Synthesis of N-heterocyclic carbene gold(I) complexes : towards the development of new organometallic drugs

Les applications biomédicales des complexes d'or à base de carbènes N-hétérocycliques (NHC) commencent à se développer. Certains complexes NHCs d'or(I) cationiques montrent une activité antimitochondriale, un mode d'action très prometteur dans la lutte contre le cancer; grâce à leur charge positive ces complexes ciblent préférentiellement les cellules tumorales, conduisant à la mort cellulaire. Dans ces travaux de thèse, trois familles de nouveaux complexes d'or à ligands NHCs et montrant un potentiel intéressant dans le domaine de la recherche biomédicale ont été synthétisés et caractérisés. Le premier groupe est formé par trois composés hétérobimétalliques luminescents or(I)-ruthenium(II) contenant des ligands hétéroditopiques de type bipyridine-NHC. Ces composés ont été étudiés biologiquement par des tests in vitro pour leurs activités antitumorale, antileishmaniale et antipaludique. Enfin, des études d'imagerie par microscopie confocale dans les cellules cancéreuses ont été réalisées en exploitant les propriétés de luminescence de ces composés. Le deuxième groupe est constitué par des complexes d'or(I) contenant deux ligands 1-[2 (diéthylamino)éthyle]imidazolydène. Tout d'abord, ces complexes ont été testés pour leur activité antiproliférative sur une lignée cellulaire du cancer de la prostate PC-3. La lipophilie (Log P) des composés a été déterminée. Le complexe le plus actif a été testé pour son activité cytotoxique sur cinq lignées de cellules tumorales humaines et des cellules endothéliales primaires. Le complexe le plus actif démontré une sélectivité pour les cellules cancéreuses. En outre, les activités anti-leishmaniose et antipaludique des composés ont été étudiées montrant des résultats intéressants. Le troisième groupe concerne un composé hétéro-dinucléaire d'or(I)-argent(I) et un complexe hétéro-trinucléaire or(I)-cuivre(II) contenant des ligands phénantroline-NHC. Ces composés sont formés par deux unités organométalliques différentes, pour une application potentielle en anticancer.Biomedical applications of gold complexes based on N-heterocyclic carbenes (NHCs) are beginning to unfold. Some cationic gold(I) NHCs complexes show antimitochondrial activities, a very promising action mode in the fight against cancer; due to their positive charge these complexes target preferentially tumor cells, leading to cell death. In this work of thesis, three groups of new NHC-based gold and heterobimetallic complexes involving aliphatic or aromatic amino-functionalized NHCs with interesting potential in biomedical research have been synthesized and characterized. The first group is formed by three luminescent heterobimetallic gold(I)-ruthenium(II) complexes containing heteroditopic bipyridine-NHC ligands. These compounds have been biologically investigated by in vitro tests for their antitumoral, antileishmanial and antimalarial activities. Finally, imaging studies in cancer cells have been performed exploiting the luminescent properties of the most active compound. The second group of molecules is concerned by cationic gold(I) complexes containing two 1-[2-(diethylamino)ethyl]imidazolydene ligands. First the complexes have been tested for their antiproliferative activity in prostate cancer cell line PC-3. Lipophilicity (Log P) has been determined for these complexes. The most active complex has been tested for the cytotoxic activities in five human cancer cell lines and primary endothelial cells demonstrating a potent action and selectivity for cancer cells. In addition, antileishmanial and antimalarial activities of these compounds have been investigated showing interesting results. The third group is formed by a hetero-dinuclear gold(I)-silver(I) and a trinuclear gold(I)-copper(II) complexes containing phenanthroline-NHC ligands. The compounds are formed by two different organometallic units potentially able to act as multi-targeting anticancer drug

Minimum Quench Energy and Early Quench Development in NbTi Superconducting Strands

The stability of superconducting wires is a crucial task in the design of safe and reliable superconducting magnets. These magnets are prone to premature quenches due to local releases of energy. In order to simulate these energy disturbances, various heater technologies have been developed, such as coated tips, graphite pastes, and inductive coils. The experiments studied in the present work have been performed using a single-mode diode laser with an optical fiber to illuminate the superconducting strand surface. Minimum quench energies and voltage traces at different magnetic flux densities and transport currents have been measured on an LHC-type, Cu/NbTi wire bathed in pool boiling helium I. This paper deals with the numerical analysis of the experimental data. In particular, a coupled electromagnetic and thermal model has been developed to study quench development and propagation, focusing on the influence of heat exchange with liquid helium

