Sulphated and Non-sulphated Disaccharides: Cellular And Molecular Mechanisms of Action in Macrophage Function

Sulphated disaccharides are degradation products of heparinase that are released by inflammatory cells at sites of inflammation. Recent studies have shown that heparin derived sulphated disaccharides inhibit macrophage TNF-α synthesis, delayed-type hypersensitivity, rat adjuvant and rat and mouse collagen induced arthritis, with indications that they act on T-cell and macrophage function. The mechanisms by which these occur are unknown. Therefore, this study aims to investigate the mechanism of action of sulphated disaccharides through which they produce an inhibitory effect. In this study, the impact of sulphated disaccharides was tested on monocyte-macrophage functions in vitro. In this study, it was established that sulphated disaccharides inhibit PMAstimulated macrophage-like cell differentiation (10⁻¹¹ – 10⁻⁴ M). The reduced numbers of adherent macrophages cells leads to the reduction of proinflammatory macrophages. Inhibition of phosphorylation of p38 and ERK1/2 was found and was directly proportional to sulphated disaccharide structural features, namely selective (HDS-I, HDS-III) or oligosulphation (SOS, DOS). Preincubation of monocytes with sulphated disaccharides inhibited PMA-induced calcium mobilisation. In addition, this study demonstrated that treatment with sulphated disaccharides induces a phenotypic switch of differentiated macrophages into an anti-inflammatory phenotype and also the pro-inflammatory phenotype into an anti-inflammatory phenotype. The current study provides an insight into the possibility of targeting inhibition of monocyte-macrophage-differentiation through inhibition of calcium mobilisation, leading to de-activation of p38 and ERK1/2 MAPK, TNF-α production, and ultimately inhibition of cell-differentiation induced cell surface adhesion molecule expression. In addition, sulphated disaccharides promote macrophage divergence towards an anti-inflammatory phenotype. The findings of this study indicate that sulphate disaccharides exhibit their inhibitory action even at very low concentrations, especially the oligosulphated compounds. Thus, suggesting a novel molecular mechanism for the treatment of macrophage-dependent chronic inflammatory diseases

Target Estimation in Colocated MIMO Radar via Matrix Completion

We consider a colocated MIMO radar scenario, in which the receive antennas forward their measurements to a fusion center. Based on the received data, the fusion center formulates a matrix which is then used for target parameter estimation. When the receive antennas sample the target returns at Nyquist rate, and assuming that there are more receive antennas than targets, the data matrix at the fusion center is low-rank. When each receive antenna sends to the fusion center only a small number of samples, along with the sample index, the receive data matrix has missing elements, corresponding to the samples that were not forwarded. Under certain conditions, matrix completion techniques can be applied to recover the full receive data matrix, which can then be used in conjunction with array processing techniques, e.g., MUSIC, to obtain target information. Numerical results indicate that good target recovery can be achieved with occupancy of the receive data matrix as low as 50%.Comment: 5 pages, ICASSP 201

StemNet: An Evolving Service for Knowledge Networking in the Life Sciences

Up until now, crucial life science information resources, whether bibliographic or factual databases, are isolated from each other. Moreover, semantic metadata intended to structure their contents is supplied in a manual form only. In the StemNet project we aim at developing a framework for semantic interoperability for these resources. This will facilitate the extraction of relevant information from textual sources and the generation of semantic metadata in a fully automatic manner. In this way, (from a computational perspective) unstructured life science documents are linked to structured biological fact databases, in particular to the identifiers of genes, proteins, etc. Thus, life scientists will be able to seamlessly access information from a homogeneous platform, despite the fact that the original information was unlinked and scattered over the whole variety of heterogeneous life science information resources and, therefore, almost inaccessible for integrated systematic search by academic, clinical, or industrial users

Optimization of the level of ingredients for functional dairy beverage using response surface methodology (RSM)

The present investigation was undertaken to optimize the level of ingredients (milk fat, sugar, and mango pulp) for functional dairy beverage using Response Surface Methodology. Central Composite Rotatable Design with milk fat (%), sugar (%), and mango pulp (var. Chaunsa, %) as independent variables produced 20 different combinations that were used to investigate the effect on viscosity (cP), antioxidant activity, and overall acceptability. The response surface three dimensional graphs were plotted as a function of two variables to show the effect of level of ingredients on physico-chemical and sensory properties of the beverage. Significant correlation models were established with the coefficient of correlation (R2) greater than 0.8. An optimization of process variables was attempted for maximum antioxidant activity and overall acceptability. ANOVA tables revealed that increase in fat and sugar levels lowered the antioxidant activity, while enhancement of mango pulp significantly increased both antioxidant activity and overall acceptability of the beverage. The optimized levels of ingredients were 0.5% milk fat, 6.0% sugar and 30% mango pulp

Low temperature heat release and ϕ-sensitivity characteristics of iso-octane/air mixtures

