Discriminative variable selection for clustering with the sparse Fisher-EM algorithm

The interest in variable selection for clustering has increased recently due to the growing need in clustering high-dimensional data. Variable selection allows in particular to ease both the clustering and the interpretation of the results. Existing approaches have demonstrated the importance of variable selection for clustering but turn out to be either very time consuming or not sparse enough in high-dimensional spaces. This work proposes to perform a selection of the discriminative variables by introducing sparsity in the loading matrix of the Fisher-EM algorithm. This clustering method has been recently proposed for the simultaneous visualization and clustering of high-dimensional data. It is based on a latent mixture model which fits the data into a low-dimensional discriminative subspace. Three different approaches are proposed in this work to introduce sparsity in the orientation matrix of the discriminative subspace through \(\ell _{1}\) -type penalizations. Experimental comparisons with existing approaches on simulated and real-world data sets demonstrate the interest of the proposed methodology. An application to the segmentation of hyperspectral images of the planet Mars is also presented.     

Degradable Hybrid Materials Based on Cationic Acylhydrazone Dynamic Covalent Polymers Promote DNA Complexation through Multivalent Interactions

The design of smart nonviral vectors for gene delivery is of prime importance for the successful implementation of gene therapies. In particular, degradable analogues of macromolecules represent promising targets as they would combine the multivalent presentation of multiple binding units that is necessary for achieving effective complexation of therapeutic oligonucleotides with the controlled degradation of the vector that would in turn trigger drug release. Toward this end, we have designed and synthesized hybrid polyacylhydrazone‐based dynamic materials that combine bis‐functionalized cationic monomers with ethylene oxide containing monomers. Polymer formation was characterized by ¹H and DOSY NMR spectroscopy and was found to take place at high concentration, whereas macrocycles were predominantly formed at low concentration. HPLC monitoring of solutions of these materials in aqueous buffers at pH values ranging from 5.0 to 7.0 revealed their acid‐catalyzed degradation. An ethidium bromide displacement assay and gel electrophoresis clearly demonstrated that, despite being dynamic, these materials are capable of effectively complexing dsDNA in aqueous buffer and biological serum at N/P ratios comparable to polyethyleneimine polymers. The self‐assembly of dynamic covalent polymers through the incorporation of a reversible covalent bond within their main chain is therefore a promising strategy for generating degradable materials that are capable of establishing multivalent interactions and effectively complexing dsDNA in biological media.     

Encapsulating Hydrides and Main-Group Anions in d10-Metal Clusters Stabilized by 1,1-Dichalcogeno Ligands

Cu(I) and Ag(I) can form with 1,1-dithio(seleno) ligands various types of clusters, the framework of which being maintained by the metal–chalcogen bonds provided by the bridging ligands. The metal centers are generally tricoordinated and consequently possess an accepting orbital of valence s and/or p character. There is no formal metal–metal bonding, but only weak d¹⁰–d¹⁰ interactions which favor the overlap between the metal accepting orbitals. Their bonding combinations are generally suited for interacting with the occupied valence orbitals of an encapsulated anion. Thus, many of these clusters are able to encapsulate anions, a situation which tends to stabilize the whole structure through building of significant host–guest bonding. Not only is the anion encapsulation effect to stabilize the cluster cage, but it can also significantly modify its structure, or act as a template in the stabilization of species which would not exist as empty clusters. This paper reviews the synthesis, structure and bonding of all the known clusters of d¹⁰ metals decorated with 1,1-dichalchogeno ligands and containing entrapped atomic anions. Their structures are analyzed with respect to size and shape. The photoluminescence properties of some of them are discussed.     

A Collaborative Journey towards the Late-Stage Functionalization of Added-Value Chemicals Using Engineered Halogenases

In 2017, two companies, Novartis AG and Syngenta AG, joined forces with the group of Prof. Buller, head of the Competence Center for Biocatalysis (CCBIO), to tackle the challenge of enzymatic late-stage halogenation. This biocatalytic method was considered to provide a more sustainable approach to late-stage halogenation of complex molecules than traditional synthetic approaches. Using machine-learning guided protein engineering, α-ketoglutarate dependent halogenases were evolved into versatile catalysts capable of selectively chlorinating inactivated C−H bonds. Structurally diverse molecules, namely an analogue of martinelline as well as two members of the soraphen natural product family, were enzymatically chlorinated at two distinct positions in a regio- and stereoselective manner, thus demonstrating the synthetic usefulness of such a strategy. As part of our three-year collaboration, flavin-dependent halogenases were also studied.     

