A great challenge to clinical development is the delivery of chemotherapeutic agents, known to cause severe toxic effects, directly to diseased sites which increase the therapeutic index whilst minimizing off-target side effects. Antibody-conjugated nanoparticles offer great opportunities to overcome these limitations in therapeutics. They combine the advantages given by the nanoparticles with the ability to bind to their target with high affinity and improve cell penetration given by the antibodies. This specialized vehicle, that can encapsulate several chemotherapeutic agents, can be engineered to possess the desirable properties, allowing overcoming the successive physiological conditions and to cross biological barriers and reach a specific tissue or cell. Moreover, antibody-conjugated nanoparticles have shown the ability to be internalized through receptor-mediated endocytosis and accumulate in cells without being recognized by the P-glycoprotein, one of the main mediators of multi-drug resistance, resulting in an increase in the intracellular concentration of drugs. Also, progress in antibody engineering has allowed the manipulation of the basic antibody structure for raising and tailoring specificity and functionality. This review explores recent developments on active drug targeting by nanoparticles functionalized with monoclonal antibodies (polymeric micelles, liposomes and polymeric nanoparticles) and summarizes the opportunities of these targeting strategies in the therapy of serious diseases (cancer, inflammatory diseases, infectious diseases, and thrombosis).

Chitosan-based monoliths activated by plasma technology induced the coupling of a robust biomimetic ligand, previously reported as an artificial Protein A, with high yields while minimizing the environmental impact of the procedure. Due to the high porosity, good mechanical and tunable physicochemical properties of the affinity chitosan-based monoliths, it is possible to achieve high binding capacities (150 ± 10 mg antibody per gram support), and to recover 90 ± 5% of the bound protein with 98% purity directly from cell-culture extracts. Therefore, the chitosan-based monoliths prepared by clean processes exhibit a remarkable performance for the one-step capture and recovery of pure antibodies or other biological molecules with biopharmaceutical relevance.

Technology assessment is essentially an approach, a collective of the systematic methods used to scientifically investigate the conditions for and the consequences of technology and technicising and to denote their societal evaluation. It is an investigation about the technological developments as well as an evaluation of its potential impacts on society. The assessment of emerging technologies, however, requires special attention. Brain-Computer Interface (BCI) is an emerging technology which allows for the direct communication between the brain and an external device. It is a truly direct connection, with no use of the normal output pathways of peripheral nerves and muscles, allowing for the brain to have control over objects and software without intermediates. To address these kinds of technologies at early stages of development, Constructive Technology Assessment (CTA), a member of Technology Assessment approaches, has been considered as one of the most fitting approaches. As an emerging technology, BCI is at its early stages of research and thus many challenges are still ahead. Mainstream adoption is not expected in least 10 years many challenges are yet to be overcome. Therefore, the objective of this article is to discuss and present a methodological approach to assess brain-computer interface technology considering constructive technology assessment and future oriented technology analysis as the main processes to undertake the assessment. The assessment will focus only on the non-invasive type of BCI and for medical applications in three defined areas: Communication & Control, Motor Substitution and Motor Recovery for a time horizon of 10 years, 2022. These areas were chosen based on the capability of BCI to serve as a replacement of normal neuromuscular pathways. That makes it one of the best technologies to help people in activating and controlling assistive technologies which enable communication and control of the environment. However, the real impacts of BCI will depend directly on the development of competing technologies, and also on the improvement in BCI research. Only then, the potential applications and end users could grow dramatically.

Object-oriented programming languages presently are the dominant paradigm of application development (e.g., Java, .NET). Lately, increasingly more Java applications have long (or very long) execution times and manipulate large amounts of data/information, gaining relevance in fields related with e-Science (with Grid and Cloud computing). Significant examples include Chemistry, Computational Biology and Bio-informatics, with many available Java-based APIs (e.g., Neobio).Often, when the execution of such an application is terminated abruptly because of a failure (regardless of the cause being a hardware of software fault, lack of available resources, etc.), all of its work already performed is simply lost, and when the application is later re-initiated, it has to restart all its work from scratch, wasting resources and time, while also being prone to another failure and may delay its completion with no deadline guarantees.Our proposed solution to address these issues is through incorporating mechanisms for checkpointing and migration in a JVM. These make applications more robust and flexible by being able to move to other nodes, without any intervention from the programmer. This article provides a solution to Java applications with long execution times, by extending a JVM (Jikes research virtual machine) with such mechanisms. Copyright © 2011 John Wiley & Sons, Ltd.

