Characterisation of mortar morphology in thin sections by digital image processing

A digital imaging approach was applied to investigate mortar morphology in thin sections; in particular, the binder/aggregate ratio and the grading curve of five mortar bars were attained by digital image processing (DIP), using the Image Pro Plus 4.1 software package. The imaging procedure employed image segmentation, to extract mortar aggregate, and image filtering, to fix grain boundaries. The results show that digital image processing may be considered as an alternative method to mechanical sieving for the characterisation of mortar morphology, as it appears to be quicker and more accurate than the traditional method. However, digital image processing exhibits limits, which are discussed in the text.     

Artificial institutions: a model of institutional reality for open multiagent systems

Software agents’ ability to interact within different open systems, designed by different groups, presupposes an agreement on an unambiguous definition of a set of concepts, used to describe the context of the interaction and the communication language the agents can use. Agents’ interactions ought to allow for reliable expectations on the possible evolution of the system; however, in open systems interacting agents may not conform to predefined specifications. A possible solution is to define interaction environments including a normative component, with suitable rules to regulate the behaviour of agents. To tackle this problem we propose an application-independent metamodel of artificial institutions that can be used to define open multiagent systems. In our view an artificial institution is made up by an ontology that models the social context of the interaction, a set of authorizations to act on the institutional context, a set of linguistic conventions for the performance of institutional actions and a system of norms that are necessary to constrain the agents’ actions.     

Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

Currently,sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients.Unfortunately,its side effects,particularly its overall toxicity,limit the therapeutic response that can be achieved.Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field,thus improving intratumoral accumulation and reducing adverse effects.Here,nanoformulations based on polyethylene glycol modified phospholipid micelles,loaded with both SPIONs and sorafenib,were successfully prepared and thoroughly investigated by complementary techniques.This nanovector system provided effective drug delivery,had an average hydrodynamic diameter of about 125 nm,had good stability in aqueous medium,and allowed controlled drug loading.Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle.An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver.Human hepatocellular carcinoma (HepG2) cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib.These experiments demonstrated that this delivery platform is able to enhance sorafenib's antitumor effectiveness by magnetic targeting.The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites,where selective release of sorafenib can improve its efficacy and safety profile.     

Detection of epileptic electroencephalogram based on Permutation Entropy and Support Vector Machines

The electroencephalogram (EEG) has proven a valuable tool in the study and detection of epilepsy. This paper investigates for the first time the use of Permutation Entropy (PE) as a feature for automated epileptic seizure detection. A Support Vector Machine (SVM) is used to classify segments of normal and epileptic EEG based on PE values. The proposed system utilizes the fact that the EEG during epileptic seizures is characterized by lower PE than normal EEG. It is shown that average sensitivity of 94.38% and average specificity of 93.23% is obtained by using PE as a feature to characterize epileptic and seizure-free EEG, while 100% sensitivity and specificity were also obtained in single-trial classifications.     

Applying EuroWordNet to Cross-Language Text Retrieval

We discuss ways in which EuroWordNet (EWN) can be used in multilingual information retrieval activities, focusing on two approaches to Cross-Language Text Retrieval that use the EWN database as a large-scale multilingual semantic resource. The first approach indexes documents and queries in terms of the EuroWordNet Inter-Lingual-Index, thus turning term weighting and query/document matching into language-independent tasks. The second describes how the information in the EWN database could be integrated with a corpus-based technique, thus allowing retrieval of domain-specific terms that may not be present in our multilingual database. Our objective is to show the potential of EuroWordNet as a promising alternative to existing approaches to Cross-Language Text Retrieval.     

