The Neurotrophin Receptor TrkC as a Novel Molecular Target of the Antineuroblastoma Action of Valproic Acid

Neurotrophins and their receptors are relevant factors in controlling neuroblastoma growth and progression. The histone deacetylase (HDAC) inhibitor valproic acid (VPA) has been shown to downregulate TrkB and upregulate the p75NTR/sortilin receptor complex. In the present study, we investigated the VPA effect on the expression of the neurotrophin-3 (NT-3) receptor TrkC, a favorable prognostic marker of neuroblastoma. We found that VPA induced the expression of both full-length and truncated (TrkC-T1) isoforms of TrkC in human neuroblastoma cell lines without (SH-SY5Y) and with (Kelly, BE(2)-C and IMR 32) MYCN amplification. VPA enhanced cell surface expression of the receptor and increased Akt and ERK1/2 activation by NT-3. The HDAC inhibitors entinostat, romidepsin and vorinostat also increased TrkC in SH-SY5Y, Kelly and BE(2)-C but not IMR 32 cells. TrkC upregulation by VPA involved induction of RUNX3, stimulation of ERK1/2 and JNK, and ERK1/2-mediated Egr1 expression. In SH-SY5Y cell monolayers and spheroids the exposure to NT-3 enhanced the apoptotic cascade triggered by VPA. Gene silencing of both TrkC-T1 and p75NTR prevented the NT-3 proapoptotic effect. Moreover, NT-3 enhanced p75NTR/TrkC-T1 co-immunoprecipitation. The results indicate that VPA upregulates TrkC by activating epigenetic mechanisms and signaling pathways, and sensitizes neuroblastoma cells to NT-3-induced apoptosis.      

Separation of the Fatty Acids in Menhaden Oil as Methyl Esters with a Highly Polar Ionic Liquid Gas Chromatographic Column and Identification by Time of Flight Mass spectrometry

The fatty acids contained in marine oils or products are traditionally analyzed by gas chromatography using capillary columns coated with polyethylene glycol phases. Recent reports indicate that 100 % cyanopropyl siloxane phases should also be used when the analyzed samples contain trans fatty acids. We investigated the separation of the fatty acid methyl esters prepared from menhaden oil using the more polar SLB-IL111 (200 m × 0.25 mm) ionic liquid capillary column and the chromatographic conditions previously optimized for the separation of the complex mixture of fatty acid methyl esters prepared from milk fat. Identifications of fatty acids were achieved by applying Ag⁺-HPLC fractionation and GC-TOF/MS analysis in CI⁺ mode with isobutane as the ionization reagent. Calculation of equivalent chain lengths confirmed the assignment of double bond positions. This methodology allowed the identification of 125 fatty acids in menhaden oil, including isoprenoid and furanoid fatty acids, and the novel 7-methyl-6-hexadecenoic and 7-methyl-6-octadecenoic fatty acids. The chromatographic conditions applied in this study showed the potential of separating in a single 90-min analysis, among others, the short chain and trans fatty acids contained in dairy products, and the polyunsaturated fatty acids contained in marine products.     

Mechanical refrigeration using an ejector-injector to transfer the working fluid from the evaporator to the condenser

The refrigeration plant described in this paper uses an ejector-injector instead of a compressor to pump the freezing mixture from the evaporator to the condenser. A pump draws the liquid from the condenser and pumps it to another vessel. Before the ejector-injector, a heat exchanger preheats the refrigerating fluid to speed up the mixing with steam ejected from the evaporator. The steam is compressed using kinetic energy in the ejector-injector and the pump supplies a discharge pressure to operate the plant. The heat transfer fluid, the condensing and evaporating pressures and the energy losses determine the operating features of the plant. Energy saving is obtained using such an ejector-injector and it provides a simple method of refrigeration. The operating conditions were optimized in this study and the feasibility of the plant was confirmed.     