Pedunculated Angiomyofibroblastoma of the Vulva: Case Report and Review of the Literature

Angiomyofibroblastoma (AMFB) is a rare benign mesenchymal tumour that occurs almost exclusively in the vulvovaginal region of women but can also occur occasionally in the inguinoscrotal region of men. It is a well-circumscribed lesion that clinically is often thought to represent a Bartholin's gland cyst and usually does not form a pedunculated mass. To our knowledge, only five cases of vulvar AMFB with pedunculated mass have been reported in the English literature and all cases involving the labia majora and middle-aged women. We report the first case of pedunculated AMFB of the vulva occurring in a young woman of 21 years old and involving the left labia minora. After excluding the most common diseases, pedunculated AMFB should be part of differential diagnosis in the workup of any pedunculated vulvar mass even in young women with a lesion involving the labia minora. We reviewed the literature and summarized all reported cases

The GALEX Ultraviolet Virgo Cluster Survey (GUViCS) III. The Ultraviolet Source Catalogs

In this paper we introduce the deepest and most extensive ultraviolet extragalactic source catalogs of the Virgo Cluster area to date. Archival and targeted GALEX imaging is compiled and combined to provide the deepest possible coverage over ~120 deg^2 in the NUV (lambda_eff=2316 angstroms) and ~40 deg^2 in the FUV (lambda_eff=1539 angstroms) between 180 deg <= R.A. <= 195 deg and 0 deg <= Decl. <= 20 deg. We measure the integrated photometry of 1770 extended UV sources of all galaxy types and use GALEX pipeline photometry for 1,230,855 point-like sources in the foreground, within, and behind the cluster. Extended source magnitudes are reliable to m_UV ~22, showing ~0.01 sigma difference from their asymptotic magnitudes. Point-like source magnitudes have a 1 sigma standard deviation within ~0.2 mag down to m_uv ~23. The point-like source catalog is cross-matched with large optical databases and surveys including the SDSS DR9 (> 1 million Virgo Cluster sources), the Next Generation Virgo Cluster Survey (NGVS; >13 million Virgo Cluster sources), and the NED (~30,000 sources in the Virgo Cluster). We find 69% of the entire UV point-like source catalog has a unique optical counterpart, 11% of which are stars and 129 are Virgo cluster members neither in the VCC nor part of the bright CGCG galaxy catalog (i.e., m_pg < 14.5). These data are collected in four catalogs containing the UV extended sources, the UV point-like sources, and two catalogs each containing the most relevant optical parameters of UV-optically matched point-like sources for further studies from SDSS and NGVS. The GUViCS catalogs provide a unique set of data for future works on UV and multiwavelength studies in the cluster and background environments.Comment: 35 pages, 24 figures, 15 tables, Accepted for publication in A&

Graphene Nanoflake Uptake Mediated by Scavenger Receptors

The biological interactions of graphene have been extensively investigated over the last 10 years. However, very little is known about graphene interactions with the cell surface and how the graphene internalization process is driven and mediated by specific recognition sites at the interface with the cell. In this work, we propose a methodology to investigate direct molecular correlations between the biomolecular corona of graphene and specific cell receptors, showing that key protein recognition motifs, presented on the nanomaterial surface, can engage selectively with specific cell receptors. We consider the case of apolipoprotein A-I, found to be very abundant in the graphene protein corona, and observe that the uptake of graphene nanoflakes is somewhat increased in cells with greatly elevated expression of scavenger receptors B1, suggesting a possible mechanism of endogenous interaction. The uptake results, obtained by flow cytometry, have been confirmed using Raman microspectroscopic mapping, exploiting the strong Raman signature of graphene

A Novel Insulin/Glucose Model after a Mixed-Meal Test in Patients with Type 1 Diabetes on Insulin Pump Therapy

Current closed-loop insulin delivery methods stem from sophisticated models of the glucose-insulin (G/I) system, mostly based on complex studies employing glucose tracer technology. We tested the performance of a new minimal model (GLUKINSLOOP 2.0) of the G/I system to characterize the glucose and insulin dynamics during multiple mixed meal tests (MMT) of different sizes in patients with type 1 diabetes (T1D) on insulin pump therapy (continuous subcutaneous insulin infusion, CSII). The GLUKINSLOOP 2.0 identified the G/I system, provided a close fit of the G/I time-courses and showed acceptable reproducibility of the G/I system parameters in repeated studies of identical and double-sized MMTs. This model can provide a fairly good and reproducible description of the G/I system in T1D patients on CSII, and it may be applied to create a bank of "virtual" patients. Our results might be relevant at improving the architecture of upcoming closed-loop CSII systems

