TNF-α Affects Signature Cytokines of Th1 and Th17 T Cell Subsets through Differential Actions on TNFR1 and TNFR2

Tumor necrosis factor (TNF)-α is a pleiotropic cytokine implicated in the etiology of several autoimmune diseases, including rheumatoid arthritis (RA). TNF-α regulates diverse effector functions through the activation of TNF-α receptor (TNFR)1 and TNFR2. Although the detrimental role of this cytokine has been addressed in distinct disease settings, the effects of TNF-α on cytokine production by isolated CD4⁺ T helper type 1 (Th1) and Th17 cells, two T cell subpopulations that contribute to the pathogenesis of RA, have not been completely elucidated. Here, we show that TNF-α promotes a reduction and expansion in the frequency of both T cell subsets producing IFN-γ and IL-17, respectively. Selective blockade of TNFR1 or TNFR2 on Th1 and Th17 cells revealed that TNFR2 mediates the decrease in IFN-γ production, while signaling through both receptors augments IL-17 production. We also demonstrate that Th1, but not Th17 cells from RA patients present lower levels of TNFR1 compared to healthy controls, whereas TNFR2 expression on both T cell types is similar between patients and controls. Since TNF-α receptors levels in RA patients are not significantly changed by the therapeutic blockade of TNF-α, we propose that targeting TNFR2 may represent an alternative strategy to normalize the levels of key cytokines that contribute to RA pathogenesis.     

Earthquakes and children: The role of psychologists with families and communities.

The 2008 Sichuan Province earthquake and 2005 Pakistan earthquake are examples of natural disasters that took an unimaginable toll on children. In such disaster management contexts, family members as well as health care and school personnel are the first-line responders and are natural sources of continued social support as children recover. Although psychologists have increasingly sophisticated understandings of post-disaster reactions and strategies for helping children and adolescents cope with trauma, models for responding to mass catastrophes are limited, particularly in geographically remote communities and in regions in which mental health services are stigmatizing. With children’s well-being subsequent to earthquakes inextricably linked to family and community, psychologists can make important contributions in 3 spheres: (a) coordinating and activating collaborations within children’s existing social contexts to develop post-earthquake interventions; (b) designing prevention and preparedness programs focused on the emotional needs of children in earthquake-prone communities; and (c) conducting research on interventions and recovery with particular attention to developmental stage, sociocultural-economic contexts, and the similarities versus differences across various types of disasters. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estimation of water diffusivity parameters on grape dynamic drying

A computer program was developed, aiming at estimating water diffusivity parameters in a dynamic drying process with grapes, assessing the predictability of corresponding non-isothermal drying curves. It numerically solves Fick’s second law for a sphere, by explicit finite differences, in a shrinking system, with anisotropic properties and changing boundary conditions.     

Intelligent control system for extractive distillation columns

We developed and implemented an intelligent control system to be used in an extractive distillation column that produces anhydrous ethanol using ethylene glycol as solvent. The concept of artificial neural networks (ANN) was used to predict new setpoints after disturbances, and proved to be a fast and feasible solution. The developed control system receives data from temperature, flowrate and composition measurements of the azeotrope feed, and the ANN estimates the new set-points of the controllers to maintain 99.5 mol% of ethanol at the top and less than 0.1mol% at the bottom; feed composition was also estimated using an ANN. All ANN were trained to provide output data corresponding to an optimized operating condition. The results showed that the intelligent control system can predict a new operating condition for any disturbance in the column feed and presented superior performance when compared with the control system without ANN.     

Thermal stability of nanometric TiC-carbon composites: effects of carbon allotropes and Zr milling impurities

In the ISOL (Isotope Separator OnLine) method a target at high temperatures (up to 2300?°C), is bombarded with high energy protons in order to produce isotopes through nuclear reactions which are simultaneously extracted from the target, ionized and delivered to physics experiments. Due to the enhanced isotope release properties of nanosized porous materials, titanium carbide-carbon porous nanocomposites have been developed at CERN and tested up to 1500?°C. In the interest of the ISOL application, in this study we extended the range of temperatures up to 1800?°C, to test the sintering hindering capabilities of different carbon allotropes. Carbon black was the most effective with the smallest TiC crystallite size: <80?nm at 1800?°C. Additionally, using thermodynamic modelling, ex-situ X-ray powder diffraction and in-situ gas phase analysis, we show that there are interesting additional phase and lattice parameter changes due to the ZrO₂ impurities from the attrition milling.     

