Bone Marrow Stromal Cells Drive Key Hallmarks of B Cell Malignancies.

All B cell leukaemias and a substantial fraction of lymphomas display a natural niche residency in the bone marrow. While the bone marrow compartment may only be one of several sites of disease manifestations, the strong clinical significance of minimal residual disease (MRD) in the bone marrow strongly suggests that privileged niches exist in this anatomical site favouring central elements of malignant transformation. Here, the co-existence of two hierarchical systems, originating from haematopoietic and mesenchymal stem cells, has extensively been characterised with regard to regulation of the former (blood production) by the latter. How these two systems cooperate under pathological conditions is far less understood and is the focus of many current investigations. More recent single-cell sequencing techniques have now identified an unappreciated cellular heterogeneity of the bone marrow microenvironment. How each of these cell subtypes interact with each other and regulate normal and malignant haematopoiesis remains to be investigated. Here we review the evidences of how bone marrow stroma cells and malignant B cells reciprocally interact. Evidently from published data, these cell-cell interactions induce profound changes in signalling, gene expression and metabolic adaptations. While the past research has largely focussed on understanding changes imposed by stroma- on tumour cells, it is now clear that tumour-cell contact also has fundamental ramifications for the biology of stroma cells. Their careful characterisations are not only interesting from a scientific biological viewpoint but also relevant to clinical practice: Since tumour cells heavily depend on stroma cells for cell survival, proliferation and dissemination, interference with bone marrow stroma-tumour interactions bear therapeutic potential. The molecular characterisation of tumour-stroma interactions can identify new vulnerabilities, which could be therapeutically exploited

Reactivity of Triphenyl Phosphorothionate in Lubricant Oil Solution

Investigating the thermo-oxidative reactivity of anti-wear additives in lubricant oil solution at high temperature can significantly contribute to an understanding of the mechanism of thermal film and tribofilm formation on metal surfaces. In this study, the reactivity of triphenyl phosphorothionate (TPPT) in lubricant oil solution at high temperature (423 and 473K) has been studied by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy. The results show that the TPPT molecule was highly thermally stable and did not completely decompose in oil solution even upon heating at 423K for 168h and at 473K for 72h. The degradation of the TPPT molecule, which turned out to be a first-order reaction, started taking place after 6h at both temperatures, leading to the breakage of the P=S bond with the formation of triphenyl phosphate. During these heating experiments, no oil-insoluble compounds were detected. The oxidation of the base oil as a result of the prolonged heating demonstrated that the TPPT molecule did not effectively act as oxidation inhibito

Fusion of satellite images of different spatial resolutions: Assessing the quality of resulting images

International audienceMethods have been proposed to produce multispectral images with enhanced spatial resolution using one or more images of the same scene of better spatial resolution. Assuming that the main concern of the user is the quality of the transformation of the multispectral content when increasing the spatial resolution, this paper defines the properties of such enhanced multispectral images. It then proposes both a formal approach and some criteria to provide a quantitative assessment of the spectral quality of these products. Five sets of criteria are defined. They measure the performance of a method to synthesize the radiometry in a single spectral band as well as the multispectral information when increasing the spatial resolution. The influence of the type of landscape present in the scene upon the assessment of the quality is underlined, as well as its dependence with scale. The whole approach is illustrated by the case of a SPOT image and three different standard methods to enhance the spatial resolutio

In Situ Attenuated Total Reflection (ATR/FT-IR) Tribometry: A Powerful Tool for Investigating Tribochemistry at the Lubricant-Substrate Interface

To investigate the chemical changes occurring at metal/lubricant interfaces under tribological conditions in the boundary-lubrication regime, an in situ system for conducting quantitative tribological measurements has been constructed by combining an attenuated total reflection Fourier-transform infrared (ATR/FT-IR) spectrometer with a reciprocating tribometer. By periodically acquiring ATR/FT-IR spectra during sliding, spectroscopic changes due to thermal and/or tribochemical reactions occurring at the metal/oil interface can be monitored and correlated with friction measurements. The usefulness of this tribological test system has been demonstrated by performing ATR tribological experiments in the presence of a poly-α-olefin base oil at high temperature (423K) on iron-coated germanium ATR crystal

Substituent Effect on the Reactivity of Alkylated Triphenyl Phosphorothionates in Oil Solution in the Presence of Iron Particles

