Pediatric Brain Tumors: Signatures from the Intact Proteome

The present investigation aimed to explore the intact proteome of tissues of pediatric brain tumors of different WHO grades and localizations, including medulloblastoma, pilocytic astrocytoma, and glioblastoma, in comparison with the available data on ependymoma, to contribute to the understanding of the molecular mechanisms underlying the onset and progression of these pathologies. Tissues have been homogenized in acidic water–acetonitrile solutions containing proteases inhibitors and analyzed by LC–high resolution MS for proteomic characterization and label-free relative quantitation. Tandem MS spectra have been analyzed by either manual inspection or software elaboration, followed by experimental/theoretical MS fragmentation data comparison by bioinformatic tools. Statistically significant differences in protein/peptide levels between the different tumor histotypes have been evaluated by ANOVA test and Tukey’s post-hoc test, considering a p-value > 0.05 as significant. Together with intact protein and peptide chains, in the range of molecular mass of 1.3–22.8 kDa, several naturally occurring fragments from major proteins, peptides, and proteoforms have been also identified, some exhibiting proper biological activities. Protein and peptide sequencing allowed for the identification of different post-translational modifications, with acetylations, oxidations, citrullinations, deamidations, and C-terminal truncations being the most frequently characterized. C-terminal truncations, lacking from two to four amino acid residues, particularly characterizing the β-thymosin peptides and ubiquitin, showed a different modulation in the diverse tumors studied. With respect to the other tumors, medulloblastoma, the most frequent malignant brain tumor of the pediatric age, was characterized by higher levels of thymosin β4 and β10 peptides, the latter and its des-IS form particularly marking this histotype. The distribution pattern of the C-terminal truncated forms was also different in glioblastoma, particularly underlying gender differences, according to the definition of male and female glioblastoma as biologically distinct diseases. Glioblastoma was also distinguished for the peculiar identification of the truncated form of the α-hemoglobin chain, lacking the C-terminal arginine, and exhibiting oxygen-binding and vasoconstrictive properties different from the intact form. The proteomic characterization of the undigested proteome, following the top-down approach, was challenging to originally investigate the post-translational events that differently characterize pediatric brain tumors. This study provides a contribution to elucidate the molecular profiles of the solid tumors most frequently affecting the pediatric age, and which are characterized by different grades of aggressiveness and localization.     

Technological and organizational change in the Brazilian computer industry: A case study

Abstract

This article gives an account of the results of a case study undertaken at a pioneer and particularly prominent firm in the Brazilian computer industry: COBRA — Computadores e Sistemas Brasileiros SA.

The study is part of a research project¹ whose main goal is the identification of viable organizational and technological options that could enhance the performance of firms in the Brazilian electro‐electronics industry. Among the more important findings, it was observed that the firm has the potential to evolve to a more flexible structure, in keeping with the new requirements of the probable future market scenarios within its sector.

Everything indicated, however, that the main constraining factors for bringing about such a structure were connected with the firm's culture and beliefs and with the indirect influence of the National Policy of Information Technology upon these. An hypothesis was put forward for an organizational model, and the necessary supportive computerized technology, which could be particularly appropriate in view of the impending deregulation, of the Brazilian computer industry. Also, in the scope of the current discussion on the restructuring of this industry in terms of a greater concentration, an alternative to the prevailing school of thought was proposed, and for whose success the organizational model at issue purports to be particularly relevant.     

Phosphorus‐containing poly(ester‐imide)–polydimethylsiloxane copolymers

New phosphorus‐containing poly(ester‐imide)‐polydimethylsiloxane copolymers were prepared by solution polycondensation of 1,4‐[2‐(6‐oxido‐6H‐dibenz < c,e > < 1, 2 > oxaphosphorin‐6‐yl)]naphthalene‐bis(trimellitate) dianhydride with a mixture of an aromatic diamine (1,3‐bis(4‐aminophenoxy)benzene) and α,ω‐bis(3‐aminopropyl)oligodimethylsiloxane of controlled molecular weight, in various ratios. Poly(amic acid) intermediates were converted quantitatively to the corresponding polyimide structures using a solution imidization procedure. The polymers are easily soluble in polar organic solvents, such as N‐methyl‐2‐pyrrolidone and N,N‐dimethylformamide, as well as in less polar solvents such as tetrahydrofuran. They show good thermal stability, the decomposition temperature being above 370 °C. The glass transition temperatures are in the range 165–216 °C. Solutions of the polymers in N‐methyl‐2‐pyrrolidone exhibit photoluminescence in the blue region. Copyright © 2010 Society of Chemical Industry     

