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TBRT allows the control of cyclisation within branched polymer architectures by simply changing dilution. Increased cyclisation leads to changes in physical properties, therefore, tunig of behaviour is available without changing starting materials.

Building a document-level classifier for COVID-19 on radiology reports could help assist providers in their daily clinical routine, as well as create large numbers of labels for computer vision models. We have developed such a classifier by fine-tuning a BERT-like model initialized from RadBERT, its continuous pre-training on radiology reports that can be used on all radiology-related tasks. RadBERT outperforms all biomedical pre-trainings on this COVID-19 task (P0.01) and helps our fine-tuned model achieve an 88.9 macro-averaged F1-score, when evaluated on both X-ray and CT reports. To build this model, we rely on a multi-institutional dataset re-sampled and enriched with concurrent lung diseases, helping the model to resist to distribution shifts. In addition, we explore a variety of fine-tuning and hyperparameter optimization techniques that accelerate fine-tuning convergence, stabilize performance, and improve accuracy, especially when data or computational resources are limited. Finally, we provide a set of visualization tools and explainability methods to better understand the performance of the model, and support its practical use in the clinical setting. Our approach offers a ready-to-use COVID-19 classifier and can be applied similarly to other radiology report classification tasks.

This contribution attempts to show that a small number of toponyms in Jura continues Latin derivatives in -ĀNU (most often inflected in the plural) based on nomina gentilicia in -ius. The use of this technique of formation has never been reported in this department. The author suggests that this characteristic Latin model of naming fundi spread in the southern part of the city of Sequanes from the Rhodanian Narbonensis, under the influence of Vienne. Its use denotes foundations and eponymous families who played a pioneering role in the process of romanization.

PDF file - 140K, Vessel stabilization

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PDF file - 139, ER� is efficiently suppressed in BM and BM-derived cells using chimeric hematopoietic approach

PDF file - 364K, B16K1, LL2 and 4T1 characterization

PDF file - 162K, Vessel diameter quantification by granulometry

PDF file - 122K, B16K1 time- and size-dependent tumor harvesting

Estrogens directly promote the growth of breast cancers that express the estrogen receptor α (ERα). However, the contribution of stromal expression of ERα in the tumor microenvironment to the protumoral effects of estrogen has never been explored. In this study, we evaluated the molecular and cellular mechanisms by which 17β-estradiol (E2) impacts the microenvironment and modulates tumor development of ERα-negative tumors. Using different mouse models of ER-negative cancer cells grafted subcutaneously into syngeneic ovariectomized immunocompetent mice, we found that E2 potentiates tumor growth, increases intratumoral vessel density, and modifies tumor vasculature into a more regularly organized structure, thereby improving vessel stabilization to prevent tumor hypoxia and necrosis. These E2-induced effects were completely abrogated in ERα-deficient mice, showing a critical role of host ERα. Notably, E2 did not accelerate tumor growth when ERα was deficient in Tie2-positive cells, even in mice grafted with wild-type bone marrow. These results were extended by clinical evidence of ERα-positive stromal cell labeling in the microenvironment of human breast cancers. Together, our findings therefore show that E2 promotes the growth of ERα-negative cancer cells through the activation of stromal ERα (extra-hematopoietic Tie-2 positive cells), which normalizes tumor angiogenesis and allows an adaptation of blood supply to tumors, thereby preventing hypoxia and necrosis. These findings significantly deepen mechanistic insights into the impact of E2 on tumor development with potential consequences for cancer treatment. Cancer Res; 72(12); 3010–9. ©2012 AACR.

PDF file - 204K, B16K1 Tumor necrosis in C57BL/6 mice

Three new synthesis strategies for branched statistical copolymers containing analogues of step-growth backbones are shown using free radical chemistries and transfer-dominated branching radical polymerisation (TBRT) conditions.

