The impacts of a GTL plant on Brazil's oil products supply and refinery expansion

This paper assesses the impacts of a GTL plant on the expansion of Brazil's oil refining segment. The GTL plant (50,000 bpd) was sized to start up operations in 2015, producing diesel and naphtha through the indirect route (FT-synthesis). This plant will consume the non-associated natural gas production from the recent discoveries at the Santos Basin (around 419 Bm³), and the associated gas production from the Campos Basin. Both basins are located in the Southeast of Brazil, the most populated, rich and industrialized region of the country. Two different criteria for refinery expansion were simulated in order to meet oil product demand scenarios. Findings show that depending on the refinery expansion criteria considered GTL will play a fundamental hole to meet the oil product demand forecast to Brazil in the next 10 years.     

Metal sorption by biomass of melanin‐producing fungi grown in clay‐containing medium

The sorption of toxic metals by fungal mycelia grown in clay‐containing medium is reported in this work. Biomass of melanin‐producing microfungi of the genus Cladosporium (C cladosporioides, C resinae and C herbarum) and Aureobasidium pullulans, clay minerals and fungal mycelia grown in clay‐containing medium were compared for their equilibrium Cu and Cd uptake from pH‐buffered solutions using experimental sorption isotherms. Bentonite (Cherkassy) in the natural form was shown to be the best Cu sorbent compared with the other clays and clay minerals tested. Cu sorption isotherms fitted the Langmuir sorption model for all cases. Comparison of Cu and Cd uptake for biomass and bentonite showed a lower biomass uptake capacity but a considerably higher affinity of the biosorbent for the solute. The presence of kaolinite and palygorskite in the medium generally reduced both Cu and Cd sorption capacity and the metal‐binding ability of the fungal–clay mixtures. In contrast, addition of bentonite into the medium did not appreciably alter the Cd sorption ability but increased the sorption of Cu by A pullulans and C cladosporioides grown in this medium. A common feature for all fungi grown in the presence of bentonite was an increase in the Cu sorption capacity (Q_max) of the biomineral sorbents and a reduction in their affinity (Langmuir parameter b) compared with control biomass. A difference between predicted and experimental data obtained for biomass grown on bentonite medium was also observed. The connection between the sorption capacity of biomass grown in clay‐containing medium, mycelial morphology and the structure of fungal pellets is discussed and a mechanism for the changed sorption capacity of the combined biomineral sorbents is proposed which involves blocking or modification of binding sites on biotic and abiotic components of the ‘biomineral’ association. © 2002 Society of Chemical Industry     

Embodied Robot versus Virtual Agent: Involvement of Preschool Children in Motor Task Performance

Embodied robots are known to be preferable in most cases to their virtual agents for interaction with and performance by human subjects. This study compared the efficacy of an embodied robot-coacher and its virtual agent in involving preschool children in the performance of playlike motor tasks. The robot or its virtual agent demonstrated movements, asked the children to repeat them, and provided positive feedback on their performance. The difficulty of the motor tasks was increased over the course of the session. Two groups of children were studied, one of them with and the other without previous experience of interaction with the embodied robot. In the experienced group, involvement in motor tasks was successfully induced by both the embodied robot and its virtual agent, but the children interacted less well with the virtual agent than with the embodied robot. Children in the inexperienced group did not interact at all during the experiment with the virtual agent. Because participants in the experiment were preschool children in their natural environment, this study proposes the combined use of an embodied robot and its virtual agent for motor involvement.     

Ab initio determination of heavy oxide perovskite related structures from precession electron diffraction data

Two complex perovskite-related structures were solved by ab initio from precession electron diffraction intensities. Structure models were firstly derived from HREM images and than have been confirmed independently using two and three-dimensional sets of precession intensities. Patterson techniques prove to be effective for ab initio structure resolution, specially in case of projections with no overlapping atoms. Quality of precession intensity data may be suitable enough to resolve unknown heavy oxide structures.     

Neutrophils Mediate Pulmonary Artery Thrombosis In Situ

Pulmonary embolism is a life-threatening condition, which can result in respiratory insufficiency and death. Blood clots occluding branches of the pulmonary artery (PA) are traditionally considered to originate from thrombi in deep veins (usually in legs). However, growing evidence suggests that occlusion of the vessels in the lungs can develop without preceding deep vein thrombosis (DVT). In this work, we used an inferior vena cava (IVC) complete ligation model of DVT in Wistar rats to explore the possibility and mechanisms of PA thrombosis under the conditions where all routes of thrombotic mass migration from peripheral veins are blocked. We demonstrate that rats both with normal and reduced neutrophil counts developed thrombi in the IVC, although, neutropenia caused a substantial decrease in thrombus size and a shift from fresh fibrin toward mature fibrin and connective tissue inside the thrombus. Massive fibrin deposition was found in the PA branches in the majority of DVT rats with normal neutrophil counts, but in none of the neutropenic animals. Neutrophil ablation also abolished macroscopic signs of lung damage. Altogether, the results demonstrate that thrombi in the lung vasculature can form in situ by mechanisms that require local neutrophil recruitment taking place in the DVT setting.     

