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•Pyrolysis of waste tires using supported metal catalysts was investigated.•(Pd, Ni or Co)/SiO2 favor the aromatization and cracking reactions at low temperature.•Pd/SiO2 catalyst ...promoted the reactions toward the formation of aromatic compounds.•(Ni or Co)/SiO2 catalysts drive mainly to alkenes formation in the pyro-oil.•(Pd, Ni or Co)/SiO2 catalysts leads to a pyro-oil enriched in valuable hydrocarbons.
Metal catalysts based on Ni, Co, and Pd supported on SiO2 were evaluated in the catalytic pyrolysis of waste tires using pyrolysis experiments coupled to gas chromatography/mass spectrometry (Py–GC/MS) and thermogravimetric analysis coupled with Fourier Transform Infrared spectrometer (TGA–FTIR) techniques. The effect of temperature and the nature of metals on the product distribution and reaction pathways was determined. Catalytic pyrolysis promoted aromatization and cracking reactions at particularly low temperatures ca. 350 °C, leading mainly to the formation of alkenes (isoprene), aromatic terpenes (p-cymene), aliphatic terpenes (d,l-limonene), and other aromatic compounds such as benzene, toluene, and xylenes (BTX). The Pd/SiO2 catalyst was the most selective toward aromatic compounds (around 40 %), owing to its well-known hydrogenation/dehydrogenation capacity, while CC bond cleavage reactions, leading to alkenes, were more favored on the Ni/SiO2 and Co/SiO2 catalysts. In all cases, high selectivity to limonene and isoprene was observed at low temperature. Above 400 °C, no significant differences in product distribution were observed between catalyzed and uncatalyzed pyrolysis. Herein, selectivity toward high-value hydrocarbons (i.e., d,l-limonene, isoprene, BTX, and p-cymene) during the catalytic pyrolysis of waste tires was tuned by the nature of the supported transition metals (i.e., Ni, Co, Pd) and the reaction temperature (e.g., <400 °C). The results demonstrate that the use of these catalysts is a promising strategy to valorize waste tires into high added-value products.
Dengue virus (DENV) is a mosquito-borne virus of the family
The RNA viral genome encodes three structural and seven nonstructural proteins. Nonstructural protein 1 (NS1) is a multifunctional protein ...actively secreted in vertebrate and mosquito cells during infection. In mosquito cells, NS1 is secreted in a caveolin-1-dependent manner by an unconventional route. The caveolin chaperone complex (CCC) is a cytoplasmic complex formed by caveolin-1 and the chaperones FKBP52, Cy40, and CyA and is responsible for the cholesterol traffic inside the cell. In this work, we demonstrate that in mosquito cells, but not in vertebrate cells, NS1 associates with and relies on the CCC for secretion. Treatment of mosquito cells with classic secretion inhibitors, such as brefeldin A, Golgicide A, and Fli-06, showed no effect on NS1 secretion but significant reductions in recombinant luciferase secretion and virion release. Silencing the expression of CAV-1 or FKBP52 with short interfering RNAs or the inhibition of CyA by cyclosporine resulted in significant decrease in NS1 secretion, again without affecting virion release. Colocalization, coimmunoprecipitation, and proximity ligation assays indicated that NS1 colocalizes and interacts with all proteins of the CCC. In addition, CAV-1 and FKBP52 expression was found augmented in DENV-infected cells. Results obtained with Zika virus-infected cells suggest that in mosquito cells, ZIKV NS1 follows the same secretory pathway as that observed for DENV NS1. These results uncover important differences in the dengue virus-cell interactions between the vertebrate host and the mosquito vector as well as novel functions for the chaperone caveolin complex.
The dengue virus protein NS1 is secreted efficiently from both infected vertebrate and mosquito cells. Previously, our group reported that NS1 secretion in mosquito cells follows an unconventional secretion pathway dependent on caveolin-1. In this work, we demonstrate that in mosquito cells, but not in vertebrate cells, NS1 secretion takes place in association with the chaperone caveolin complex, a complex formed by caveolin-1 and the chaperones FKBP52, CyA, and Cy40, which are in charge of cholesterol transport inside the cell. Results obtained with ZIKV-infected mosquito cells suggest that ZIKV NS1 is released following an unconventional secretory route in association with the chaperone caveolin complex. These results uncover important differences in the virus-cell interactions between the vertebrate host and the mosquito vector, as well as novel functions for the chaperone caveolin complex. Moreover, manipulation of the NS1 secretory route may prove a valuable strategy to combat these two mosquito-borne diseases.