Transfer-dominated Branching Radical Telomerisation (TBRT) enables the production of branched polymers with step-growth backbones using radical telomerisation chemistry. By conducting identical TBRTs over a broad temperature range, the role of temperature in telomer formation and branching has been evaluated. Elevated temperature limits telomer length, thereby allowing a10% reduction in the amount of telogen required to produce near identical high molecular weight branched polymers.

The transcriptional repressions driven by the circadian core clock repressors RevErbα, E4BP4, and CRY1/PER1 involve feedback loops which are mandatory for generating the circadian rhythms. These repressors are known to bind to cognate DNA binding sites, but how their circadian bindings trigger the cascade of events leading to these repressions remain to be elucidated. Through molecular and genetic analyses, we now demonstrate that the chromatin protein HP1α plays a key role in these transcriptional repressions of both the circadian clock (CC) genes and their cognate output genes (CCGs). We show that these CC repressors recruit the HP1α protein downstream from a repressive cascade, and that this recruitment is mandatory for the maintenance of both the CC integrity and the expression of the circadian genes. We further show that the presence of HP1α is critical for both the repressor-induced chromatin compaction and the generation of “transcriptionally repressed biomolecular hydrophobic condensates” and demonstrates that HP1α is mandatory within the CC output genes for both the recruitment of DNA methylating enzymes on the intronic deoxyCpG islands and their subsequent methylation.

We demonstrate that there is a tight functional relationship between two highly evolutionary conserved cell processes, i.e., the circadian clock (CC) and the circadian DNA demethylation–methylation of cognate deoxyCpG-rich islands. We have discovered that every circadian clock-controlled output gene (CCG), but not the core clock nor its immediate-output genes, contains a single cognate intronic deoxyCpG-rich island, the demethylation–methylation of which is controlled by the CC. During the transcriptional activation period, these intronic islands are demethylated and, upon dimerization of two YY1 protein binding sites located upstream to the transcriptional enhancer and downstream from the deoxyCpG-rich island, store activating components initially assembled on a cognate active enhancer (a RORE, a D-box or an E-box), in keeping with the generation of a transcriptionally active condensate that boosts the initiation of transcription of their cognate pre-mRNAs. We report how these single intronic deoxyCpG-rich islands are instrumental in such a circadian activation/repression transcriptional process.

The comparison of the lexical data gathered by the LEI and the medieval and contemporary anthroponymic data gathered by PatRom makes it possible to measure, on a concrete example (the delexical personal names formed on continuators of regional Proto-Romance */karne-lakˈsare/ ‘Shrove Tuesday’), the contributions, modest but not negligible, of anthroponymy to historical lexicology.

La copie du cartulaire de Sauxillanges conservée aux Archives Nationales (LL. 1014), copie exécutée au xviiie siècle, contient aux folios 6 verso à 8 recto (« fol. 4 de l’orig. »), sous le numéro 6, un bref de cens acéphale concernant la localité de Plauzat (Puy-de-Dôme). Partiellement rédigé en langue d’oc, ce document n’a pas été édité par Doniol (1864), qui s’est basé sur la seule copie du cartulaire (xviie siècle) conservée à la Bibliothèque Nationale, et il ne semble pas avoir été signal...

Le document dont on trouvera ci-dessous l’édition accompagnée de commentaires est l’un des plus anciens brefs de cens qui aient été repérés dans la partie septentrionale de l’Auvergne. Souvent rédigés partiellement voire entièrement en langue d’oc, les documents de ce type, consistant essentiellement en des listes nominales, ont joué dans l’Auvergne du xie siècle un rôle important dans l’émergence de l’occitan à la scripturalité. C’est surtout de ce point de vue qu’on étudiera ce nouveau cens...

