Promotion of macrophage activation by Tie2 in the context of the inflamed synovia of rheumatoid arthritis and psoriatic arthritis patients

OBJECTIVE: To examine the role of Tie2 signalling in macrophage activation within the context of the inflammatory synovial microenvironment present in patients with RA and PsA. METHODS: Clinical responses and macrophage function were examined in wild-type and Tie2-overexpressing (Tie2-TG) mice in the K/BxN serum transfer model of arthritis. Macrophages derived from peripheral blood monocytes from healthy donors, RA and PsA patients, and RA and PsA synovial tissue explants were stimulated with TNF (10 ng/ml), angiopoietin (Ang)-1 or Ang-2 (200 ng/ml), or incubated with an anti-Ang2 neutralizing antibody. mRNA and protein expression of inflammatory mediators was analysed by quantitative PCR, ELISA and Luminex. RESULTS: Tie2-TG mice displayed more clinically severe arthritis than wild-type mice, accompanied by enhanced joint expression of IL6, IL12B, NOS2, CCL2 and CXCL10, and activation of bone marrow-derived macrophages in response to Ang-2 stimulation. Ang-1 and Ang-2 significantly enhanced TNF-induced expression of pro-inflammatory cytokines and chemokines in macrophages from healthy donors differentiated with RA and PsA SF and peripheral blood-derived macrophages from RA and PsA patients. Both Ang-1 and Ang-2 induced the production of IL-6, IL-12p40, IL-8 and CCL-3 in synovial tissue explants of RA and PsA patients, and Ang-2 neutralization suppressed the production of IL-6 and IL-8 in the synovial tissue of RA patients. CONCLUSION: Tie2 signalling enhances TNF-dependent activation of macrophages within the context of ongoing synovial inflammation in RA and PsA, and neutralization of Tie2 ligands might be a promising therapeutic target in the treatment of these diseases

Managing maize under pest species competition: is Bt (Bacillus thuringiensis) maize the solution?

Transgenic crops that contain Cry genes from Bacillus thuringiensis (Bt) have been adopted by farmers over the last 17 years. Unlike traditional broad spectrum chemical insecticides, Bt's toxicity spectrum is relatively narrow and selective, which may indirectly benefit secondary insects that may become important pests. The economic damage caused by the rise of secondary pests could offset some or all of the benefits associated with the use of Bt varieties. We develop a bioeconomic model to analyze the interactions between primary and secondary insect populations and the impact of different management options on insecticide use and economic impact over time. Results indicate that some of the benefits associated with the adoption of genetically engineered insect resistant crops may be eroded when taking into account ecological dynamics. It is suggested that secondary pests could easily become key insect pests requiring additional measures - such as insecticide applications or stacked traits – to keep their populations under the economic threshold

An overview of digital speech watermarking

Digital speech watermarking is a robust way to hide and thus secure data like audio and video from any intentional or unintentional manipulation through transmission. In terms of some signal characteristics including bandwidth, voice/non-voice and production model, digital speech signal is different from audio, music and other signals. Although, various review articles on image, audio and video watermarking are available, there are still few review papers on digital speech watermarking. Therefore this article presents an overview of digital speech watermarking including issues of robustness, capacity and imperceptibility. Other issues discussed are types of digital speech watermarking, application, models and masking methods. This article further highlights the related challenges in the real world, research opportunities and future works in this area, yet to be explored fully

Surface and subsurface flow in eucalyptus plantations in north-central Portugal

In the Baixo Vouga region of north-central Portugal, forests occupy half of the territory, of which two thirds are Eucalypts plantations. The hydrological implications of this large-scale introduction of eucalypt are unknown and the aim of this exploratory study, realized in the Caramulo Mountains, was to describe overland flow (OLF), subsurface flow (SSF) and stream flow (Q) in a catchment dominated by Eucalyptus plantations. The main conclusions are that annual OLF rate is low, spatially heterogeneous between 0.1% and 6% and concentrated during the wet season as saturation excess, particularly as return flow. Infiltration-excess OLF due to the strong soil water repellence (SWR) is dominant during dry season, but produces residual runoff amount. SSF is the principal mechanism of runoff formation. It originates from matrix flow and pipe flow at the soil-bedrock interface, principally during the wet season. Matrix flow is correlated with soil moisture (SM) content, with a threshold of 25 %. Pipe flow starts with saturation of soil bottom but without saturation of the entire soil profile, due to a large network of macropores. Stream flow response is highly correlated with matrix flow behaviour in timing and intensity. SWR induces a very patchy moistening of the soil, concentrates the fluxes and accelerates them almost 100 times greater than normal percolation of the water in the matrix

Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results.