The effect of the substituent attached to the phenyl rings on the reactivity of alkylated triphenyl phosphorothionates (t-butyl TPPT (b-TPPT) and p-nonyl TPPT (n-TPPT)) in oil solution at high temperature (423 and 473K) was investigated by means of Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) spectroscopy and X-ray photoelectron spectroscopy (XPS). The FT-IR and NMR results show that the alkylated TPPTs were highly thermally stable and did not completely decompose in oil, even upon heating at 423K for 168h and at 473K for 72h, with and without steel filings and iron particles (both metallic iron and iron oxide particles). The reaction of alkylated TPPTs was found to start with the scission of the P=S bond to yield alkylated triphenyl phosphate. The kinetics of the thermo-oxidative reaction was slower when steel filings and iron particles were added to the oil solutions during the heating experiments. The reactivity of the unsubstituted molecule (TPPT) was higher than that of alkylated TPPTs at 423K, while at 473K TPPT and n-TPPT were more reactive than b-TPPT. In the case of the experiments performed at 473K in the presence of steel filings or metallic iron or iron oxide particles, the reactivity of the alkylated TPPT molecules decreased with the length of the alkyl chain bound to the phenyl rings. The XPS results show that a reaction layer consisting of carbon, oxygen, phosphorus and iron was formed on the 100Cr6 steel filings immersed for 72h in oil solutions containing alkylated TPPTs and heated at 473K. Sulphur was neither detected on the surface nor in the composition vs depth profile. During the heating experiments, the base oil (PAO) was oxidized. At 423K, the alkylated TPPTs had a strong antioxidant effect, which was found to be more pronounced upon increasing the length of the alkyl chain bound to the phenyl rings. At 473K, the TPPTs did not inhibit the oxidation of the base oil as effectively as at 423

Il ponte e lo specchio

Starting point of the article’s thesis is the author's personal experience of theatrical practice and contact with other theatrical cultures, especially in Asia and, even more, in Japan. Aim of the text is to analyse the reasons for the mutual fascination between typically Western theatrical forms and practices, such as what is generically defined as Commedia dell'Arte and others that, equally generically, are defined as Oriental Theatres. This attraction has origins (even if subconscious) that are not only theatrical but rather cultural, or even better, related to cultural visions. The image of the Commedia dell’Arte - a tradition re-invented in the course of the 20th century and made mythical in the collective imagination by the theatrical avant-gardes in the perspective of a profound renewal of European theatre - corresponds to a vision of a generic Theatre of the East, repository of a sort of imaginary purity that has remained uncontaminated and unchanged over the centuries - the so-called living traditions. These theatrical visions are, in turn, the result of the construction of induced cultural identities, of distorted visions of the Other. They are thus part of a cultural imagology that rests on the sedimentation of ideological constructs ranging from mythopoiesis to exoticism, and even corresponds to an induced vision of identity of Japan and Italy. Finally, by returning the discussion to a purely artistic sphere, the importance of the dynamics leading to the hybridisation of languages is assessed, a fertile ground for the connection and construction of cultural bridges and a heuristic practice, moreover, typical of the Commedia dell'Arte, as it made hybridisation its essence, modulating and regenerating itself in European theatres, and not only, from the 16th century onwards.L’articolo prende spunto dall’esperienza personale della pratica teatrale e del contatto dell’autore con altre culture teatrali, in particolare dell’Asia e ancor più in particolare del Giappone, per analizzare le ragioni della reciproca fascinazione e attrazione fra forme teatrali e pratiche tipicamente occidentali quali quella che si definisce genericamente come Commedia dell’Arte e quelle, altrettanto genericamente, definite con la formula di Teatri orientali. Le ragioni di questa attrazione hanno spesso, seppure inconsciamente, origini non solo puramente teatrali, ma piuttosto culturali o, meglio ancora, di visioni culturali. All’immagine della Commedia dell’Arte, una tradizione re-inventata nel corso del XX secolo e resa mitica nell’immaginario collettivo dalle avanguardie teatrali nell’ottica di un profondo rinnovamento del teatro europeo, corrisponde una visione di un generico “teatro dell’Oriente” depositario di una sorta di purezza immaginaria non contaminata e rimasta inalterata nel corso dei secoli, le cosiddette tradizioni viventi. Queste visioni teatrali sono, a loro volta, frutto della costruzione di identità culturali indotte, di visioni distorte dell’Altro, entrando quindi nel dominio di una imagologia culturale che poggia sulla sedimentazione di costrutti ideologici che spaziano dalla mitopoiesi all’esotismo fino a corrispondere addirittura con una visione identitaria, indotta, del Giappone e dell’Italia. Riportando il discorso in un ambito prettamente artistico, si valuta infine l’importanza delle dinamiche che portano all’ibridazione dei linguaggi, terreno fertile per la connessione e la costruzione di ponti culturali e pratica euristica, peraltro, propria alla Commedia dell’Arte che fece dell’ibridazione la sua essenza modulandosi e rigenerandosi nei teatri europei, e non solo, dal ‘500 ad oggi