Amine functionality offers the modification of polymer properties to enable stimuli-responsive behaviour, and this feature has been utilised in numerous studies of self-assembly and disassembly. The ability to place amines as pendant groups along linear polymer backbones within distinct blocks, at chain ends or as statistical mixtures with other functionalities, has allowed fine tuning of responses to pH. Here we study and compare the placement of amines within the backbones or as pendant groups within polyesters synthesised by the newly reported transfer-dominated branching radical telomerisation (TBRT). Branched polymers with backbone amines are clearly shown to undergo dissolution that is determined by pH and telogen selection; they undergo nanoprecipitation only when hydrophilic telogens are present within their structure and provide nanoprecipitates that are highly sensitive to the addition of acid. In contrast, TBRT polymers with pendant amines form uniform nanoparticles with remarkable stability to pH changes, under identical nanoprecipitation conditions. The behaviour differences shown here open new avenues of synthetic flexibility for pH-responsive polymer design using TBRT.

New branched polymerisations offer previously inaccessible macromolecules and architectural understanding is important as it provides insight into the branching mechanism and enables the determination of structure–property relationships. Here we present a detailed inverse gated 13C NMR characterisation of materials derived from the very recently reported Transfer-dominated Branching Radical Telomerisation (TBRT) approach to quantify branching and provide an insight into cyclisation.

For almost a century, vitamin A has been known as a nutrient critical for normal development, differentiation, and homeostasis; accordingly, there has been much interest in understanding its mechanism of action. This review is about the discovery of specific receptors for the vitamin A derivative, retinoic acid (RA), which launched extensive molecular, genetic, and structural investigations into these new members of the nuclear receptor superfamily of transcriptional regulators. These included two families of receptors, the RAR isotypes (α, β, and γ) along with three RXR isotypes (α, β, and γ), which bind as RXR/RAR heterodimers to cis-acting response elements of RA target genes to generate a high degree of complexity. Such studies have provided deep molecular insight into how the widespread pleiotropic effects of RA can be generated.

Thiol-functionalized block copolymer vesicles are readily prepared via RAFT-mediated polymerization-induced self-assembly (PISA). More specifically, a disulfide-functionalized poly(glycerol monomethacrylate) macro-CTA is chain-extended using 2-hydroxypropyl methacrylate): the growing water-insoluble poly(2-hydroxypropyl methacrylate) chains drive in situ self-assembly to produce diblock copolymer vesicles in concentrated aqueous solution. The disulfide bonds in the poly(glycerol monomethacrylate) stabilizer chains are reductively cleaved in situ using either tributyl phosphine or tris(2-carboxyethyl)phosphine to generate thiol groups, which react immediately with either a quaternary acrylate to introduce cationic character or with rhodamine B acrylate or rhodamine B isothiocyanate to confer a convenient fluorescent tag. In addition to such facile derivatization, such thiol-functionalized vesicles may offer some potential for drug delivery applications, because enhanced muco-adhesion is anticipated for these nano-objects.

The commercial synthesis of polymers is generally limited to two main mechanisms that are typically considered to be mutually exclusive, namely step-growth and chain-growth polymerisation. This also defines the vast number of academic advances in macromolecular synthesis including the increasingly studied reversible deactivation radical polymerisation techniques (chain-growth) and complex polymer architectures such as dendrimers (step-growth). We report here a new synthetic strategy that utilises conventional free radical chain-growth chemistry, under modified telomerisation conditions, to form branched polymers containing chemistries conventionally formed under step-growth conditions. Telomerisation is typically limited to small molecule synthesis and employs addition across the unsaturated bond of a substrate, whilst minimising intermolecular reaction between substrates. Through the careful manipulation of reaction conditions, we have created a ‘transfer dominated branching radical telomerisation’ mechanism that creates branched polymers containing step-growth motifs from multi-vinyl monomers, with molecular weights in excess of 1000 kg mol−1, using industrially relevant free radical chain-growth chemistry. The scope of this approach is considerable, allowing access to entirely new macromolecular structures.

