cells, Cultured ,biology ,thalamocortical ,Chemistry ,General Neuroscience ,metabolism [Dopaminergic Neurons] ,Dopaminergic ,Synaptic Potentials ,Substantia Nigra ,Rhodopsin ,metabolism [Insect Proteins] ,Insect Proteins ,Signal transduction ,Locomotion ,mosquito ,cytology [Substantia Nigra] ,Optogenetics ,Neurotransmission ,Inhibitory postsynaptic potential ,Article ,methods [Optogenetics] ,03 medical and health sciences ,GCPR ,Animals ,Humans ,ddc:610 ,G protein-coupled receptor ,Encephalopsin ,Rats, Wistar ,physiology [Dopaminergic Neurons] ,optogenetics ,dopaminergic ,eOPN3 ,Dopaminergic Neurons ,genetics [Insect Proteins] ,Rats ,Mice, Inbred C57BL ,Culicidae ,HEK293 Cells ,030104 developmental biology ,silencing ,biology.protein ,Neuroscience ,030217 neurology & neurosurgery - Abstract
HIGHLIGHTS: eOPN3 is a mosquito-derived rhodopsin that inhibits neurotransmission in neurons. Activation of eOPN3 activates the G(i/o) pathway and reduces Ca(2+) channel activity; eOPN3 can suppress neurotransmission in a variety of cell types in vitro and in vivo. Activation of eOPN3 in nigrostriatal dopamine axons modulates locomotor behavior. SUMMARY: Information is carried between brain regions through neurotransmitter release from axonal presynaptic terminals. Understanding the functional roles of defined neuronal projection pathways requires temporally precise manipulation of their activity. However, existing inhibitory optogenetic tools have low efficacy and off-target effects when applied to presynaptic terminals, while chemogenetic tools are difficult to control in space and time. Here, we show that a targeting-enhanced mosquito homolog of the vertebrate encephalopsin (eOPN3) can effectively suppress synaptic transmission through the G(i/o) signaling pathway. Brief illumination of presynaptic terminals expressing eOPN3 triggers a lasting suppression of synaptic output that recovers spontaneously within minutes in vitro and in vivo. In freely moving mice, eOPN3-mediated suppression of dopaminergic nigrostriatal afferents induces a reversible ipsiversive rotational bias. We conclude that eOPN3 can be used to selectively suppress neurotransmitter release at presynaptic terminals with high spatiotemporal precision, opening new avenues for functional interrogation of long-range neuronal circuits in vivo.
- Published
- 2021
39. Importance of Nonclassical σ-Hole Interactions for the Reactivity of λ3-Iodane Complexes
- Author
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Antonio Togni, Halua Pinto de Magalhães, and Hans Peter Lüthi
- Subjects
010405 organic chemistry ,Chemistry ,Stereochemistry ,Organic Chemistry ,Supramolecular chemistry ,Hypervalent molecule ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Crystal ,Selective transfer ,Nucleophile ,Computational chemistry ,Reagent ,Halogen ,Reactivity (chemistry) - Abstract
Key for the observed reactivity of λ3-iodanes, powerful reagents for the selective transfer of functional groups to nucleophiles, are the properties of the 3-center-4-electron bond involving the iodine atom and the two linearly arranged ligands. This bond is also involved in the formation of the initial complex between the λ3-iodane and a nucleophile, which can be a solvent molecule or a reactant. The bonding in such complexes can be described by means of σ-hole interactions. In halogen compounds, σ-hole interaction was identified as a force in crystal packing or in the formation of supramolecular chains. More recently, σ-hole interactions were also shown to affect the reactivity of the iodine-based hypervalent reagents. Relative to their monovalent counterparts, where the σ-hole is located on the extension of the sigma-bond, in the hypervalent species our DFT calculations reveal the formation of a nonclassical σ-hole region with one or even two maxima. This observation is also made in fully relativistic ...
