Immunomodulatory Effect of Toll-Like Receptor-3 Ligand Poly I:C on Cortical Spreading Depression

The release of inflammatory mediators following cortical spreading depression (CSD) is suggested to play a role in pathophysiology of CSD-related neurological disorders. Toll-like receptors (TLR) are master regulators of innate immune function and involved in the activation of inflammatory responses in the brain. TLR3 agonist poly I:C exerts anti-inflammatory effect and prevents cell injury in the brain. The aim of the present study was to examine the effect of systemic administration of poly I:C on the release of cytokines (TNF-α, IFN-γ, IL-4, TGF-β1, and GM-CSF) in the brain and spleen, splenic lymphocyte proliferation, expression of GAD65, GABAAα, GABAAβ as well as Hsp70, and production of dark neurons after induction of repetitive CSD in juvenile rats. Poly I:C significantly attenuated CSD-induced production of TNF-α and IFN-γ in the brain as well as TNF-α and IL-4 in the spleen. Poly I:C did not affect enhancement of splenic lymphocyte proliferation after CSD. Administration of poly I:C increased expression of GABAAα, GABAAβ as well as Hsp70 and decreased expression of GAD65 in the entorhinal cortex compared to CSD-treated tissues. In addition, poly I:C significantly prevented production of CSD-induced dark neurons. The data indicate neuroprotective and anti-inflammatory effects of TLR3 activation on CSD-induced neuroinflammation. Targeting TLR3 may provide a novel strategy for developing new treatments for CSD-related neurological disorders. © 2014, Springer Science+Business Media New York

Immunomodulatory Effect of Toll-Like Receptor-3 Ligand Poly I:C on Cortical Spreading Depression

The release of inflammatory mediators following cortical spreading depression (CSD) is suggested to play a role in pathophysiology of CSD-related neurological disorders. Toll-like receptors (TLR) are master regulators of innate immune function and involved in the activation of inflammatory responses in the brain. TLR3 agonist poly I:C exerts anti-inflammatory effect and prevents cell injury in the brain. The aim of the present study was to examine the effect of systemic administration of poly I:C on the release of cytokines (TNF-α, IFN-γ, IL-4, TGF-β1, and GM-CSF) in the brain and spleen, splenic lymphocyte proliferation, expression of GAD65, GABAAα, GABAAβ as well as Hsp70, and production of dark neurons after induction of repetitive CSD in juvenile rats. Poly I:C significantly attenuated CSD-induced production of TNF-α and IFN-γ in the brain as well as TNF-α and IL-4 in the spleen. Poly I:C did not affect enhancement of splenic lymphocyte proliferation after CSD. Administration of poly I:C increased expression of GABAAα, GABAAβ as well as Hsp70 and decreased expression of GAD65 in the entorhinal cortex compared to CSD-treated tissues. In addition, poly I:C significantly prevented production of CSD-induced dark neurons. The data indicate neuroprotective and anti-inflammatory effects of TLR3 activation on CSD-induced neuroinflammation. Targeting TLR3 may provide a novel strategy for developing new treatments for CSD-related neurological disorders. © 2014, Springer Science+Business Media New York

Spatial and temporal variability of brittle star (Macrophiothrix cheneyi: Ophiuroidea) in the shores of Chabahar Bay, Oman Sea

Echinoderm species are important members of benthic communities existing in subtropical to Polar Regions. They have an important role in nutrient cycles and other communications between organisms. This study investigated the distribution and abundance of brittle star Macrophiothrix cheneyi in the intertidal zone of Chabahar bay, the Oman Sea. Sampling was randomly done bimonthly using a square meter quadrate during one year, from November 2008 to September 2009, at 5 selected stations. According to the results of a Kruskal-Wallis analysis, the density of this species at different sampling times and stations revealed a significant difference (P<0/05). The highest frequency of this species was measured at the station of Chabahar University of Maritime and Marine Science in September 2008 (±1/54 3/58 ind.m^-2) and its lowest frequency was measured at Kolbe Qavasi station during the whole year except January. The difference in abundance (between the different months and stations) seems to be influenced by ecological (bed, food and shelter) and biological factors (fertility, hunting and competition). The investigation of distribution revealed that brittle stars in the intertidal zone under study followed random and patchy dispersion. The results of the stability indicator revealed that though the brittle star was rarely found during some periods, it was a common species in September 2008

Composition of Constraint, Hypothesis and Error Models to improve interaction in Human-Machine Interfaces