The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures ...derived from publicly available data. We utilized three independent published studies to acquire or generate lists of differentially expressed genes between control and SARS-CoV-2-infected samples. Using a rank-based pattern matching strategy based on the Kolmogorov-Smirnov Statistic, the signatures were queried against drug profiles from Connectivity Map (CMap). We validated 16 of our top predicted hits in live SARS-CoV-2 antiviral assays in either Calu-3 or 293T-ACE2 cells. Validation experiments in human cell lines showed that 11 of the 16 compounds tested to date (including clofazimine, haloperidol and others) had measurable antiviral activity against SARS-CoV-2. These initial results are encouraging as we continue to work towards a further analysis of these predicted drugs as potential therapeutics for the treatment of COVID-19.
exon 14 splice site alterations that cause exon skipping at the mRNA level (
ex14) are actionable oncogenic drivers amenable to therapy with MET tyrosine kinase inhibitors (TKI); however, secondary ...resistance eventually arises in most cases while other tumors display primary resistance. Beyond relatively uncommon on-target MET kinase domain mutations, mechanisms underlying primary and acquired resistance remain unclear.
We examined clinical and genomic data from 113 patients with lung cancer with
ex14. MET TKI resistance due to
mutation was functionally evaluated using
and
models.
Five of 113 patients (4.4%) with
ex14 had concurrent
G12 mutations, a rate of
cooccurrence significantly higher than in other major driver-defined lung cancer subsets. In one patient, the
mutation was acquired post-crizotinib, while the remaining 4
ex14 patients harbored the
mutation prior to MET TKI therapy. Gene set enrichment analysis of transcriptomic data from lung cancers with
ex14 revealed preferential activation of the KRAS pathway. Moreover, expression of oncogenic KRAS enhanced MET expression. Using isogenic and patient-derived models, we show that
mutation results in constitutive activation of RAS/ERK signaling and resistance to MET inhibition. Dual inhibition of MET or EGFR/ERBB2 and MEK reduced growth of cell line and xenograft models.
mutation is a recurrent mechanism of primary and secondary resistance to MET TKIs in
ex14 lung cancers. Dual inhibition of MET or EGFR/ERBB2 and MEK may represent a potential therapeutic approach in this molecular cohort.
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•Catalytic transformation of cyclohexanone into secondary amines.•A reaction map for the catalytic amination of cyclohexanone is proposed.•A kinetic model describing the amination of ...cyclohexanone is elucidated.•The effect of temperature, reactant concentrations and H2-equivalents is assessed.
The liquid phase amination of the cyclohexanone (CyO) with aniline (PhNH2) was studied on a Pd/C catalyst using NaCO2H as a H-donor. Catalytic tests were performed in batch reactors by varying reactant concentrations (0, 0.1, 0.2 and 0.4 mol/L), the temperature (80–160 °C) and H2-equivalents availability (0, 2 and 4 H2-equivalents with respect to CyO). The results indicate that, the use of NaCO2H barely affect the reactivity (measured as initial reaction rate) while it does influence the selectivity to secondary amines. This effect was ascribed to the limited effectivity of the H2 transfer, which was controlled by the water formed after the condensation of the CyO with the PhNH2, hydrogen solubility in toluene, and the mass transfer from the liquid to the catalyst surface. The experimental observations were consistent with a multi-step mechanism consisting in: a first step of condensation of the ketone and the amine to form an imine, followed by the disproportionation of the imine into secondary amines. The kinetic measurements at initial rate conditions were well interpreted by a Langmuir Hinshelwood (L-H) kinetic model, which suggest that the surface reaction to form the intermediary imine is the rate limiting step (R.L.S).
The stress of the Golgi apparatus is an autoregulatory mechanism that is induced to compensate for greater demand in the Golgi functions. No examples of Golgi stress responses due to physiological ...stimuli are known. Furthermore, the impact on this organelle of viral infections that occupy the vesicular transport during replication is unknown. In this work, we evaluated if a Golgi stress response is triggered during dengue and Zika viruses replication, two flaviviruses whose replicative cycle is heavily involved with the Golgi complex, in vertebrate and mosquito cells. Using GM-130 as a Golgi marker, and treatment with monensin as a positive control for the induction of the Golgi stress response, a significant expansion of the Golgi cisternae was observed in BHK-21, Vero E6 and mosquito cells infected with either virus. Activation of the TFE3 pathway was observed in the infected cells as indicated by the translocation from the cytoplasm to the nucleus of TFE3 and increased expression of pathway targeted genes. Of note, no sign of activation of the stress response was observed in CRFK cells infected with Feline Calicivirus (FCV), a virus released by cell lysis, not requiring vesicular transport. Finally, dilatation of the Golgi complex and translocation of TFE3 was observed in vertebrate cells expressing dengue and Zika viruses NS1, but not NS3. These results indicated that infections by dengue and Zika viruses induce a Golgi stress response in vertebrate and mosquito cells due to the increased demand on the Golgi complex imposed by virion and NS1 processing and secretion.