- Published
- 2017
40. Meet & Greet Event 2019 of the Alfred Werner Scholars
- Author
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Volker Herdtweck and Hans P. Lüthi
- Subjects
Chemistry ,QD1-999 - Published
- 2019
41. Ab initio thermodynamics of carbon segregation on dislocation cores in bcc iron
- Author
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B. Lüthi, Bernard Legrand, Lisa Ventelon, David Rodney, Francois Willaime, Fabienne Berthier, CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire d'étude des matériaux hors équilibre (LEMHE), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie des Activités Physiques et Sportives (BAPS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de recherches de métallurgie physique (SRMP), Département des Matériaux pour le Nucléaire (DMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and ANR-16-CE08-0008,DeGAS,Glissement des dislocations dans les alliages : couplage chimie/microstructure(2016)
- Subjects
Materials science ,Monte Carlo method ,Binding energy ,Ab initio ,chemistry.chemical_element ,02 engineering and technology ,01 natural sciences ,Molecular physics ,Condensed Matter::Materials Science ,0103 physical sciences ,General Materials Science ,[PHYS.COND]Physics [physics]/Condensed Matter [cond-mat] ,ComputingMilieux_MISCELLANEOUS ,010302 applied physics ,[PHYS]Physics [physics] ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Computer Science Applications ,Octahedron ,chemistry ,Mechanics of Materials ,Modeling and Simulation ,[PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci] ,Ising model ,Density functional theory ,Dislocation ,0210 nano-technology ,Carbon - Abstract
The equilibrium segregation of carbon atoms in the core of screw dislocations in body-centred cubic Fe is modelled using a generalized Ising model parametrized on density functional theory calculations and solved using both mean-field calculations and Monte Carlo simulations. Recently, a strong carbon-dislocation attraction was evidenced, resulting in a spontaneous reconstruction of the dislocation core towards a hard core configuration, where the carbon atom is located at the centre of a regular trigonal prism called a prismatic site. Here we show that the fourth neighbour octahedral sites of the reconstructed core are also attractive for carbon with a binding energy similar to that of the prismatic core site reported previously. This suggests that the dislocation may be decorated by lines of carbon atoms on both types of sites. Moreover, all carbon–carbon interactions including intra-line and inter-line interactions, are found repulsive. Segregation therefore results from a competition between the dislocation-carbon attraction and the carbon–carbon repulsion, leading to complex ordering phenomena that are analysed here in detail. Notably, we evidence a high temperature regime, in the regime of dynamical strain ageing of steels, where the prismatic line is half-occupied on average with every other prismatic site occupied by a carbon atom while the octahedral lines are empty. The iso-concentrations for the prismatic and octahedral lines obtained with the mean-field approach and with Monte Carlo simulations are qualitatively similar.
- Published
- 2019
42. Abolishing cAMP sensitivity in HCN2 pacemaker channels induces generalized seizures
- Author
-
Henrik Hülle, Benedikt Zott, Saskia Spahn, Markus Moser, Manuela Brümmer, Dirk Isbrandt, Christian Gruner, Stefanie Fenske, René D. Rötzer, Andreas Ludwig, Jennifer Kass, Verena Hammelmann, Anita Lüthi, Marc Sebastian Stieglitz, Jana Hartmann, Arthur Konnerth, Karim Le Meur, Christian Wahl-Schott, and Martin Biel
- Subjects
0301 basic medicine ,Male ,Models, Molecular ,Potassium Channels ,Gating ,Epilepsy ,Mice ,0302 clinical medicine ,Thalamus ,Geniculate ,Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ,Cyclic AMP ,Neurons ,Mice, Knockout ,biology ,Behavior, Animal ,Chemistry ,General Medicine ,ddc ,medicine.anatomical_structure ,metabolism [Neurons] ,030220 oncology & carcinogenesis ,Ion channels ,metabolism [Epilepsy] ,Research Article ,metabolism [Cyclic AMP] ,metabolism [Seizures] ,03 medical and health sciences ,Hcn2 protein, mouse ,Seizures ,genetics [Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels] ,medicine ,HCN channel ,Animals ,Humans ,ddc:610 ,Protein kinase A ,Ion channel ,Behavior ,medicine.disease ,Mice, Inbred C57BL ,030104 developmental biology ,HEK293 Cells ,metabolism [Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels] ,biology.protein ,chemistry [Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels] ,metabolism [Thalamus] ,Transcriptome ,Nucleus ,Neuroscience - Abstract
Hyperpolarization-activated cyclic nucleotide–gated (HCN) channels are dually gated channels that are operated by voltage and by neurotransmitters via the cAMP system. cAMP-dependent HCN regulation has been proposed to play a key role in regulating circuit behavior in the thalamus. By analyzing a knockin mouse model (HCN2EA), in which binding of cAMP to HCN2 was abolished by 2 amino acid exchanges (R591E, T592A), we found that cAMP gating of HCN2 is essential for regulating the transition between the burst and tonic modes of firing in thalamic dorsal-lateral geniculate (dLGN) and ventrobasal (VB) nuclei. HCN2EA mice display impaired visual learning, generalized seizures of thalamic origin, and altered NREM sleep properties. VB-specific deletion of HCN2, but not of HCN4, also induced these generalized seizures of the absence type, corroborating a key role of HCN2 in this particular nucleus for controlling consciousness. Together, our data define distinct pathological phenotypes resulting from the loss of cAMP-mediated gating of a neuronal HCN channel.