We use Weighted Finite-State Transducers (WFSTs) to represent the different sources of information available: the initial hypotheses, the possible errors, the constraints imposed by the task (interaction language) and the user input. The fusion of these models to find the most probable output string can be performed efficiently by using carefully selected transducer operations. The proposed system initially suggests an output based on the set of hypotheses, possible errors and Constraint Models. Then, if human intervention is needed, a multimodal approach, where the user input is combined with the aforementioned models, is applied to produce, with a minimum user effort, the desired output. This approach offers the practical advantages of a de-coupled model (e.g. input-system + parameterized rules + post-processor), keeping at the same time the error-recovery power of an integrated approach, where all the steps of the process are performed in the same formal machine (as in a typical HMM in speech recognition) to avoid that an error at a given step remains unrecoverable in the subsequent steps. After a presentation of the theoretical basis of the proposed multi-source information system, its application to two real world problems, as an example of the possibilities of this architecture, is addressed. The experimental results obtained demonstrate that a significant user effort can be saved when using the proposed procedure. A simple demonstration, to better understand and evaluate the proposed system, is available on the web https://demos.iti.upv.es/hi/. (C) 2015 Elsevier B.V. All rights reserved.Navarro Cerdan, JR.; Llobet Azpitarte, R.; Arlandis, J.; Perez-Cortes, J. (2016). Composition of Constraint, Hypothesis and Error Models to improve interaction in Human-Machine Interfaces. Information Fusion. 29:1-13. doi:10.1016/j.inffus.2015.09.001S1132

Asymptotic bounds for the sizes of constant dimension codes and an improved lower bound

We study asymptotic lower and upper bounds for the sizes of constant dimension codes with respect to the subspace or injection distance, which is used in random linear network coding. In this context we review known upper bounds and show relations between them. A slightly improved version of the so-called linkage construction is presented which is e.g. used to construct constant dimension codes with subspace distance $d=4$, dimension $k=3$ of the codewords for all field sizes $q$, and sufficiently large dimensions $v$ of the ambient space, that exceed the MRD bound, for codes containing a lifted MRD code, by Etzion and Silberstein.Comment: 30 pages, 3 table

An adaptive version of k-medoids to deal with the uncertainty in clustering heterogeneous data using an intermediary fusion approach

This paper introduces Hk-medoids, a modified version of the standard k-medoids algorithm. The modification extends the algorithm for the problem of clustering complex heterogeneous objects that are described by a diversity of data types, e.g. text, images, structured data and time series. We first proposed an intermediary fusion approach to calculate fused similarities between objects, SMF, taking into account the similarities between the component elements of the objects using appropriate similarity measures. The fused approach entails uncertainty for incomplete objects or for objects which have diverging distances according to the different component. Our implementation of Hk-medoids proposed here works with the fused distances and deals with the uncertainty in the fusion process. We experimentally evaluate the potential of our proposed algorithm using five datasets with different combinations of data types that define the objects. Our results show the feasibility of the our algorithm, and also they show a performance enhancement when comparing to the application of the original SMF approach in combination with a standard k-medoids that does not take uncertainty into account. In addition, from a theoretical point of view, our proposed algorithm has lower computation complexity than the popular PAM implementation

Microarray analysis revealed different gene expression patterns in HepG2 cells treated with low and high concentrations of the extracts of Anacardium occidentale shoots

In this study, the effects of low and high concentrations of the Anacardium occidentale shoot extracts on gene expression in liver HepG2 cells were investigated. From MTT assays, the concentration of the shoot extracts that maintained 50% cell viability (IC50) was 1.7 mg/ml. Cell viability was kept above 90% at both 0.4 mg/ml and 0.6 mg/ml of the extracts. The three concentrations were subsequently used for the gene expression analysis using Affymetrix Human Genome 1.0 S.T arrays. The microarray data were validated using real-time qRT–PCR. A total of 246, 696 and 4503 genes were significantly regulated (P < 0.01) by at least 1.5-fold in response to 0.4, 0.6 and 1.7 mg/ml of the extracts, respectively. Mutually regulated genes in response to the three concentrations included CDKN3, LOC100289612, DHFR, VRK1, CDC6, AURKB and GABRE. Genes like CYP24A1, BRCA1, AURKA, CDC2, CDK2, CDK4 and INSR were significantly regulated at 0.6 mg/ml and 1.7 mg but not at 0.4 mg/ml. However, the expression of genes including LGR5, IGFBP3, RB1, IDE, LDLR, MTTP, APOB, MTIX, SOD2 and SOD3 were exclusively regulated at the IC50 concentration. In conclusion, low concentrations of the extracts were able to significantly regulate a sizable number of genes. The type of genes that were expressed was highly dependent on the concentration of the extracts used

Mechanisms and treatment of ischaemic stroke: insights from genetic associations

The precise pathophysiology of ischaemic stroke is unclear, and a greater understanding of the different mechanisms that underlie large-artery, cardioembolic and lacunar ischaemic stroke subtypes would enable the development of more-effective, subtype-specific therapies. Genome-wide association studies (GWASs) are identifying novel genetic variants that associate with the risk of stroke. These associations provide insight into the pathophysiological mechanisms, and present opportunities for novel therapeutic approaches. In this Review, we summarize the genetic variants that have been linked to ischaemic stroke in GWASs to date and discuss the implications of these associations for both our understanding and treatment of ischaemic stroke. The majority of genetic variants identified are associated with specific subtypes of ischaemic stroke, implying that these subtypes have distinct genetic architectures and pathophysiological mechanisms. The findings from the GWASs highlight the need to consider whether therapies should be subtype-specific. Further GWASs that include large cohorts are likely to provide further insights, and emerging technologies will complement and build on the GWAS findings