The State of the Art of Piezo1 Channels in Skeletal Muscle Regeneration

Piezo1 channels are highly mechanically-activated cation channels that can sense and transduce the mechanical stimuli into physiological signals in different tissues including skeletal muscle. In this focused review, we summarize the emerging evidence of Piezo1 channel-mediated effects in the physiology of skeletal muscle, with a particular focus on the role of Piezo1 in controlling myogenic precursor activity and skeletal muscle regeneration and vascularization. The disclosed effects reported by pharmacological activation of Piezo1 channels with the selective agonist Yoda1 indicate a potential impact of Piezo1 channel activity in skeletal muscle regeneration, which is disrupted in various muscular pathological states. All findings reported so far agree with the idea that Piezo1 channels represent a novel, powerful molecular target to develop new therapeutic strategies for preventing or ameliorating skeletal muscle disorders characterized by an impairment of tissue regenerative potential.     

Novel Epoxides of Soloxolone Methyl: An Effect of the Formation of Oxirane Ring and Stereoisomerism on Cytotoxic Profile,Anti-Metastatic and Anti-Inflammatory Activities In Vitro and In Vivo

It is known that epoxide-bearing compounds display pronounced pharmacological activities, and the epoxidation of natural metabolites can be a promising strategy to improve their bioactivity. Here, we report the design, synthesis and evaluation of biological properties of αO-SM and βO-SM, novel epoxides of soloxolone methyl (SM), a cyanoenone-bearing derivative of 18βH-glycyrrhetinic acid. We demonstrated that the replacement of a double-bound within the cyanoenone pharmacophore group of SM with α- and β-epoxide moieties did not abrogate the high antitumor and anti-inflammatory potentials of the triterpenoid. It was found that novel SM epoxides induced the death of tumor cells at low micromolar concentrations (IC₅₀^(24h) = 0.7–4.1 µM) via the induction of mitochondrial-mediated apoptosis, reinforced intracellular accumulation of doxorubicin in B16 melanoma cells, probably by direct interaction with key drug efflux pumps (P-glycoprotein, MRP1, MXR1), and the suppressed pro-metastatic phenotype of B16 cells, effectively inhibiting their metastasis in a murine model. Moreover, αO-SM and βO-SM hampered macrophage functionality in vitro (motility, NO production) and significantly suppressed carrageenan-induced peritonitis in vivo. Furthermore, the effect of the stereoisomerism of SM epoxides on the mentioned bioactivities and toxic profiles of these compounds in vivo were evaluated. Considering the comparable antitumor and anti-inflammatory effects of SM epoxides with SM and reference drugs (dacarbazine, dexamethasone), αO-SM and βO-SM can be considered novel promising antitumor and anti-inflammatory drug candidates.     

MIL-100(Fe) Sub-Micrometric Capsules as a Dual Drug Delivery System

Nanoparticles of metal–organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTX@COL@MIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment.     

Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma

Glioblastoma (GBM) is the most common tumor in the central nervous system in adults. This neoplasia shows a high capacity of growth and spreading to the surrounding brain tissue, hindering its complete surgical resection. Therefore, the finding of new antitumor therapies for GBM treatment is a priority. We have previously described that cyclin D1-CDK4 promotes GBM dissemination through the activation of the small GTPases RalA and RalB. In this paper, we show that RalB GTPase is upregulated in primary GBM cells. We found that the downregulation of Ral GTPases, mainly RalB, prevents the proliferation of primary GBM cells and triggers a senescence-like response. Moreover, downregulation of RalA and RalB reduces the viability of GBM cells growing as tumorspheres, suggesting a possible role of these GTPases in the survival of GBM stem cells. By using mouse subcutaneous xenografts, we have corroborated the role of RalB in GBM growth in vivo. Finally, we have observed that the knockdown of RalB also inhibits cell growth in temozolomide-resistant GBM cells. Overall, our work shows that GBM cells are especially sensitive to Ral-GTPase availability. Therefore, we propose that the inactivation of Ral-GTPases may be a reliable therapeutic approach to prevent GBM progression and recurrence.     

S-Adenosylmethionine Inhibits Colorectal Cancer Cell Migration through Mirna-Mediated Targeting of Notch Signaling Pathway

Metastasis is a leading cause of mortality and poor prognosis in colorectal cancer (CRC). Thus, the identification of new compounds targeting cell migration represents a major clinical challenge. Recent findings evidenced a central role for dysregulated Notch in CRC and a correlation between Notch overexpression and tumor metastasis. MicroRNAs (miRNAs) have been reported to cross-talk with Notch for its regulation. Therefore, restoring underexpressed miRNAs targeting Notch could represent an encouraging therapeutic approach against CRC. In this context, S-adenosyl-L-methionine (AdoMet), the universal biological methyl donor, being able to modulate the expression of oncogenic miRNAs could act as a potential antimetastatic agent. Here, we showed that AdoMet upregulated the onco-suppressor miRNAs-34a/-34c/-449a and inhibited HCT-116 and Caco-2 CRC cell migration. This effect was associated with reduced expression of migration-/EMT-related protein markers. We also found that, in colorectal and triple-negative breast cancer cells, AdoMet inhibited the expression of Notch gene, which, by luciferase assay, resulted the direct target of miRNAs-34a/-34c/-449a. Gain- and loss-of-function experiments with miRNAs mimics and inhibitors demonstrated that AdoMet exerted its inhibitory effects by upregulating miRNAs-34a/-34c/-449a. Overall, these data highlighted AdoMet as a novel Notch inhibitor and suggested that the antimetastatic effects of AdoMet involve the miRNA-mediated targeting of Notch signaling pathway.