- Published
- 2019
43. Fundamental Aspects of Structure, Bonding, and the Reactivity of Hypervalent Iodine Compounds
- Author
-
Hans Peter Lüthi, Halua Pinto de Magalhães, and Oliver Sala
- Subjects
Ab initio molecular dynamics ,Reaction mechanism ,Chemistry ,Computational chemistry ,Hypervalent molecule ,Reactivity (chemistry) ,Iodine compounds - Published
- 2018
44. Astrocytes integrate and drive neural activity
- Author
-
Joel Lüthi, Tara Deemyad, and Nelson Spruston
- Subjects
medicine.anatomical_structure ,nervous system ,Artificial neural network ,Chemistry ,Metabotropic glutamate receptor ,medicine ,Stimulation ,Depolarization ,Optogenetics ,Inhibitory postsynaptic potential ,Neuroscience ,Astrocyte ,Calcium signaling - Abstract
SUMMARYMany brain functions depend on the ability of neural networks to temporally integrate transient inputs to produce sustained discharges. This can occur through cell-autonomous mechanisms in individual neurons or through reverberating activity in recurrently connected neural networks. We report a third mechanism involving temporal integration of neural activity by a network of astrocytes. Previously, we showed that some types of interneurons can generate long-lasting trains of action potentials for tens of seconds (“barrage firing”) following repeated depolarizing stimuli. Here, we show that calcium signaling in an astrocytic network correlates with barrage firing; that active depolarization of astrocyte networks by chemical or optogenetic stimulation enhances barrage firing; and that chelating internal calcium, inhibiting release from internal stores, or inhibiting GABA transporters or metabotropic glutamate receptors inhibited barrage firing. Thus, through complex molecular processes, networks of interconnected astrocytes influence the spatiotemporal dynamics of neural networks by directly integrating neural activity and driving long-lasting barrages of action potentials in some populations of inhibitory interneurons.
- Published
- 2018
45. Editorial
- Author
-
Hans Peter Lüthi and Antonio Togni
- Subjects
Chemistry ,QD1-999 - Published
- 2018
46. Why do the Togni reagent and some of its derivatives exist in the high-energy hypervalent iodine form? New insight into the origins of their kinetic stability
- Author
-
Shungo Koichi, Hans Peter Lüthi, and Benjamin Leuthold
- Subjects
010405 organic chemistry ,Chemistry ,Hypervalent molecule ,Substituent ,General Physics and Astronomy ,Ether ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Bond length ,chemistry.chemical_compound ,Computational chemistry ,Reagent ,Electrophile ,Organic chemistry ,Chemical stability ,Physical and Theoretical Chemistry ,Isomerization - Abstract
In a recent study published in ChemComm, H. F. Schaefer and coworkers showed that the Togni trifluoromethyltation reagent and some of its derivatives appear in a high-energy hypervalent form. The (kinetic) stability of these reagents is granted by the five-membered ring of their benziodoxole-based scaffold, which prevents isomerization to the (inactive) acyclic ether form. Whereas the thermodynamic stability of these reagents can be predicted on the basis of the trans influence of the electrophilic substituent, no such descriptor was found for their kinetic stability. In this study, we explore an array of Togni-type reagents, and show that the barrier to isomerization can be predicted based on the bond length between the iodine atom and the electrophilic substituent. For compounds, where this correlation does not hold, we have a reliable indication that the structure of the transition state is at variance with those in the series.
- Published
- 2017
47. Dividing a complex reaction involving a hypervalent iodine reagent into three limiting mechanisms byab initiomolecular dynamics
- Author
-
Marcella Iannuzzi, Antonio Togni, Jürg Hutter, Hans Peter Lüthi, and Oliver Sala
- Subjects
Molecular Structure ,Trifluoromethylation ,Iodine Compounds ,Hypervalent molecule ,General Chemistry ,Methylation ,Reductive elimination ,Computational Mathematics ,chemistry.chemical_compound ,Phenols ,Nucleophile ,chemistry ,Computational chemistry ,Reagent ,Electrophile ,Thermodynamics ,Computer Simulation ,Nitrilium ,Solvent effects - Abstract
The electrophilic N-trifluoromethylation of MeCN with a hypervalent iodine reagent to form a nitrilium ion, that is rapidly trapped by an azole nucleophile, is thought to occur via reductive elimination (RE). A recent study showed that, depending on the solvent representation, the S(N)2 is favoured to a different extent over the RE. However, there is a discriminative solvent effect present, which calls for a statistical mechanics approach to fully account for the entropic contributions. In this study, we perform metadynamic simulations for two trifluoromethylation reactions (with N- and S-nucleophiles), showing that the RE mechanism is always favoured in MeCN solution. These computations also indicate that a radical mechanism (single electron transfer) may play an important role. The computational protocol based on accelerated molecular dynamics for the exploration of the free energy surface is transferable and will be applied to similar reactions to investigate other electrophiles on the reagent. Based on the activation parameters determined, this approach also gives insight into the mechanistic details of the trifluoromethylation and shows that these commonly known mechanisms mark the limits within which the reaction proceeds.
