Publications associées à Effective Inhibition of TDP-43 Aggregation by Native State Stabilization

Targeting TDP-43 Proteinopathies in Neurodegeneration by its Native-State Stabilization

Preventing the misfolding or aggregation of TDP-43 is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In our work, we provide proof of concept that native state stabili ...

EPFL2024

Drug Screening in C. elegans to identify new pharmacological mitochondrial stress inducers

Amélia Lalou

Mitochondria are essential organelles participating in numerous cellular functions, including energy harvesting, regulation of homeostasis and apoptosis. Changes in mitochondrial number, morphology, and function not only impact cellular metabolism but also ...

EPFL2024

From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

Mahdi Hijazi

The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

EPFL2024

Course Design - A Visual and Modular Approach

Marc Laperrouza

This book has been designed for instructors in higher education or adult training who wish to develop a new course or revise an existing one. It adopts a practical, visual, and modular approach based on the principle of constructive alignment. At its heart ...

EPFL Press2024

Teaching Not To

Charlotte Malterre-Barthes

Two design studios were successively taught in two schools of architecture: one at the Harvard Graduate School of Design (GSD) and the other at the Swiss Federal Institute of Technology in Lausanne (EPFL) in Lausanne, Switzerland, based on "A Global Morato ...

Taylor & Francis Inc2024

Method of preparation of amyloidogenic protein aggregates and uses thereof

Hilal Lashuel, Galina Limorenko

The invention relates to methods for the preparation of method of preparation of Tau aggregates, including fibrils, fibrillar species, soluble and insoluble oligomeric species, new Tau aggregates and uses thereof. The invention further relates to the uses ...

2024

Cyclic Peptides for Drug Development

Christian Heinis, Xinjian Ji, Alexander Lund Nielsen

Cyclic peptides are fascinating molecules abundantly found in nature and exploited as molecular format for drug development as well as other applications, ranging from research tools to food additives. Advances in peptide technologies made over many years ...

Wiley-VCH Verlag GmbH2024

Methods for high-throughput synthesis and screening of peptide libraries

Zsolt Bognár

Macrocycles provide an attractive modality for drug development but the identification of ligands to targets of interest is hindered by the lack of large macrocyclic compound libraries for high-throughput screening. A strategy to efficiently synthesize lar ...

EPFL2024

Analytical Computation of the Sensitivity Coefficients in Hybrid AC/DC Networks

Mario Paolone, Willem Lambrichts

In this paper, we present a model for the analytical computation of the power flow sensitivity coefficients (SCs) for hybrid AC/DC networks. The SCs are defined as the partial derivates of the nodal voltages with respect to the active and reactive power in ...

2024

SC-TPTP: An Extension of the TPTP Derivation Format for Sequent-Based Calculus

Simon Guilloud

Motivated by the transfer of proofs between proof systems, and in particular from first order automated theorem provers (ATPs) to interactive theorem provers (ITPs), we specify an extension of the TPTP derivation text format to describe proofs in first-ord ...

2024

Orthologic with Axioms

Viktor Kuncak, Simon Guilloud

We study the proof theory and algorithms for orthologic, a logical system based on ortholattices, which have shown practical relevance in simplification and normalization of verification conditions. Ortholattices weaken Boolean algebras while having polyno ...

Association for Computing Machinery2024

The predictive capacity of in vitro preclinical models to evaluate drugs for the treatment of retinoblastoma

Paul Joseph Dyson, Irina Sinenko, Roland Christopher Turnell-Ritson

Retinoblastoma is a rare childhood cancer of the eye. Of the small number of drugs are used to treat retinoblastoma, all have been repurposed from drugs developed for other conditions. In order to find drugs or drug combinations better suited to the improv ...

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD2023

Recombinant Full-Length TDP-43 Oligomers Retain Their Ability to Bind RNAs, Are Not Toxic, and Do Not Seed TDP-43 Aggregation in Vitro

Hilal Lashuel, Lixin Yang, Yllza Jasiqi

TAR DNA-binding protein with 43 kD (TDP-43) is a partially disordered protein that misfolds and accumulates in the brains of patients affected by several neurodegenerative diseases. TDP-43 oligomers have been reported to form due to aberrant misfolding or ...

Amer Chemical Soc2023

Deconstructing and Reconstructing the Complexity of Tau pathology

Galina Limorenko

This thesis consists of four Chapters unified by a singular theme â how do we develop disease models that faithfully reproduce the pathology seen in patients suffering from neurodegenerative disorders associated with the Tau protein, such as Alzheimerâ ...

EPFL2023

LISA – A Modern Proof System

Viktor Kuncak, Simon Guilloud, Sankalp Gambhir

We present LISA, a proof system and proof assistant for constructing proofs in schematic first-order logic and axiomatic set theory. The logical kernel of the system is a proof checker for first-order logic with equality and schematic predicate and fun ...

Dagstuhl, Germany, Schloss Dagstuhl - Leibniz-Zentrum fur Informatik2023

Discontinuous Galerkin methods for Fisher-Kolmogorov equation with application to a-synuclein spreading in Parkinson's disease

Alfio Quarteroni, Francesca Bonizzoni

This spreading of prion proteins is at the basis of brain neurodegeneration. This paper deals with the numerical modelling of the misfolding process of a-synuclein in Parkinson's disease. We introduce and analyse a discontinuous Galerkin method for the sem ...

Elsevier Science Sa2023

A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers

Camila Bacellar Cases Da Silveira, Christoph Bostedt

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we ...

Nature Portfolio2023

Computational Conceptual Design – Typological Exploration Of Spatial Truss Systems Through Optimization

Corentin Jean Dominique Fivet, Jonas Warmuth, Pierluigi D'Acunto

Exploring a wide range of relevant design options from the outset is crucial for every sound conceptual design process. Optimization techniques are generally employed to generate well-performing structural design options. However, focusing only on performa ...

2023

Nanomole-scale photochemical thiol-ene chemistry for high-throughput late-stage diversification of peptide macrocycles

Mischa Schüttel, Alexander Lund Nielsen, Mark Daniel Nolan

The photochemical thiol-ene reaction is an efficient method for rapid and chemoselective formation of thioether linkages under mild conditions. It has found widespread use in small-molecule synthesis as well as peptide and protein chemistry. While high-thr ...

WILEY2023

Optimised three-dimensional in vitro retinoblastoma models tailored for drug discovery and clinical translatability

Irina Sinenko

Retinoblastoma, while relatively rare, stands as the most prevalent intraocular cancer. In Switzerland, the survival rate approaches 100%, but it drops to less than 50% in low-income countries. The current treatment options for retinoblastoma rely on a lim ...

EPFL2023