Definition of a serum marker panel for glioblastoma discrimination and identification of Interleukin 1 beta in the microglial secretome as a novel mediator of endothelial cell survival induced by C-reactive protein

Glioblastoma (GBM) is the most common malignant adult primary brain tumor. We profiled 724 cancer-associated proteins in sera of healthy individuals (n = 27) and GBM (n = 28) using antibody microarray. While 69 proteins exhibited differential abundance in GBM sera, a three-marker panel (LYAM1, BHE40 and CRP) could discriminate GBM sera from that of healthy donors with an accuracy of 89.7% and p < 0.0001. The high abundance of C-reactive protein (CRP) in GBM sera was confirmed in 264 independent samples. High levels of CRP protein was seen in GBM but without a change in transcript levels suggesting a non-tumoral origin. Glioma-secreted Interleukin 6 (IL6) was found to induce hepatocytes to secrete CRP, involving JAK-STAT pathway. The culture supernatant from CRP-treated microglial cells induced endothelial cell survival under nutrient-deprivation condition involving CRP-Fc gamma RIII signaling cascade. Transcript profiling of CRP-treated microglial cells identified Interleukin 1 beta (IL1 beta) present in the microglial secretome as the key mediator of CRP-induced endothelial cell survival. IL1 beta neutralization by antibody-binding or siRNA-mediated silencing in microglial cells reduced the ability of the supernatant from CRP-treated microglial cells to induce endothelial cell survival. Thus our study identifies a serum based three-marker panel for GBM diagnosis and provides leads for developing targeted therapies. Biological significance A complex antibody microarray based serum marker profiling identified a three-marker panel - LYAM1, BHE40 and CRP as an accurate discriminator of glioblastoma sera from that of healthy individuals. CRP protein is seen in high levels without a concomitant increase of CRP transcripts in glioblastoma. Glioma-secreted IL6 induced hepatocytes to produce CRP in a JAK-STAT signaling dependent manner. CRP induced microglial cells to release IL1 beta which in turn promoted endothelial cell survival. This study, besides defining a serum panel for glioblastoma discrimination, identified IL1 beta as a potential candidate for developing targeted therapy. (C) 2015 Elsevier B.V. All rights reserved.

Electric field and temperature dependence of the local structural disorder in the lead-free ferroelectric Na0.5Bi0.5TiO3: An EXAFS study

The complex nature of the structural disorder in the lead-free ferroelectric Na1/2Bi1/2TiO3 has a profound impact on the perceived global structure and polar properties. In this paper, we have investigated the effect of electric field and temperature on the local structure around theBi and Ti atoms using extended x-ray absorption fine structure. Detailed analysis revealed that poling brings about a noticeable change in the bond distances associated with the Bi-coordination sphere, whereas the Ti coordination remains unaffected. We also observed discontinuity in the Bi-O bond lengths across the depolarization temperature of the poled specimen. These results establish that the disappearance of the monoclinic-like (Cc) global distortion, along with the drastic suppression of the short-ranged in-phase octahedral tilt after poling B. N. Rao et al., Phys. Rev. B 88, 224103 (2013)] is a result of the readjustment of theA-O bonds by the electric field, so as to be in conformity with the rhombohedral R3c structure.

Order-disorder phase transition and multiferroic behaviour in a metal organic framework compound (CH3)(2)NH2Co(HCOO)(3)

We have investigated the multiferroic and glassy behaviour of metal-organic framework (MOF) material (CH3)(2)NH2Co(CHOO)(3). The compound has perovskite-like architecture in which the metal-formate forms a framework. The organic cation (CH3)(2)NH2+ occupies the cavities in the formate framework in the framework via N-H center dot center dot center dot O hydrogen bonds. At room temperature, the organic cation is disordered and occupies three crystallographically equivalent positions. Upon cooling, the organic cation is ordered which leads to a structural phase transition at 155 K. The structural phase transition is associated with a para-ferroelectric phase transition and is revealed by dielectric and pyroelectric measurements. Further, a PE hysteresis loop below 155 K confirms the ferroelectric behaviour of the material. Analysis of dielectric data reveal large frequency dispersion in the values of dielectric constant and tan delta which signifies the presence of glassy dielectric behaviour. The material displays a antiferromagnetic ordering below 15 K which is attributed to the super-exchange interaction between Co2+ ions mediated via formate linkers. Interestingly, another magnetic transition is also found around 11 K. The peak of the transition shifts to lower temperature with increasing frequency, suggesting glassy magnetism in the sample. (C) 2016 AIP Publishing LLC.

Effect of applied pressure on densification of monolithic ZrCx ceramic by reactive hot pressing

The effect of applied pressure on reactive hot pressing (RHP) of zirconium (Zr):graphite (C) in molar ratios of 1:0.5, 1:0.67, 1:0.8, and 1:1 was studied at 1200 degrees C for 60 min. The relative density achievable increased with increasing pressure and ranged from 99% at 4 MPa for ZrC0.5 to 93% for stoichiometric ZrC at 100 MPa. The diminishing influence of pressure on the final density with increasing stoichiometry is attributed to two causes: the decreasing initial volume fraction of the plastically deforming Zr metal which leads to the earlier formation of a contiguous, stress shielding carbide skeleton and the larger molar volume shrinkage during reaction which leads to pore formation in the final stages. A numerical model of the creep densification of a dynamically evolving microstructure predicts densities that are consistent with observations and confirm that the availability of a soft metal is primarily responsible for the achievement of such elevated densification during RHP. The ability to densify nonstoichiometric compositions like ZrC0.5 at pressures as low as 4 MPa offers an alternate route to fabricating dense nonstoichiometric carbides.

