The computation of the geoid model in the state of São Paulo using two methodologies and GOCE models

The purpose of this manuscript is to compute and to evaluate the geoid model in the State of São Paulo from two methodologies (Stokes' integral through the Fast Fourier Transform - FFT and Least Squares Collocation - LSC). Another objective of this study is to verify the potentiality of GOCE-based. A special attention is given to GOCE mission. The theory related to Stokes' integral and Least Squares Collocation is also discussed in this work. The spectral decomposition was employed in the geoid models computation and the long wavelength component was represented by EGM2008 up to degree and order 150 and 360 and GOCE-based models up to 150. The models were compared in terms of geoid height residual and absolute and relative comparisons from GPS/leveling and the results show consistency between them. In addition, a comparison in the mountain regions was carried out to verify the methodologies behavior in this area; the results showed that LSC is less consistent than FFT

Mechanism of the gas phase reactions of the C5H5Ni+ and C5H5Co+ ions with substituted pyridines. A combined experimental and theoretical study

Different products have been observed in the reactions ofC5H5Co+ andC5H5Ni+ ions with halogen-substituted pyridines (XPy) that have been studied by ion trap mass spectrometry (ITMS) techniques.In particular,an addition product C5H5M(XPy)+and a product ion C5H4M(Py)+ corresponding to a loss of a HX molecule(X =F,Cl,Br)havebeen detected. Acomputational study at the DFT level on model-systems formed by 2-fluoro and 2-bromopyridine reacting either with the C5H5Ni+ or the C5H5Co+ ion has been carried out. This study shows the existence of a general mechanistic pattern. The rate-determining step of this mechanism is the migration of the halogen from the pyridine ring to the metal. A final hydrogen abstraction step carried out by the halogen leads to the expulsion of a HX molecule

A Theoretical Investigation on the Oxidation States of Palladium Complexes and their Role in Carbonylation Reaction

International audienceTwo different yet related topics are discussed: (i) the reduction of palladium (II) in Pd(OAc)2 complexes reacting with phenyl phosphines and leading to Pd(0) phosphines complexes and (ii) the carbonylation reaction of allyl chlorides catalyzed by these Pd(0) species. The results show that the overall reduction is an exothermic process that can be accomplished along two different reaction paths: one of them is clearly favoured. Similarly, three different channels have been determined for the carbonylation reaction that primarily differ for the timing and the way with which the reacting species bind the metal. In the first path (σ-path), the allyl fragment interacts very weakly with the metal, whereas, successively the CO molecule strongly binds it and reacts with the allyl. A second channel (π-η3 pathway) is characterized by a π-η3 interaction between the allyl fragment and the palladium, to which the CO molecule binds, before the two units react affording the product. In both cases, two consecutive migrations of the chlorine "assist" the course of the reaction. In a third case (η2 pathway) the allyl fragment initially enters the palladium coordination sphere, then the CO molecule simultaneously binds it and the phosphorous atom of one phosphine ligand. The first two paths are favoure

Mechanistic Insights into Enantioselective Gold-Catalyzed Allylation of Indoles with Alcohols: The Counterion Effect

Enantioselective gold-catalysis is emerging as a powerful tool in organic synthesis for the stereoselective manipulation of unfunctionalized unsaturated hydrocarbons. Despite the exponential growth, the molecular complexity of common chiral gold complexes generally prevents a complete description of the mechanism steps and activation modes being documented. In this study, we present the results of a combined experimental-computational (DFT) investigation of the mechanism of the enantioselective gold-catalyzed allylic alkylation of indoles with alcohols. A stepwise SN2′-process (i.e. antiauroindolination of the olefin, proton-transfer, and subsequent anti-elimination [Au]−OH) is disclosed, leading to a library of tricyclic-fused indole derivatives. The pivotal role played by the gold counterion, in terms of molecular arrangement (i.e. \u201cfolding ef fect\u201d) and proton-shuttling in restoring the catalytic species, is finally documente

Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant.

Heterogeneity of cancer-associated fibroblasts (CAFs) can result from activation of distinct signaling pathways. We show that in primary human dermal fibroblasts (HDFs), fibroblast growth factor (FGF) and transforming growth factor β (TGF-β) signaling oppositely modulate multiple CAF effector genes. Genetic abrogation or pharmacological inhibition of either pathway results in induction of genes responsive to the other, with the ETV1 transcription factor mediating the FGF effects. Duality of FGF/TGF-β signaling and differential ETV1 expression occur in multiple CAF strains and fibroblasts of desmoplastic versus non-desmoplastic skin squamous cell carcinomas (SCCs). Functionally, HDFs with opposite TGF-β versus FGF modulation converge on promoting cancer cell proliferation. However, HDFs with increased TGF-β signaling enhance invasive properties and epithelial-mesenchymal transition (EMT) of SCC cells, whereas HDFs with increased FGF signaling promote macrophage infiltration. The findings point to a duality of FGF versus TGF-β signaling in distinct CAF populations that promote cancer development through modulation of different processes

CSL controls telomere maintenance and genome stability in human dermal fibroblasts.

Genomic instability is a hallmark of cancer. Whether it also occurs in Cancer Associated Fibroblasts (CAFs) remains to be carefully investigated. Loss of CSL/RBP-Jκ, the effector of canonical NOTCH signaling with intrinsic transcription repressive function, causes conversion of dermal fibroblasts into CAFs. Here, we find that CSL down-modulation triggers DNA damage, telomere loss and chromosome end fusions that also occur in skin Squamous Cell Carcinoma (SCC)-associated CAFs, in which CSL is decreased. Separately from its role in transcription, we show that CSL is part of a multiprotein telomere protective complex, binding directly and with high affinity to telomeric DNA as well as to UPF1 and Ku70/Ku80 proteins and being required for their telomere association. Taken together, the findings point to a central role of CSL in telomere homeostasis with important implications for genomic instability of cancer stromal cells and beyond

Androgen receptor functions as transcriptional repressor of cancer-associated fibroblast activation.

The aging-associated increase of cancer risk is linked with stromal fibroblast senescence and concomitant cancer-associated fibroblast (CAF) activation. Surprisingly little is known about the role of androgen receptor (AR) signaling in this context. We have found downmodulated AR expression in dermal fibroblasts underlying premalignant skin cancer lesions (actinic keratoses and dysplastic nevi) as well as in CAFs from the 3 major skin cancer types, squamous cell carcinomas (SCCs), basal cell carcinomas, and melanomas. Functionally, decreased AR expression in primary human dermal fibroblasts (HDFs) from multiple individuals induced early steps of CAF activation, and in an orthotopic skin cancer model, AR loss in HDFs enhanced tumorigenicity of SCC and melanoma cells. Forming a complex, AR converged with CSL/RBP-Jκ in transcriptional repression of key CAF effector genes. AR and CSL were positive determinants of each other's expression, with BET inhibitors, which counteract the effects of decreased CSL, restoring AR expression and activity in CAFs. Increased AR expression in these cells overcame the consequences of CSL loss and was by itself sufficient to block the growth and tumor-enhancing effects of CAFs on neighboring cancer cells. As such, the findings establish AR as a target for stroma-focused cancer chemoprevention and treatment