A new pH-switchable dimannosyl[c2]daisy chain molecular machine

The preparation of a dimannosyl[c2]daisy chain molecular machine containing an ammonium and a triazolium station is described. The both stretched and contracted states of the molecular machine can be obtained by variation of the pH, thus localizing the mannosyl stoppers closer or farther away.     

Fabrication of Environmentally Biodegradable Lignin Nanoparticles

We developed a method for the fabrication of novel biodegradable nanoparticles (NPs) from lignin which are apparently non‐toxic for microalgae and yeast. We compare two alternative methods for the synthesis of lignin NPs which result in particles of very different stability upon change of pH. The first method is based on precipitation of low‐sulfonated lignin from an ethylene glycol solution by using diluted acidic aqueous solutions, which yields lignin NPs that are stable over a wide range of pH. The second approach is based on the acidic precipitation of lignin from a high‐pH aqueous solution which produces NPs stable only at low pH. Our study reveals that lignin NPs from the ethylene glycol‐based precipitation contain densely packed lignin domains which explain the stability of the NPs even at high pH. We characterised the properties of the produced lignin NPs and determined their loading capacities with hydrophilic actives. The results suggest that these NPs are highly porous and consist of smaller lignin domains. Tests with microalgae like Chlamydomonas reinhardtii and yeast incubated in lignin NP dispersions indicated that these NPs lack measurable effect on the viability of these microorganisms. Such biodegradable and environmentally compatible NPs can find applications as drug delivery vehicles, stabilisers of cosmetic and pharmaceutical formulations, or in other areas where they may replace more expensive and potentially toxic nanomaterials.     

An endoglycosidase with alternative glycan specificity allows broadened glycoprotein remodelling

Protein endoglycosidases are useful for biocatalytic alteration of glycans on protein surfaces, but the currently limited selectivity of endoglycosidases has prevented effective manipulation of certain N-linked glycans widely found in nature. Here we reveal that a bacterial endoglycosidase from Streptococcus pyogenes , EndoS, is complementary to other known endoglycosidases (EndoA, EndoH) used for current protein remodeling. It allows processing of complex-type N-linked glycans +/- core fucosylation but does not process oligomannose- or hybrid-type glycans. This biocatalytic activity now addresses previously refractory antibody glycoforms.     

Efficient synthesis and host-guest properties of a new class of calix[6]azacryptands

Two members of a new class of calix[6]azacryptands, namely, calix[6]tampo and calix[6]tamb, have been synthesized through an efficient [1 + 1] macrocyclization reaction--reduction sequence. One of them has been obtained in a remarkably high overall yield from the known X(6)H(3)Me(3). In comparison to all the other calix[6]azacryptands, they possess unique conformational properties since they present a rigidified cone conformation with a partial filling of the cavity by the methoxy groups. In contrast to calix[6]tampo, the fully protonated derivative of calix[6]tamb behaves as a remarkable molecular receptor toward polar neutral guests. NMR studies have shown that the intracavity binding process is governed by a conformational flip of the aromatic walls of the calixarene core.     

Tedanolide C: a potent new 18-membered-ring cytotoxic macrolide isolated from the Papua New Guinea marine sponge Ircinia sp

Cytotoxicity-guided fractionation of the crude methanol extract of a marine sponge, Ircinia sp., yielded tedanolide C (1), a new 18-membered macrolide. The structure was solved by interpreting NMR and MS data, and the relative stereochemistry was determined from a combination of homo- and heteronuclear coupling constants in conjunction with molecular modeling. Compound 1 exhibited potent cytotoxicity against HCT-116 cells in vitro. Cell cycle analysis showed that treatment of cells with compound 1 arrested cells in the S-phase.     

Catalytic alkylation of benzylic C-H bonds with 1,3-dicarbonyl compounds utilizing oxygen as terminal oxidant

The oxidative alkylation of benzylic C-H bonds with 1,3-dicarbonyl compounds was developed using oxygen as the terminal oxidant in the presence of catalytic amounts of FeCl₂, CuCl and NHPI.