Boudou assista, au cours des festivites de la Sainte-Estelle de 1950, a la presentation par Mouly, d’un rapport sur l’enseignement de la langue d’oc a l’ecole primaire. Il redige, le 4 juin, une lettre au Majoral suivie d’un Ensaj d’unificacion grafica. Toutes deux inedites, cette lettre et cette etude permettent d’apprehender la position qui etait celle de l’auteur de la Santa Estela dans le debat orthographique, vers 1950. Il nous a donc semble utile de publier ces documents qui marquent une etape dans l’itineraire orthographique de Boudou, mais qui eclairent aussi, pensons-nous, certains aspects de sa personnalite et de sa posture litteraires. L’edition de la lettre et celle de l’Ensaj sont suivies d’un glossaire.

Complex macromolecular architectures offer innovation opportunities through the formation of new polymers with novel physical and chemical behaviour. Optimally existing commercial feedstocks are used as the introduction of new small molecule chemistries may extend regulatory requirements at high expense. In a highly orthogonal synthesis strategy, we recently utilised telomerisation approaches, conventionally targeting small molecule dimerisation, to generate high molecular weight branched polymers. Transfer-dominated Branching Radical Telomerisation (TBRT) employs radical reactions, but yields branched polymers with extended backbones resembling those conventionally formed via step-growth polymerisation. Here we examine the impact of taxogen dimensions on the outcomes of TBRT using multi-vinyl taxogens ethylene glycol dimethacrylate (EGDMA), 1,6-hexanediol dimethacrylate (HDMA) and 1,12-dodecanediol dimethacrylate (LDMA). Marked differences in gelation behaviours were correlated to the dimensions of the taxogen, notably due to the shifting balance of intermolecular and intramolecular branching processes occuring during TBRT.

Thanks to Burgundy’s toponymy we are able to postulate the existence of about ten complex lexical units (unattested in the dictionaries) formed on poirier and denoting different types of pear tree.

OBJECTIVE: Retinoid X receptors (RXR) are a family of nuclear receptors that play critical roles in the regulation of numerous fundamental biological processes including cell proliferation, differentiation, and death. Earlier studies suggested that treatment with RXR agonists attenuates platelet activation in all adults (male and femal) and mice; however, the underlying molecular mechanisms have remained insufficiently understood. To elaborate further on this issue, we characterized megakaryocyte and platelet-specific RXR knockout mice to study platelet function in vitro and arterial thrombosis in vivo. APPROACH AND RESULTS: First, we identified RXRbeta as the dominant RXR receptor in mouse platelets, prompting us to generate a megakaryocyte and platelet-specific PF4(Cre) ;RXRbeta(flox/flox) mouse. Second, we studied activation, spreading, and aggregation of platelets from C57Bl/6 wild-type mice (WT), PF4(Cre+) ;RXRbeta(flox/flox) mice, and PF4(Cre-) ;RXRbeta(flox/flox) littermate controls in the presence or absence of RXR ligands, that is, 9-cis-retinoic acid (9cRA) and methoprene acid (MA). We found that in vitro treatment with RXR ligands attenuates spreading and aggregation of platelets and increases proplatelet particle formation from megakaryocytes (MK). However, these effects are also observed in RXRbeta-deficient platelets and MKs and are thus independent of RXRbeta. Third, we investigated arterial thrombus formation in an iron chloride (FeCl3)-induced vascular injury model in vivo, which is also not affected by the absence of RXRbeta in platelets. CONCLUSIONS: Absence of the most abundant RXR receptor in mouse platelets, RXRbeta, does not affect platelet function in vitro and thrombus formation in vivo. Furthermore, RXR agonists' mediated effects on platelet function are independent of RXRbeta expression. Hence, our data do not support a significant contribution of RXRbeta to arterial thrombosis in mice.