- Published
- 2015
48. The Screening Compound Collection: A Key Asset for Drug Discovery
- Author
-
Thierry Kimmerlin, Thomas Sander, Julien Hazemann, Modest von Korff, Romain Siegrist, Christoph Boss, Oliver Peter, and Urs Lüthi
- Subjects
0301 basic medicine ,Screening compound selection process ,Knowledge management ,Computer science ,media_common.quotation_subject ,Drug Evaluation, Preclinical ,Asset (computer security) ,Screening compound collection ,Small Molecule Libraries ,03 medical and health sciences ,Drug Discovery ,Quality (business) ,QD1-999 ,media_common ,Virtual tnt-library ,business.industry ,Drug discovery ,Compound library committee (clc) ,General Medicine ,General Chemistry ,Chemical space ,High-Throughput Screening Assays ,Chemistry ,030104 developmental biology ,Key (cryptography) ,business ,Algorithms - Abstract
In this case study on an essential instrument of modern drug discovery, we summarize our successful efforts in the last four years toward enhancing the Actelion screening compound collection. A key organizational step was the establishment of the Compound Library Committee (CLC) in September 2013. This cross-functional team consisting of computational scientists, medicinal chemists and a biologist was endowed with a significant annual budget for regular new compound purchases. Based on an initial library analysis performed in 2013, the CLC developed a New Library Strategy. The established continuous library turn-over mode, and the screening library size of 300'000 compounds were maintained, while the structural library quality was increased. This was achieved by shifting the selection criteria from 'druglike' to 'leadlike' structures, enriching for non-flat structures, aiming for compound novelty, and increasing the ratio of higher cost 'Premium Compounds'. Novel chemical space was gained by adding natural compounds, macrocycles, designed and focused libraries to the collection, and through mutual exchanges of proprietary compounds with agrochemical companies. A comparative analysis in 2016 provided evidence for the positive impact of these measures. Screening the improved library has provided several highly promising hits, including a macrocyclic compound, that are currently followed up in different Hit-to-Lead and Lead Optimization programs. It is important to state that the goal of the CLC was not to achieve higher HTS hit rates, but to increase the chances of identified hits to serve as the basis of successful early drug discovery programs. The experience gathered so far legitimates the New Library Strategy.
- Published
- 2017
49. Improved Gamma-Heating Calculational Methods for Fast Reactors and Their Validation for Plutonium-Burning Configurations
- Author
-
G. Rimpault, Rakesh Chawla, Anton Lüthi, Swiss Federal Institute of Technology (SFIT), Institut de Géologie, CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
- Subjects
Materials science ,[PHYS.NUCL]Physics [physics]/Nuclear Theory [nucl-th] ,Fission ,Nuclear engineering ,0211 other engineering and technologies ,chemistry.chemical_element ,Combustion ,Reflector (antenna) ,02 engineering and technology ,Blanket ,[PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex] ,01 natural sciences ,law.invention ,Nuclear physics ,Heating ,law ,Dosimetry ,0103 physical sciences ,021108 energy ,Eranos ,Burnup ,Platinum ,010308 nuclear & particles physics ,Gamma rays ,Gamma ray ,Nuclear reactor ,Plutonium ,Fast reactors ,Nuclear Energy and Engineering ,chemistry ,Steel ,Fission reactions - Abstract
International audience; A new calculational scheme has been developed for the accurate assessment of gamma heatingin fast reactors, its special feature being the determination of the gamma source distribution that isformulated in a near-to-exact manner. The improved methodology, which has been implemented into theERANOS (European Reactor Analysis Optimized System) code package, is currently validated for Puburningconfigurations, for which gamma-heating target accuracies are particularly high. This has beenaccomplished through comparisons with new integral measurements conducted at the MASURCA facility,as well as with reevaluated earlier experiments. In the new measurements, absolute gamma-heating rateswere determined in PuO2/UO2–fueled cores surrounded by a steel/sodium reflector, mainly using TLD-700 thermoluminescent dosimeters. Thereby, a considerable effort was undertaken to minimize systematicerrors. The calculation/experiment values determined from the analysis of the critical experiments are0.90 for the PuO2/UO2 core region, 0.84 for the steel/sodium reflector, and 0.89 for an internal steel/sodium diluent zone. The most plausible causes for the observed discrepancies have been identified to bedata related, i.e., too low fission gamma energies and too low capture cross sections for the structuralelements. The transferability of the current validation findings to a modified Superphénix configuration, inwhich the radial fertile blanket is replaced by a steel/sodium reflector, and to the 1500 MW(electric)Pu-burning CAPRA 4/94 reference design has been demonstrated.
- Published
- 2017
50. Editorial
- Author
-
Hans Peter Lüthi
- Subjects
Chemistry ,QD1-999 - Published
- 2017
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