P systems with symport/antiport simulating counter automata

The generative capability of several variants of P systems with symport/antiport is studied via the simulation of counter automata. This leads to the reduction of the complexity, expressed in number of membranes and weight of rules, of P systems generating recursively enumerable sets.Received: 4 December 2003, Published online: 3 November 2004     

On-line hollow-fiber flow field-flow fractionation-electrospray ionization/time-of-flight mass spectrometry of intact proteins

Capabilities of mass spectrometry for the analysis of intact proteins can be increased through separation methods. Flow field-flow fractionation (FlFFF) is characterized by the particularly "soft" separation mechanism, which is ideally suited to maintain the native structure of intact proteins. This work describes the original on-line coupling between hollow-fiber FlFFF (HF FlFFF), the microcolumn variant of FlFFF, and electrospray ionization/time-of-flight mass spectrometry (ESI/TOFMS) for the analysis and characterization of intact proteins. The results show that the native (or pseudonative) structure of horse heart myoglobin and horseradish peroxidase is maintained. Sample desalting is also observed for horse heart myoglobin. Correlation between the molar mass values independently measured by HF FlFFF retention and ESI/TOFMS allows us to confirm the protein aggregation features of bovine serum albumin and to indicate possible changes in the quaternary structure of human hemoglobin.     

Market research for requirements analysis using linguistic tools

Numerous studies in recent months have proposed the use of linguistic instruments to support requirements analysis. There are two main reasons for this: (i) the progress made in natural language processing and (ii) the need to provide the developers of software systems with support in the early phases of requirements definition and conceptual modelling. This paper presents the results of an online market research intended (a) to assess the economic advantages of developing a CASE (computer-aided software engineering) tool that integrates linguistic analysis techniques for documents written in natural language, and (b) to verify the existence of the potential demand for such a tool. The research included a study of the language – ranging from completely natural to highly restricted – used in documents available for requirements analysis, an important factor given that on a technological level there is a trade-off between the language used and the performance of the linguistic instruments. To determine the potential demand for such tool, some of the survey questions dealt with the adoption of development methodologies and consequently with models and support tools; other questions referred to activities deemed critical by the companies involved. Through statistical correspondence analysis of the responses, we were able to outline two profiles of companies that correspond to two potential market niches, which are characterised by their very different approach to software development.

Interaction of interface delamination and plasticity in tensile steel members reinforced by CFRP plates

This paper presents experimental and numerical results related to double shear lap tests performed on steel specimens reinforced using CFRP plates. These tests have been simulated taking into account the elastic–plastic behavior of the steel and the delamination between steel and CFRP by means of a cohesive approach. The results obtained are discussed in terms of: (i) maximum load bearing capacity, (ii) minimum bond length in order to exploit the maximum load bearing capacity, (iii) brittle to ductile transition of the interface failure (iv) combination of interface delamination and plastic deformation of the steel. Design formulas for the definition of the minimum bond length and the load bearing capacity of the joint are validated.     

Planar Motion Estimation and Linear Ground Plane Rectification using an Uncalibrated Generic Camera

We address and solve the self-calibration of a generic camera that performs planar motion while viewing (part of) a ground plane. Concretely, assuming initial sets of correspondences between several images of the ground plane as known, we are interested in determining both the camera motion and the geometry of the ground plane. The latter is obtained through the rectification of the image of the ground plane, which gives a bijective correspondence between pixels and points on the ground plane.     

SERVICES,SEMANTICS, AND STANDARDS: ELEMENTS OF A LEARNING GRID INFRASTRUCTURE

There has been considerable political pressure and much hope invested in the use of communication and information technologies to provide wider access to education, while improving quality and reducing costs. Unfortunately, many of the responses to the challenge of these aspirations have consisted of simple Web technology-driven products, which have failed to progress effective learning. In this paper we outline the characteristics and pedagogical goals of a learning paradigm that is used to drive the technical requirements, rather than being constrained by what is easily achieved in XHTML. We identify and explain the key roles played by services, semantics, and standards in meeting pedagogical goals of novel learning situations, and illustrate with some scenarios that build bridges between traditional learning contexts and future possibilities. Crucially, we explain why we have adopted Grid technologies in the European Learning Grid Infrastructure (ELeGI) research program.     

Optimal wind turbines placement within a distribution market environment

This paper proposes a hybrid optimization method for optimal allocation of wind turbines (WTs) that combines genetic algorithm (GA) and market-based optimal power flow (OPF). The method jointly maximizes net present value (NPV) related to WTs investment made by WTs’ developers and social welfare (SW) considering different combinations of wind generation and load demand over a year. The GA is used to choose the optimal size while the market-based OPF to determine the optimal number of WTs at each candidate bus. The stochastic nature of both load demand and wind power generation is modeled by hourly time series analysis. The effectiveness of the method is demonstrated with an 84-bus 11.4 kV radial distribution system.