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The article presents a review of the use of cross-section and staining techniques for investigating natural organic materials (mainly proteinaceous and oil-based binders/varnishes) in painted and polychrome artworks, considering the requirements of conservation practice and routine diagnostics. The reviewed literature calls attention to the importance of using cross sections to prepare samples for optical microscopy and to different properties of embedding resins; the most appropriate instrumental conditions for optical microscopy; and the advantages and disadvantages of the most common staining techniques. A few case studies were selected to illustrate the use of autofluorescence (intrinsic fluorescence) and induced fluorescence (using specific staining tests and fluorophore-labeled antibodies) for mapping and identifying organic paint materials in cross sections. New directions of research in cross-section analyses and fluorescence-based techniques for the identification and mapping of artistic materials are presented. The complementary use of different stains on the same cross section, further exploration of intrinsic and induced fluorescence of aged versus fresh materials, and applicability of cross-section observation and staining as complementary methods for assessing the effectiveness of restoration treatments, such as cleaning and consolidation, are discussed in the last section of the article.

extran-coated iron oxide magnetic particles modified with ligand 22/8, a protein A mimetic ligand, were prepared and assessed for IgG purification. Dextran was chosen as the agent to modify the surface of magnetic particles by presenting a negligible level of nonspecific adsorption. For the functionalization of the particles with the affinity ligand toward antibodies, three methods have been explored. The optimum coupling method yielded a theoretical maximum capacity for human IgG calculated as 568 ± 33 mg/g and a binding affinity constant of 7.7 × 104 M–1. Regeneration, recycle and reuse of particles was also highly successful for five cycles with minor loss of capacity. Moreover, this support presented specificity and effectiveness for IgG adsorption and elution at pH 11 directly from crude extracts with a final purity of 95% in the eluted fraction.

In this work, we propose RATS, a middleware to enhance and extend the Terracotta framework for Java with the ability to transparently execute multi-threaded Java applications to provide a single-system image. It supports efficient scheduling of threads, according to available resources, across several nodes in a Terracotta cluster, taking advantage of the extra computational and memory resources available. It also supports profiling to gather application characteristics such as dispersion of thread workload, thread inter-arrival time and resource usage of the application. Profiling and clustering capabilities are inserted with the help of byte code instrumentations. We developed a range of alternative scheduling heuristics and classify them based on the application and cluster behavior. The middleware is tested with different applications with varying thread characteristics to assess and classify the scheduling heuristics with respect to application speed-ups. Results indicate that, for a CPU intensive application, it is possible to classify the scheduling heuristic based on application and cluster properties and also achieve linear speed ups. Furthermore, we show that a memory intensive application is able to scale its memory usage considerably when compared to running the application on a single JVM.

Osteosarcoma is the most common primary bone tumor in children and adolescents, with a 5-year disease free survival rate of 70%. Current chemotherapy regimens comprise a group of chemotherapeutic agents in which doxorubicin is included. However, tumor resistance to anthracyclines and cardiotoxicity are limiting factors for its usage. Liposomal formulations of doxorubicin improve its anti-cancer effects but are still insufficient. The research in this area has lead to the production of anthracyclines analogues, such as ladirubicin, the leading compound of alkylcyclines. This new anticancer agent has shown promising results in vivo and in vitro, being effective against osteosarcoma cell lines, including those with a multidrug resistant phenotype. In phase I clinical trials, this molecule caused mild side effects and did not induce significant cardiotoxicity at doses ranging from 1 to 16 mg/m2, resulting in a peak plasma concentration (Cmax) ranging from 0.5 to 1.5 μM. The recommended doses for phase II studies were 12 and 14 mg/m2 in heavily and minimally pretreated/non-pretreated patients, respectively. Phase II clinical trials in ovary, breast, colorectal cancer, NSCLC and malignant melanoma are underway. Given the improved molecular targeting efficacy of these new compounds, ongoing approaches have sought to improve drug delivery systems, to improve treatment efficacy while reducing systemic toxicity. The combination of these two approaches may be a good start for the discovery of new treatment for osteosarcoma.