Oncogenic Signalling in t(12;21) Acute Lymphoblastic Leukaemia

The t(12;21)(p13;q22) translocation is present in up to 25% of children with pre-B cell Acute Lymphoblastic Leukaemia (ALL). This translocation involves two transcription factors, TEL (ETV6) and AML (RUNX1), both of which have crucial roles in regulating haematopoiesis. Clinically, TEL-AML1 positive patients have good prognoses. However, late relapses, additional genetic lesions affecting prognosis, and long-term side-effects of chemotherapy remain a cause for concern. In light of recent studies showing genetic and functional heterogeneities in cells responsible for cancer clone maintenance and propagation, targeting common deregulated pathways may be critical for the success of novel therapies. Using Affymetrix GeneChip global gene expression analysis our laboratory previously identified three genes: Tbx2, E2f5 and Lif-R, specifically expressed in TEL-AML1 transduced mouse foetal liver haematopoietic progenitor cells (HPC) cells compared with control cells. Over-expression of these genes was confirmed by real-time qPCR and the specificity of target gene expression was evaluated in human TEL-AML1 positive and negative leukaemia cells. Pathway analysis of TEL-AML1 transcriptional target genes also demonstrated deregulated expression of genes associated with STAT3 signalling, known to be one of the most important pathways required for proliferation and maintenance of multipotency in cancer stem cells. In this study we demonstrate the importance of STAT3 activity in a mouse model of TEL-AML1 overexpression, in human TEL-AML1 positive leukaemia cells and primary human leukaemic samples. Our data indicate a central role for TEL-AML1 in maintaining activated STAT3. This is mediated by transcriptional induction of the Guanine nucleotide exchange factor, ARHGEF4, leading to RAC1 activation and consequent stimulation of STAT3. The latter is necessary for survival, proliferation and self-renewal of TEL-AML1 positive leukaemia through transcriptional induction of MYC expression. In conclusion, we show a novel signalling pathway important for maintenance of t(12;21) leukaemia that constitutes a promising novel therapeutic target for the treatment of this disease

Chain-length-identification strategy in zinc polyphosphate glasses by means of XPS and ToF-SIMS

The surface chemistry of amorphous zinc polyphosphates of different compositions (ranging from zinc metaphosphate to zinc orthophosphate) has been investigated by means of X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary-ion mass spectroscopy (ToF-SIMS). The identification of the chain length of zinc polyphosphates by XPS was on the basis of the integrated intensity ratio of the bridging (P-O-P) and nonbridging (P = O and P-O-M) oxygen peaks used for fitting the oxygen 1s signal, the shift of the P 2p3/2 signal towards lower binding energies and the modified Auger parameter towards higher values as the zinc content increases. The discrimination of the polyphosphate chain lengths was also achieved by ToF-SIMS, by comparing the intensities of selected characteristic phosphate fragments. Both techniques appear to be suitable for the investigation of polyphosphate glasses in applications such as tribology, where there is a need to identify the chain length present in the outermost monolayer of the film. Fourier-transform infrared (FT-IR) spectroscopy was used to characterize the bulk compounds. The FT-IR studies showed that long-chain structures linked through P-O-P bonds predominate in the metaphosphate composition, while when the zinc content is increased, the chains become shorter, ultimately being replaced by PO4 monomers in the orthophosphate composition. Figure

Thermal Properties of the Binary-Filler Composites with Few-Layer Graphene and Copper Nanoparticles

The thermal properties of an epoxy-based binary composites comprised of graphene and copper nanoparticles are reported. It is found that the "synergistic" filler effect, revealed as a strong enhancement of the thermal conductivity of composites with the size-dissimilar fillers, has a well-defined filler loading threshold. The thermal conductivity of composites with a moderate graphene concentration of ~15 wt% exhibits an abrupt increase as the loading of copper nanoparticles approaches ~40 wt%, followed by saturation. The effect is attributed to intercalation of spherical copper nanoparticles between the large graphene flakes, resulting in formation of the highly thermally conductive percolation network. In contrast, in composites with a high graphene concentration, ~40 wt%, the thermal conductivity increases linearly with addition of copper nanoparticles. The electrical percolation is observed at low graphene loading, less than 7 wt.%, owing to the large aspect ratio of graphene. At all concentrations of the fillers, below and above the electrical percolation threshold, the thermal transport is dominated by phonons. The obtained results shed light on the interaction between graphene fillers and copper nanoparticles in the composites and demonstrate potential of such hybrid epoxy composites for practical applications in thermal interface materials and adhesives.Comment: 25 pages, 4 figure

Tribochemistry of Bulk Zinc Metaphosphate Glasses

Zinc polyphosphate glasses are the principal component of the antiwear tribofilms formed on steel surfaces in the presence of additives, such as zinc dialkyldithiophosphates. In this work, amorphous, zinc metaphosphate glasses have been synthesized and characterized by means of X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), elemental analysis, and X-ray photoelectron spectroscopy (XPS). Tribological tests were performed by rubbing steel balls against the zinc metaphosphate discs in a poly-α-olefin (PAO) bath at room temperature. XPS was used in order to characterize the tribostressed areas on both metaphosphate discs and steel balls. A transfer film, constituted of iron and zinc polyphosphates, was formed on the contact area of the balls. This transfer film was found to reduce friction and prevent ball wear. A reduction in the relative intensities of XPS signals related to bridging-oxygen species and a binding energy shift of 0.4eV of the P 2p toward lower values demonstrated the presence of shorter-chain-length phosphates inside the tribo-tracks on the discs. Furthermore, iron was transferred to the glass during the tribological tests. A tribochemical reaction between zinc metaphosphate and iron oxide has been proposed as an explanation for the depolymerization of the glass and the formation of iron phosphat