Seventy years after the discovery of their anti-inflammatory properties, glucocorticoids (GCs) remain the mainstay treatment for major allergic and inflammatory disorders, such as atopic dermatitis, asthma, rheumatoid arthritis, colitis, and conjunctivitis, among others. However, their long-term therapeutical administration is limited by major debilitating side effects, e.g., skin atrophy, osteoporosis, Addison-like adrenal insufficiency, fatty liver, and type 2 diabetes syndrome, as well as growth inhibition in children. These undesirable side effects are mostly related to GC-induced activation of both the direct transactivation and the direct transrepression functions of the GC receptor (GR), whereas the activation of its GC-induced indirect tethered transrepression function results in beneficial anti-inflammatory effects. We have reported in the accompanying paper that the nonsteroidal compound CpdX as well as its deuterated form CpdX-D3 selectively activate the GR indirect transrepression function and are as effective as synthetic GCs at repressing inflammations generated in several mouse models of major pathologies. We now demonstrate that these CpdX compounds are bona fide selective GC receptor agonistic modulators (SEGRAMs) as none of the known GC-induced debilitating side effects were observed in the mouse upon 3-mo CpdX treatments. We notably report that, unlike that of GCs, the administration of CpdX to ovariectomized (OVX) mice does not induce a fatty liver nor type 2 diabetes, which indicates that CpdX could be used in postmenopausal women as an efficient "harmless" GC substitute.

On se propose de montrer que le troubadour rouergat Daude de Prades (…1208-ca 1243) est l’auteur de deux des trois coblas que la tradition manuscrite designe comme les plus appreciees : Dos gratz conquer hom ab un do (PC 461, 98) et la cobla dobla D’home fol e desconoissen (PC 461, 86). Repris tous les deux dans le Breviari d’Amor, ces poemes moralisants ont pour matrice deux passages qui se succedent (v. 372-392 et 393-407) dans le traite de Daude de Prades sur les Quatre Vertus cardinales (une traduction enormement amplifiee de Martin de Braga). Chemin faisant, on discute la datation des deux coblas, que l’on propose de situer entre 1220 et ca 1243. Il se confirme ainsi qu’apres son entree dans le chapitre cathedral de Rodez en 1214, Daude de Prades n’a pas abandonne completement l’ecriture de pieces lyriques. Son succes dans l’art de la forme breve est l’un des elements qui conduisent a reconsiderer la place qui lui est jusqu’ici concedee dans la litterature romane medievale.

Gouiran (2006) a consacre a la celebre aube anonyme En un vergier sotz fuella d’albespi un commentaire precis et convaincant. Nos remarques s’attachent surtout a tirer certaines consequences de ce commentaire quant au fonctionnement et a la portee du texte. Au vers V, 1, le poeme commande l’inversion de son interpretation et exige une lecture retroactive inscrivant les strophes I-IV dans le monde onirique : nul amant n’a passe la nuit aupres de la reveuse. Ayant d’abord donne tous les gages de son appartenance generique, le texte recuse retroactivement la situation de base du genre : la separation des amants a l’aube. L’inversion fournit le principe unificateur qui organise le poeme : inversion de la lecture, inversion des univers de reference, inversion de la convention generique et, bien sur, inversion du sexe de l’actant principal (une femme). En un vergier apparait alors comme un texte d’une haute (meta)litterarite : un jeu sur les codes et le sens, et avec l’auditeur/lecteur.

The purpose of this contribution is to give an etymology to two Occitan words regarded as of unknown origin by the FEW. Velay prounseau ‘a kind of thrush’ is a regular issue of Old Occitan proensal ‘of Provence’. The nasalized form prounsean is a phono-stylistic and zoolectal variant of prounseau.