Chemical energy release from high octane number fuels via low temperature heat release (LTHR) can help develop high-efficiency gasoline engines by promoting ultra-lean combustion in spark ignition engines and improving combustion control in gasoline compression ignition engines. A recently developed experimental technique that permits isolated LTHR investigations in motored engines was used to characterize the LTHR behavior of iso-octane/air mixtures ranging in strength from ϕ≈0.02 to 1.6 at multiple inlet temperature conditions (60 to 120°C). LTHR changes were studied by observing variations in exhaust CO emissions and exhaust temperature increase. Observed heat release results were explained using cylinder mixture pressure-temperature histories alongside supporting chemical kinetics modeling estimates of mixture reactivity in the form of chemical ignition delay (ID) time. The effects of fuel enrichment on iso-octane/air mixture reactivity were found to be non-uniform and dependent on mixtures’ thermal state trajectories in the LTHR ID peninsula. LTHR intensity measurements were used to discuss changes in mixture ϕ−sensitivity at different engine inlet conditions. It was shown that by appropriately adjusting mixture thermal conditions via charge cooling from direct fuel injection and intake air heating, reactivity enhancements could be exploited maximally; and strong, positive, linear ϕ−sensitivity of around 10 J per 0.1 increase in ϕ could be realized across a wide range of equivalence ratios from 0.05–1.2. It was also found that dominance of charge cooling effects at rich conditions resulted in negative and zero ϕ−sensitivity regions

Fabrication and characterisation of electrodeposited and magnetron sputtered thin films

The MnO-Zn thin films were fabricated by radio frequency (RF) magnetron sputtering and compared with pulse electrodeposition (PED) Zn thin films, doped with MnO and ZrO nanoparticles. Surface morphology, structural properties, chemical composition and corrosion resistance of these coatings were investigated by using Scanning Electron Microscopic (SEM), X-ray Diffraction (XRD), Energy-dispersive X-ray Spectroscopy (EDS), 3-D Scanning Interferometry and environmental chamber. Surface morphology and degree of crystallinity have different behaviour for differen t deposi tion method. Pulse coated films have polycrystalline structure with high surface roughness (Ra) whereas sputtered films are mono-crystalline with reduced roughness (Ra). Corrosion tests of both RF sputter and PED films revealed that the distribution of corrosion products formed on the surface of sputter films were not severe in extent as in case of electrodeposited coatings. Results showed that the doping of ZrO nano-sized particles in Zn matrix and Mn-Zn composite films significantly improved the corrosion resistance of PED thin films

Fabrication and characterisation of electrodeposited and magnertron-sputtered thin films

The MnO–Zn thin films were fabricated by radio frequency (RF) magnetron sputtering and compared with pulse electrodeposition (PED) Zn thin films, doped with MnO and ZrO nanoparticles. Surface morphology, structural properties, chemical composition and corrosion resistance of these coatings were investigated by using scanning electron microscopy, X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy, 3-D scanning interferometry and environmental chamber. Surface morphology and degree of crystallinity have different behaviours for different deposition methods. Pulse-coated films have polycrystalline structure with high surface roughness (Ra), whereas sputtered films are monocrystalline with reduced roughness (Ra). Corrosion tests of both RF sputter and PED films revealed that the distribution of corrosion products formed on the surface of sputter films were not severe in extent as in case of electrodeposited coatings. Results showed that the doping of ZrO nano-sized particles in Zn matrix and Mn–Zn composite films significantly improved the corrosion resistance of PED thin films. Keywords: Corrosion resistance, electro-deposition, magnetron sputtering, surface analysis, thin films

The use of urinary proteomics in the assessment of suitability of mouse models for ageing

Ageing is a complex process characterised by a systemic and progressive deterioration of biological functions. As ageing is associated with an increased prevalence of age-related chronic disorders, understanding its underlying molecular mechanisms can pave the way for therapeutic interventions and managing complications. Animal models such as mice are commonly used in ageing research as they have a shorter lifespan in comparison to humans and are also genetically close to humans. To assess the translatability of mouse ageing to human ageing, the urinary proteome in 89 wild-type (C57BL/6) mice aged between 8–96 weeks was investigated using capillary electrophoresis coupled to mass spectrometry (CE-MS). Using age as a continuous variable, 295 peptides significantly correlated with age in mice were identified. To investigate the relevance of using mouse models in human ageing studies, a comparison was performed with a previous correlation analysis using 1227 healthy subjects. In mice and humans, a decrease in urinary excretion of fibrillar collagens and an increase of uromodulin fragments was observed with advanced age. Of the 295 peptides correlating with age, 49 had a strong homology to the respective human age-related peptides. These ortholog peptides including several collagen (N = 44) and uromodulin (N = 5) fragments were used to generate an ageing classifier that was able to discriminate the age among both wild-type mice and healthy subjects. Additionally, the ageing classifier depicted that telomerase knock-out mice were older than their chronological age. Hence, with a focus on ortholog urinary peptides mouse ageing can be translated to human ageing

Changing and pivoting the business model in software startups

In a company, its business strategy and business model undergo changes throughout its life. These changes can be induced or forced externally or they can result from a deliberate strategy to improve the business performance and to achieve success. Certain changes can lead to a major change in the business model of the company (i.e., a pivot). Such change or innovation in the business model can occur in various of its dimensions. According to Osterwalder and Pigneur, there are four epicenters of change and innovation to be taken into consideration. In this manuscript, fifteen Portuguese software startups were studied using essentially semi-structured interviews to gather the information. The data was processed with a software application for qualitative data analysis. The main results are related to a dynamic process of evolution and change of the business model in software startups. In particular, we have identified that the changes in the business elements that support the production of the value proposition (left-hand side of the Business Model Canvas) affect the elements that explain the strategy of delivering the value proposition to customers (right-hand side of the Business Model Canvas).This work was supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT Fundação para a Ciência e a Tecnologia within the Project Scope: UID/CEC/00319/2013