A microfluidic approach for synthesis and kinetic profiling of branched gold nanostructures

Automatized approaches for nanoparticle synthesis and characterization represent a great asset to their applicability in the biomedical field by improving reproducibility and standardization, which help to meet the selection criteria of regulatory authorities. The scaled-up production of nanoparticles with carefully defined characteristics, including intrinsic morphological features, and minimal intra-batch, batch-to-batch, and operator variability, is an urgent requirement to elevate nanotechnology towards more trustable biological and technological applications. In this work, microfluidic approaches were employed to achieve fast mixing and good reproducibility in synthesizing a variety of gold nanostructures. The microfluidic setup allowed exploiting spatial resolution to investigate the growth evolution of the complex nanoarchitectures. By physically isolating intermediate reaction fractions, we performed an advanced characterization of the shape properties during their growth, not possible with routine characterization methods. Employing an in-house developed method to assign a specific identity to shapes, we followed the particle growth/deformation process and identified key reaction parameters for more precise control of the generated morphologies. Besides, this investigation led to the optimization of a one-pot multi-size and multi-shape synthesis of a variety of gold nanoparticles. In summary, we describe an optimized platform for highly controlled synthesis and a novel approach for the mechanistic study of shape-evolving nanomaterials

Gas-Bearing Early-Type Dwarf Galaxies in Virgo: Evidence for Recent Accretion

We investigate the dwarf (M_B> -16) galaxies in the Virgo cluster in the radio, optical, and ultraviolet regimes. Of the 365 galaxies in this sample, 80 have been detected in HI by the Arecibo Legacy Fast ALFA survey. These detections include 12 early-type dwarfs which have HI and stellar masses similar to the cluster dwarf irregulars and BCDs. In this sample of 12, half have star-formation properties similar to late type dwarfs, while the other half are quiescent like typical early-type dwarfs. We also discuss three possible mechanisms for their evolution: that they are infalling field galaxies that have been or are currently being evolved by the cluster, that they are stripped objects whose gas is recycled, and that the observed HI has been recently reaccreted. Evolution by the cluster adequately explains the star-forming half of the sample, but the quiescent class of early-type dwarfs is most consistent with having recently reaccreted their gas.Comment: 18 pages, 9 figure

A modular phage vector platform for targeted photodynamic therapy of Gram-negative bacterial pathogens

: Growing antibiotic resistance has encouraged the revival of phage-inspired antimicrobial approaches. On the other hand, photodynamic therapy (PDT) is considered a very promising research domain for the protection against infectious diseases. Yet, very few efforts have been made to combine the advantages of both approaches in a modular, retargetable platform. Here, we foster the M13 bacteriophage as a multifunctional scaffold, enabling the selective photodynamic killing of bacteria. We took advantage of the well-defined molecular biology of M13 to functionalize its capsid with hundreds of photo-activable Rose Bengal sensitizers and contemporarily target this light-triggerable nanobot to specific bacterial species by phage display of peptide targeting moieties fused to the minor coat protein pIII of the phage. Upon light irradiation of the specimen, the targeted killing of diverse Gram(-) pathogens occurred at subnanomolar concentrations of the phage vector. Our findings contribute to the development of antimicrobials based on targeted and triggerable phage-based nanobiotherapeutics

FAST–ASKAP Synergy: Quantifying Coexistent Tidal and Ram Pressure Strippings in the NGC 4636 Group

Combining new HI data from a synergetic survey of ASKAP WALLABY and FAST with the ALFALFA data, we study the effect of ram pressure and tidal interactions in the NGC 4636 group. We develop two parameters to quantify and disentangle these two effects on gas stripping in HI-bearing galaxies: the strength of external forces at the optical-disk edge, and the outside-in extents of HI-disk stripping. We find that gas stripping is widespread in this group, affecting 80% of HI-detected non-merging galaxies, and that 41% are experiencing both types of stripping. Among the galaxies experiencing both effects, the two types of strengths are independent, while two HI-stripping extents moderately anticorrelate with each other. Both strengths are correlated with HI-disk shrinkage. The tidal strength is related to a rather uniform reddening of low-mass galaxies (M