Effective thermal conductivity of reactive packed beds of hydriding materials

Applications of hydriding materials for solid state hydrogen storage, hydrogen compression, thermal energy storage and sorption heating and cooling systems have been demonstrated successfully. However, the performance of these devices significantly depends upon heat and mass transfer characteristics of the reactive packed beds. One of the important parameters regulating heat and mass transfer in the hydriding bed is its effective thermal conductivity (ETC), which is dependent on several operating parameters such as pressure and temperature. ETC also varies significantly due to the variation of hydrogen concentration during the hydriding and dehydriding processes. Based on the extensive studies done by the authors on ETC of metal hydride beds, a review of experimental methods, mathematical studies and augmentation techniques is presented in this paper, with emphasis on the effects of operating parameters on ETC. (C) 2016 Elsevier Ltd. All rights reserved.

Arc Root Attachment on the Anode Surface of Arc Plasma Torch Observed with a Novel Method

The arc-root attachment on the anode surface of a dc non-transferred arc plasma torch has been successfully observed using a novel approach. A specially designed copper mirror with a boron nitride film coated on its surface central-region is employed to avoid the effect of intensive light emitted from the arc column upon the observation of weakly luminous arc root. It is found that the arc-root attachment is diffusive on the anode surface of the argon plasma torch, while constricted arc roots often occur when hydrogen or nitrogen is added into argon as the plasma-forming gas.

Mapping Closure Approximation for Reactive Scalars in Random Flows

The Mapping Closure Approximation (MCA) approach is developed to describe the statistics of both conserved and reactive scalars in random flows. The statistics include Probability Density Function (PDF), Conditional Dissipation Rate (CDR) and Conditional Laplacian (CL). The statistical quantities are calculated using the MCA and compared with the results of the Direct Numerical Simulation (DNS). The results obtained from the MCA are in agreement with those from the DNS. It is shown that the MCA approach can predict the statistics of reactive scalars in random flows.

Surface attachment of protein fibrils via covalent modification strategies.

Chemical control of surface functionality and topography is an essential requirement for many technological purposes. In particular, the covalent attachment of monomeric proteins to surfaces has been the object of intense studies in recent years, for applications as varied as electrochemistry, immuno-sensing, and the production of biocompatible coatings. Little is known, however, about the characteristics and requirements underlying surface attachment of supramolecular protein nanostructures. Amyloid fibrils formed by the self-assembly of peptide and protein molecules represent one important class of such structures. These highly organized beta-sheet-rich assemblies are a hallmark of a range of neurodegenerative disorders, including Alzheimer's disease and type II diabetes, but recent findings suggest that they have much broader significance, potentially representing the global free energy minima of the energy landscapes of proteins and having potential applications in material science. In this paper, we describe strategies for attaching amyloid fibrils formed from different proteins to gold surfaces under different solution conditions. Our methods involve the reaction of sulfur containing small molecules (cystamine and 2-iminothiolane) with the amyloid fibrils, enabling their covalent linkage to gold surfaces. We demonstrate that irreversible attachment using these approaches makes possible quantitative analysis of experiments using biosensor techniques, such as quartz crystal microbalance (QCM) assays that are revolutionizing our understanding of the mechanisms of amyloid growth and the factors that determine its kinetic behavior. Moreover, our results shed light on the nature and relative importance of covalent versus noncovalent forces acting on protein superstructures at metal surfaces.

Nature of disorder and localization in amorphous carbon

The electronic structure of amorphous diamond-like carbon is studied. Analysis of the participation ratio shows that π states within the σ-σ* gap are localized. The localization arises from dihedral angle disorder. The localization of π states causes the mobility gap to exceed the optical gap, which accounts for the low carrier mobility and the flat photoluminesence excitation spectrum. © 1998 Elsevier Science B.V. All rights reserved.

UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development

It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional DSD team acts as the first point of contact. The underlying pathophysiology of DSD and the strengths and weaknesses of the tests that can be performed should be discussed with the parents and affected young person and tests undertaken in a timely fashion. This clinician should be part of a multidisciplinary team experienced in management of DSD and should ensure that the affected person and parents are as fully informed as possible and have access to specialist psychological support. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration. © 2011 Blackwell Publishing Ltd.

Statistical analysis of synthetic earthquake catalogs generated by models with various levels of fault zone disorder

The stress release model, a stochastic version of the elastic rebound theory, is applied to the large events from four synthetic earthquake catalogs generated by models with various levels of disorder in distribution of fault zone strength (Ben-Zion, 1996) They include models with uniform properties (U), a Parkfield-type asperity (A), fractal brittle properties (F), and multi-size-scale heterogeneities (M). The results show that the degree of regularity or predictability in the assumed fault properties, based on both the Akaike information criterion and simulations, follows the order U, F, A, and M, which is in good agreement with that obtained by pattern recognition techniques applied to the full set of synthetic data. Data simulated from the best fitting stress release models reproduce, both visually and in distributional terms, the main features of the original catalogs. The differences in character and the quality of prediction between the four cases are shown to be dependent on two main aspects: the parameter controlling the sensitivity to departures from the mean stress level and the frequency-magnitude distribution, which differs substantially between the four cases. In particular, it is shown that the predictability of the data is strongly affected by the form of frequency-magnitude distribution, being greatly reduced if a pure Gutenburg-Richter form is assumed to hold out to high magnitudes.