It is well-known that the Dengue fever virus undergoes a distinct morphological transition from topologically smooth particles to ‘bumpy’ particle on increasing the temperature from that of the mosquito carrier (28 °C) to that of the human host (37 °C). This virus also possesses pH-sensitive surface domains that undergo conformational changes during infection which facilitates exit from the endosomes. Herein we take a bio-inspired approach to design synthetic Dengue virus-mimicking nanoparticles to target triple-negative (TN) breast cancer cells that overexpress SR-B1 scavenger receptors. Thus, sterile pH-responsive methacrylic ABC triblock copolymer vesicles were prepared in aqueous solution via polymerization-induced self-assembly. Microphase separation between two enthalpically-incompatible hydrophobic membrane-forming blocks produced a well-defined framboidal morphology, with surface globules of ∼28 nm diameter protruding from the membrane. The hydrophilic stabilizer block comprises 97% hydroxyl-functionalized chains and 3% phosphorylcholine-functionalized chains, with the latter being critical for selective intracellular uptake. These framboidal vesicles remain intact at neutral pH but become swollen and cationic at pH 5–6 because the tertiary amine residues in the hydrophobic C block become protonated. We demonstrate that such nanoparticles enable selective targeting of TN breast cancer cells. This is because such malignant cells overexpress SR-B1 receptors for naturally-occurring phospholipids and hence take up the phosphorylcholine-decorated framboidal vesicles preferentially. In contrast, negligible cell uptake is observed over the same time period for both human dermal fibroblasts and normal breast cancer cells that minimally express the SR-B1 receptor. Moreover, we show that genetic material within such pH-responsive framboidal vesicles can be efficiently delivered to the cell nuclei while maintaining high cell viability.

According to the Vita S. Illidii written at the beginning of the twelfth century, when Saint Alyre Abbey was really flourishing, the vicus six miles from Clermont in Auvergne where Alyre was born was called Alleriacus. Although tradition places it near Dallet, on the banks of the Allier, its exact location and identification remained thus far unclear. The diplomatic documentation (end eleventh-fourteenth centuries), however, allows us to identify it with a villa turned domain, Aleyrat, of which the memory is still preserved today in the form of Leyras, on the left bank of the Allier, opposite Dallet.

Cu-Catalysed reversible-deactivation radical polymerisation of hydrophobic methacrylate monomers in anhydrous alcohols has been expanded to explore the scope of this unusual choice of solvent. A range of linear methacrylic homopolymers with well-targeted molecular weight and low dispersity (Đ = 1.12–1.53) have been generated in anhydrous methanol and isopropanol with relative ease. These solvents are normally considered antisolvents and employed to precipitate such polymers; therefore, our studies have assessed the polymerisation reaction mixture homogeneity and extent of reaction control. Statistical copolymerisations with the bi-functional monomer, ethylene glycol di-methacrlylate (EGDMA), has led to branched statistical copolymers with weight average molecular weights up to Mw = 1.76 × 106 g mol−1; subsequent triple-detection size exclusion chromatography studies have provided insight into the impact of monomer structure on the extent of branching within the final isolated polymers. The ability to control branched copolymer molecular weights under these conditions through variation of EGDMA concentrations was seen to be highly dependent on methacrylate monomer chemistry. A number of factors which are likely to effect branching reactions during the polymerisation of hydrophobic methacrylates in anhydrous alcohols are discussed.

Le present article s’applique a etablir le sens du vers 4 d’Ab la douzor del temps novel, le celebre poeme de Guillaume de Poitiers. On procede en premier lieu a la critique des interpretations precedentes (en particulier a celle des plus recentes : Pasero, Vallin, Gambino). Ces interpretations ont en commun l’idee que, dans le passage a l’examen, le mot vers ne possede pas son sens technique ordinaire (“composition poetique versifiee, accompagnee d’une melodie”). A cette affirmation indemontree, qui conduit, soit a corriger arbitrairement le texte, soit a imaginer, pour rendre compte d’une seule occurrence du mot, des sens de vers qui s’averent non attestes par ailleurs (“melodie” ou “cri d’un animal”), on oppose le principe lexicographique de Mohren : « Un sens insolite est un sens errone ». Sur la base de ce principe, on soutient ensuite que le vers en discussion et tout le debut du poeme admettent sans difficulte une lecture respectueuse de la valeur lexicale accoutumee de vers.