Antiviral activity of donkey milk protein fractions on echovirus type 5

Antiviral activity of Ragusano donkeys' milk proteins was investigated for the effect on echovirus type 5, known to infect the gastrointestinal tract of humans. Three protein fractions were tested; casein (CN), whey protein (WP) and a low molecular whey protein fraction (LWP; <30,000 Da). The antiviral activity of WP and LWP was tested on echovirus type 5 at three concentrations (1, 5 and 10 mg mL^?1); CN was assessed only at the lower concentration. All donkey milk protein fractions showed significant inhibition on virus replication at the concentration of 1 mg mL^?1, and both WP and LWP fractions showed significant inhibition on the virus replication at all concentrations tested. The strongest antiviral effect was observed for the WP fraction. These findings show that the different whey proteins in donkey milk, probably acting in synergy, exert antiviral activity on echovirus 5 and might contribute to prevent gastrointestinal virus infections in humans.     

Assessment of bottom-up sectoral and regional mitigation potentials

The greenhouse gas mitigation potential of different economic sectors in three world regions are estimated using a bottom-up approach. These estimates provide updates of the numbers reported in the Fourth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR4). This study is part of a larger project aimed at comparing greenhouse gas mitigation potentials from bottom-up and top-down approaches. The sectors included in the analysis are energy supply, transport, industry and the residential and service sector. The mitigation potentials range from 11 to 15 GtCO₂eq. This is 26–38% of the baseline in 2030 and 47–68% relative to the year 2000. Potential savings are estimated for different cost levels. The total potential at negative costs is estimated at 5–8% relative to the baseline, with the largest share in the residential and service sector and the highest reduction percentage for the transport and industry sectors. These (negative) costs include investment, operation and maintenance and fuel costs and revenues at moderate discount rates of 3–10%. At costs below 100 US$/tCO₂, the largest potential reductions in absolute terms are estimated in the energy supply sector, while the transport sector has the lowest reduction potential.     

A soft‐cache strategy for pathologist's navigation in virtual microscopy

Navigation through large microscopical images demands special characteristics like flexibility to access image data and progressive recovery or relevant information, i.e., several qualities, magnifications, and random accesses to any desired Window of Interest in the Virtual Slide (VS). Nowadays there exist systems that allow such interaction, but with a certain delay, which is dependent on the application. It has been shown that caching or prefetching policies can speed up interaction with these systems. This article presents an optimal soft‐cache strategy, which improves the navigation times in virtual microscopy. The entire method includes an optimal soft‐cache strategy and a dynamical probabilistic model of a pathologist's navigation. This strategy was implemented as a Client‐Server application, using the JPEG2000‐JPIP standard and evaluated using different navigation patterns, namely, four different pathologists exploring 10 VS, stained with different dyes. The present approach was compared with a conventional soft‐cache method and the cache performance improved, in average, in about a 10%. Microsc. Res. Tech., 2011. © 2010 Wiley‐Liss, Inc.     

Analytical model for Binding Refresh Request to reduce storage and communication overhead in MIPv6 network

Home agent is a key component of MIPv6 functionality that comprises binding cache to hold the mobile nodes current point of attachment to the Internet. This paper is concerned with binding cache support for home agents within MIPv6 network. Existing binding cache of home agent supports weak cache consistency by using fixed contract length for Binding Refresh Request, which functions reasonably well in normal situations. However, maintaining a strong binding cache consistency in home agent as a crucial exceptional handling mechanism has become more demanding for the following objectives: (i) to adapt increasingly frequent change of care‐of address due to mobile nodes movement detection update; (ii) to provide fine‐grain controls to balance the binding cache load distributions for better delivery services; and (iii) to reduce the overhead allowances around the binding cache. In this paper, we have first verified the effectiveness of Binding Refresh Request contract length, and on the basis of that, two dynamic contract algorithms are suggested to reduce the storage and communication overhead allowances in binding cache. We have also compared our technique with the existing fixed Binding Refresh Request contract length, and our simulation results reveals that the proposed approach provides an effective performance to reduce overhead within the network. Copyright © 2014 John Wiley & Sons, Ltd.