There is a general lack of understanding on the detailed processes and mechanism of low-angle translational block slides. The September 20, 2018 Naga landslide, with a volume of 27 M m
3
and a runout ...distance of 1.34 km, provided new insights on the initiation, transport, and deposition mechanisms of this type of landslide. Drone photogrammetry, video footage, satellite images, slope stability analyses, and field evidence revealed that the landslide occurred as multiple block detachments along a series of tension cracks that formed and grew progressively prior to the main failure. Predominance of intact upright blocks traceable to the distal end of the deposit indicates dominant translational motion. Facies within the Naga landslide deposit revealed that at least three processes (slide, dry flow, and fall) occurred during the main movement. Post-slide processes immediately after emplacement included small avalanches and rockfalls related to the instability of the landslide deposit and the main scarp. Preliminary slope stability analyses showed that the slopes were marginally unstable (FoS 0.67–3.96) even in dry conditions. The low-angle profile of the slip surface (6°) favors stability, but low shear strength of the limestone bedrock and unsupported cut slopes may have contributed to the failure.
rearrangements are oncogenic drivers that are enriched in invasive mucinous adenocarcinomas (IMA) of the lung. The oncoprotein binds ERBB3-ERBB2 heterodimers and activates downstream signaling, ...supporting a therapeutic paradigm of ERBB3/ERBB2 inhibition. As proof of concept, a durable response was achieved with anti-ERBB3 mAb therapy (GSK2849330) in an exceptional responder with an
-rearranged IMA on a phase I trial (NCT01966445). In contrast, response was not achieved with anti-ERBB2 therapy (afatinib) in four patients with
-rearranged IMA (including the index patient post-GSK2849330). Although
data supported the use of either ERBB3 or ERBB2 inhibition, these clinical results were consistent with more profound antitumor activity and downstream signaling inhibition with anti-ERBB3 versus anti-ERBB2 therapy in an
-rearranged patient-derived xenograft model. Analysis of 8,984 and 17,485 tumors in The Cancer Genome Atlas and MSK-IMPACT datasets, respectively, identified
rearrangements with novel fusion partners in multiple histologies, including breast, head and neck, renal, lung, ovarian, pancreatic, prostate, and uterine cancers.
This series highlights the utility of ERBB3 inhibition as a novel treatment paradigm for
-rearranged cancers. In addition, it provides preliminary evidence that ERBB3 inhibition may be more optimal than ERBB2 inhibition. The identification of
rearrangements across various solid tumors supports a basket trial approach to drug development.
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•The Oxy-species in the carbon support leads to the oxidation of the Feº clusters.•Carbothermic reduction contributes to the regeneration of the Feº active sites.•The temperature for ...tar decomposition over Fe/CAG must be higher than 700 °C.
Iron-catalyzed tar decomposition is studied by inspecting changes in catalytic activity and its correlation to the metal oxidation numbers. A carbon-aerogel-supported iron (Fe/CAG) catalyst was used herein to decompose toluene (model tar) at between 500 °C and 700 °C. The catalytic decomposition was studied in a conventional reaction system, and the catalyst was characterized prior to and after the reaction to understand the effect of the structural changes in the catalytic activity. The results demonstrated that the iron oxidation state and coke deposition strongly depend on the reaction temperature. The X-ray diffraction patterns confirmed that at T < 700 °C, several Fei+ are present, while at 700 °C, Fe° prevails, suggesting a reconstruction of the metal clusters on the surface. The Fe/C ratio determined by elemental mapping (EDS), as well as thermogravimetric analysis coupled to mass spectrometry (TGA-MS) of the spent catalysts, confirmed that this surface reconstruction is related to carbothermic reduction of the metal oxides and assisted by carbon deposition.
Torrefaction is a thermal pretreatment leading to the improvement of most of the fuel properties of biomass, namely energy density, HHV (higher heating value), grindability and hydrophobicity. The ...aim of this study is to identify the most feasible temperature to carry out torrefaction of Eucalyptus globulus and nitens, based on chemical evidences associated to the release of volatiles during thermal treatment of biomass. With that end: (i) Devolatilization kinetics, (ii) Effects of temperature and residence time and (iii) volatiles composition during torrefaction of both wood and bark were analyzed. In all cases DTG (derivative thermogravimetric curves) exhibited the typical shape of lignocellulosic materials, with three decomposition phases and two reaction zones. Values of activation energies for hemicellulose decomposition, were in agreement with those reported in the literature (121–170 kJ/mol). Carboxylic acids, water and phenolic compounds showed two peaks, which were associated to torrefaction (below 310 °C) and pyrolysis (310–410 °C) respectively. The most feasible temperatures for torrefaction were estimated as a function of these peaks, and it ranged between 295 °C and 310 °C for all samples. Main volatile species at the torrefaction peaks were distributed as Water > Acetic Acid > CO2 > Others, while Levoglucosan formation was marginal, due to the catalytic effect of inorganics.
•Identification of torrefaction peaks for E. globulus and E. nitens using dynamic TGA-MS.•Devolatilization kinetics of E. globulus and E. nitens (wood and bark).•Effect of operation parameters on torrefaction of E. globulus and E. nitens.•Most feasible temperatures for torrefaction based on chemical and thermal evidences.•Definition of atomic indicator to estimate degradation degree based on TGA-MS.
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