Neuroblastomas harbor ALK aberrations clinically resistant to crizotinib yet sensitive pre-clinically to the third-generation ALK inhibitor lorlatinib. We conducted a first-in-child study evaluating lorlatinib with and without chemotherapy in children and adults with relapsed or refractory ALK-driven neuroblastoma. The trial is ongoing, and we report here on three cohorts that have met pre-specified primary endpoints: lorlatinib as a single agent in children (12 months to <18 years); lorlatinib as a single agent in adults (≥18 years); and lorlatinib in combination with topotecan/cyclophosphamide in children (<18 years). Primary endpoints were safety, pharmacokinetics and recommended phase 2 dose (RP2D). Secondary endpoints were response rate and 123I-metaiodobenzylguanidine (MIBG) response. Lorlatinib was evaluated at 45-115 mg/m2/dose in children and 100-150 mg in adults. Common adverse events (AEs) were hypertriglyceridemia (90%), hypercholesterolemia (79%) and weight gain (87%). Neurobehavioral AEs occurred mainly in adults and resolved with dose hold/reduction. The RP2D of lorlatinib with and without chemotherapy in children was 115 mg/m2. The single-agent adult RP2D was 150 mg. The single-agent response rate (complete/partial/minor) for <18 years was 30%; for ≥18 years, 67%; and for chemotherapy combination in <18 years, 63%; and 13 of 27 (48%) responders achieved MIBG complete responses, supporting lorlatinib's rapid translation into active phase 3 trials for patients with newly diagnosed high-risk, ALK-driven neuroblastoma. ClinicalTrials.gov registration: NCT03107988

Experimental Studies on Bond Performance of BFRP bars reinforced Coral Aggregate Concrete

As part of this study, has been developed a numerical method which allows to establish abacuses connecting the normal force with bending moment for a circular section and therefore to predict the rupture of this type of section. This may be for reinforced concrete (traditional steel) or concrete reinforced with steel fibers. The numerical simulation was performed in nonlinear elasticity up to exhaustion of the bearing capacity of the section. The rupture modes considered occur by plasticization of the steel or rupture of the concrete (under compressive stresses or tensile stresses). Regarding the fiber-reinforced concrete, the rupture occurs, usually, by tearing of the fibers. The behavior laws of the different materials (concrete and steel) correspond to the real behavior. The influence of several parameters was investigated, namely; diameter of the section, concrete strength, type of steel, percentage of reinforcement and contribution of concrete in tension between two successive cracks of bending. A comparison was made with the behavior of a section considering the conventional diagrams of materials; provided by the BAEL rules. A second comparative study was performed for fibers reinforced section

Identification of four families of yCCR4- and Mg(2+)-dependent endonuclease-related proteins in higher eukaryotes, and characterization of orthologs of yCCR4 with a conserved leucine-rich repeat essential for hCAF1/hPOP2 binding

BACKGROUND: The yeast yCCR4 factor belongs to the CCR4-NOT transcriptional regulatory complex, in which it interacts, through its leucine-rich repeat (LRR) motif with yPOP2. Recently, yCCR4 was shown to be a component of the major cytoplasmic mRNA deadenylase complex, and to contain a fold related to the Mg(2+)-dependent endonuclease core. RESULTS: Here, we report the identification of nineteen yCCR4-related proteins in eukaryotes (including yeast, plants and animals), which all contain the yCCR4 endonuclease-like fold, with highly conserved CCR4-specific residues. Phylogenetic and genomic analyses show that they form four distinct families, one of which contains the yCCR4 orthologs. The orthologs in animals possess a leucine-rich repeat domain. We show, using two-hybrid and far-Western assays, that the human member binds to the human yPOP2 homologs, i.e. hCAF1 and hPOP2, in a LRR-dependent manner. CONCLUSIONS: We have identified the mammalian orthologs of yCCR4 and have shown that the human member binds to the human yPOP2 homologs, thus strongly suggesting conservation of the CCR4-NOT complex from yeast to human. All members of the four identified yCCR4-related protein families show stricking conservation of the endonuclease-like catalytic motifs of the yCCR4 C-terminal domain and therefore constitute a new family of potential deadenylases in mammals

Cognitive Information Processing

Contains goals, background, research activities on one research project and reports on three research projects.Center for Advanced Television StudiesAmerican Broadcasting CompanyAmpex CorporationColumbia Broadcasting SystemsHarris CorporationHome Box OfficePublic Broadcasting ServiceNational Broadcasting CompanyRCA CorporationTektronix3M CompanyProvidence Gravure Co. (Grant)International Business Machines, Inc