The Histamine H4 Receptor Participates in the Neuropathic Pain-Relieving Activity of the Histamine H3 Receptor Antagonist GSK189254

Growing evidence points to the histamine system as a promising target for the management of neuropathic pain. Preclinical studies reported the efficacy of H₃R antagonists in reducing pain hypersensitivity in models of neuropathic pain through an increase of histamine release within the CNS. Recently, a promising efficacy of H₄R agonists as anti-neuropathic agents has been postulated. Since H₃R and H₄R are both localized in neuronal areas devoted to pain processing, the aim of the study is to investigate the role of H₄R in the mechanism of anti-hyperalgesic action of the H₃R antagonist GSK189254 in the spared nerve injury (SNI) model in mice. Oral (6 mg/kg), intrathecal (6 µg/mouse), or intra locus coeruleus (LC) (10 µg/µL) administration of GSK189254 reversed mechanical and thermal allodynia in the ipsilateral side of SNI mice. This effect was completely prevented by pretreatment with the H₄R antagonist JNJ 10191584 (6 µg/mouse i.t.; (10 µg/µL intraLC). Furthermore, GSK189254 was devoid of any anti-hyperalgesic effect in H₄R deficient mice, compared with wild type mice. Conversely, pretreatment with JNJ 10191584 was not able to prevent the hypophagic activity of GSK189254. In conclusion, we demonstrated the selective contribution of H₄R to the H₃R antagonist-induced attenuation of hypernociceptive behavior in SNI mice. These results might help identify innovative therapeutic interventions for neuropathic pain.     

The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma

Microtubule-targeting agents (MTAs) are effective drugs for cancer treatment. A novel diaryl [1,2]oxazole class of compounds binding the colchicine site was synthesized as cis-restricted-combretastatin-A-4-analogue and then chemically modified to have improved solubility and a wider therapeutic index as compared to vinca alkaloids and taxanes. On these bases, a new class of tricyclic compounds, containing the [1,2]oxazole ring and an isoindole moiety, has been synthetized, among which SIX2G emerged as improved MTA. Several findings highlighted the ability of some chemotherapeutics to induce immunogenic cell death (ICD), which is defined by the cell surface translocation of Calreticulin (CALR) via dissociation of the PP1/GADD34 complex. In this regard, we computationally predicted the ability of SIX2G to induce CALR exposure by interacting with the PP1 RVxF domain. We then assessed both the potential cytotoxic and immunogenic activity of SIX2G on in vitro models of multiple myeloma (MM), which is an incurable hematological malignancy characterized by an immunosuppressive milieu. We found that the treatment with SIX2G inhibited cell viability by inducing G2/M phase cell cycle arrest and apoptosis. Moreover, we observed the increase of hallmarks of ICD such as CALR exposure, ATP release and phospho-eIF2α protein level. Through co-culture experiments with immune cells, we demonstrated the increase of (i) CD86 maturation marker on dendritic cells, (ii) CD69 activation marker on cytotoxic T cells, and (iii) phagocytosis of tumor cells following treatment with SIX2G, confirming the onset of an immunogenic cascade. In conclusion, our findings provide a framework for further development of SIX2G as a new potential anti-MM agent.     

Characterisation of Progressive Skeletal Muscle Fibrosis in the Mdx Mouse Model of Duchenne Muscular Dystrophy: An In Vivo and In Vitro Study

Duchenne muscular dystrophy (DMD) is a rare genetic disease leading to progressive muscle wasting, respiratory failure, and cardiomyopathy. Although muscle fibrosis represents a DMD hallmark, the organisation of the extracellular matrix and the molecular changes in its turnover are still not fully understood. To define the architectural changes over time in muscle fibrosis, we used an mdx mouse model of DMD and analysed collagen and glycosaminoglycans/proteoglycans content in skeletal muscle sections at different time points during disease progression and in comparison with age-matched controls. Collagen significantly increased particularly in the diaphragm, quadriceps, and gastrocnemius in adult mdx, with fibrosis significantly correlating with muscle degeneration. We also analysed collagen turnover pathways underlying fibrosis development in cultured primary quadriceps-derived fibroblasts. Collagen secretion and matrix metalloproteinases (MMPs) remained unaffected in both young and adult mdx compared to wt fibroblasts, whereas collagen cross-linking and tissue inhibitors of MMP (TIMP) expression significantly increased. We conclude that, in the DMD model we used, fibrosis mostly affects diaphragm and quadriceps with a higher collagen cross-linking and inhibition of MMPs that contribute differently to progressive collagen accumulation during fibrotic remodelling. This study offers a comprehensive histological and molecular characterisation of DMD-associated muscle fibrosis; it may thus provide new targets for tailored therapeutic interventions.