Bonding ability of self-adhesive resin-cements after dentin biomodification with hyaluronic acid

Purpose: The present study evaluated the influence of the hyaluronic acid (HA) on the bonding ability of self-adhesive resin cements to dentin regarding the bond strength. Eighty bovine incisors were ground flat to obtain a 2-mm thick slices which received conical preparations. The specimens were randomly distributed into 4 groups (n = 15) according to the dentin pretreatment (1 – control: untreated dentin; 2 – application of HA) and the evaluation time (1 – control: immediate evaluation; 2 – hydrolytic degradation: 6 months of storage in water at 37 °C). Preparations received the application of a self-adhesive resin cement (RelyX U200 or MaxCem Elite). Push-out bond strength test was conducted (0.5 mm/min). The bond strength data was submitted to two-way ANOVA/Tukey’s test (α = 0.05). For U200, no significance was observed when comparing the immediate (24 h) and 6 months means for the control groups (unexposed specimens). Previous application of HA to dentin significantly reduced the bond strength of U200 to dentin in both evaluation times (p < 0.05). HA had no significant influence on the push-out bond strength means for the cement MAX in both evaluation times (p > 0.05). The type 1 failure mode (adhesive mode) occurred in 100% of the specimens, irrespective of the dentin treatment or evaluation times. Pretreatment of dentin with HA produces a material-dependent influence on the push-out bond strength. The bonding ability of RelyX U200 is negatively influenced by the pretreatment of dentin with HA, whereas the biomodification of dentin with this bioactive agent causes no impact for the cement MaxCem Elite.     

Characterization of functionalized multiwalled carbon nanotubes and application as an effective filter for heavy metal removal from aqueous solutions☆

Filtration efficiency of Ni(II) from aqueous solution using pristine and modified MWCNTs filters was investigated as a function of Ni(II) ion concentration, pH, and filter mass. MWCNTs were synthesized by CVD method and modified using two complementary treatments, purification (using a mixture of hydrochloric acid and hydrogen peroxide) and functionalization (using nitric acid). The effect and mechanism of each treatment on the structural integrity of pristine MWCNTs has been studied. Morphology of the pristine and modified filters was investigated by Raman Spectrometry (RS), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), Fourier Transform Infrared (FTIR) spectrometry and Thermogravimetric analysis. It was found from Raman spec-tra that the ratio of the intensity of D-band to that of G-band decreased by purification process, and increased by functionalization process. The adsorption mechanism of Ni(II) onto the surface functional groups of modified MWCNTs was confirmed by FTIR spectrum. The filtration results showed that the removal efficiency of Ni(II) is strongly dependent on pH and could reach 85%at pH=8. Also, modified MWCNT filters can be reused through many cycles of regeneration with high performance. Functionalized MWCNTs filters may be a promising adsor-bent candidate for heavy metal removal from wastewater.     

Poly(hexylacrylate)Core‐poly(ethyleneglycol methacrylate)Shell nanogels as fillers for poly(2‐hydroxyethyl methacrylate) nanocomposite hydrogels

The preparation of poly(hexylacrylate)_core‐poly(ethyleneglycol methacrylate)_shell (PHA‐co‐PEGMA) nanogels, to be used as fillers in nanocomposite hydrogels, is reported. Stable nanogels with particle sizes between 90–300 nm were obtained varying the conditions of synthesis. The synthesis recipe of the nanogels could be easily scaled up. Purified and dispersed nanogels in aqueous solution were used as soft fillers for poly(2‐hydroxyethyl methacrylate) (PHEMA) hydrogels, crosslinked with ethylene glycol dimethacrylate (EGDMA). The obtained nanocomposite hydrogels exhibit a larger swelling capacity and a higher thermal stability in comparison with the non‐filled PHEMA hydrogels. Young, storage, and lost moduli, increase largely, in the better case up to 72.5% in the swollen state; while in the dry state the storage modulus increase up to 4.7 fold with a very low load on nanogels (0.64 wt%); resulting in biomaterials with improved properties with potential applications in medical devices. POLYM. ENG. SCI., 59:170–181, 2019. © 2018 Society of Plastics Engineers     

Identification of Phenylpyrazolone Dimers as a New Class of Anti-Trypanosoma cruzi Agents

Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in-house library led to the identification of 2,2′-methylenebis(5-(4-bromophenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC₅₀ value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′-methylenebis(5-(3-bromo-4-methoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0228) as the most potent analogue. NPD-0228 has an in vitro pIC₅₀ value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC-5 cell line and murine cardiac cells.