Morphological and Magnetic Properties of Superparamagnetic Carbon-Coated Fe Nanoparticles Produced by Arc Discharge.

Spherical carbon coated iron particles of nanometric diameter in the 5-10 nm range have been produced by arc discharge at near-atmospheric pressure conditions (using 5-8·10 4 Pa of He). The particles exhibit a crystalline dense iron core with an average diameter 7.4 ± 2.0 nm surrounded by a sealed carbon shell, shown by transmission electron microscopy (TEM), selected-area diffrac- tion (SAED), energy-dispersive X-ray analysis (STEM-EDX) and electron energy loss spectroscopy (EELS). The SAED, EDX and EELS results indicate a lack of traces of core oxidized phases showing an efficient protection role of the carbon shell. The magnetic properties of the nanoparticles have been investigated in the 5-300 K temperature range using a superconducting quantum interference device (SQUID). The results reveal a superparamagnetic behaviour with an average monodomain diameter of 7.6 nm of the nanoparticles. The zero field cooled and field cooled (ZFC-FC)magnetization curves show a blocking temperature (TB)at room temperature very suitable for biomedical applications (drug delivery, magnetic resonance imaging-MRI-, hyperthermia).

An overview of the proposal for a new Package Travel Directive

After an endless wait, a proposal for a new Package Travel Directive repealing Directive 90/314/EEC1 was presented on 9 July 2013 (hereafter, the Proposal).This article is aimed at providing an overall view of the Proposal. I will address the following issues: The concept of traveller; online package holidays and assisted travel arrangements; information requirements; a new particular right of withdrawal for package travel; other changes to the contract before the start of the package; performance of the Package; and insolvency protection. Some early concluding remarks are made as to when a future Package Travel Directive might take place at some future date

In Google we trust?

In a micro-founded model, we derive novel incentives for a monopoly search engine to distort its organic and its sponsored results on searches for online content and offline products. Distorting organic results towards content publishers with less effective display advertising and/or distorting sponsored results towards higher margin merchants (by underweighting consumer relevance in search auctions) increase per capita revenues but lower participation. The interplay of these incentives determines search bias and welfare. We also characterize how the welfare consequences of integration into display advertising, as intermediary or publisher, depend on asymmetries, monopolization and targeting.

Thioflavin-S staining of bacterial inclusion bodies for the fast, simple, and inexpensive screening of amyloid aggregation inhibitors

Amyloid aggregation is linked to a large number of human disorders, from neurodegenerative diseases as Alzheimer"s disease (AD) or spongiform encephalopathies to non-neuropathic localized diseases as type II diabetes and cataracts. Because the formation of insoluble inclusion bodies (IBs) during recombinant protein production in bacteria has been recently shown to share mechanistic features with amyloid self-assembly, bacteria have emerged as a tool to study amyloid aggregation. Herein we present a fast, simple, inexpensive and quantitative method for the screening of potential anti-aggregating drugs. This method is based on monitoring the changes in the binding of thioflavin-S to intracellular IBs in intact Eschericchia coli cells in the presence of small chemical compounds. This in vivo technique fairly recapitulates previous in vitro data. Here we mainly use the Alzheimer"s related beta-amyloid peptide as a model system, but the technique can be easily implemented for screening inhibitors relevant for other conformational diseases simply by changing the recombinant amyloid protein target. Indeed, we show that this methodology can be also applied to the evaluation of inhibitors of the aggregation of tau protein, another amyloidogenic protein with a key role in AD.

Human disease and drug pharmacology, complex as real life

In the past decades drug discovery practice has escaped from the complexity of the formerly used phenotypic screening in animals to focus on assessing drug effects on isolated protein targets in the search for drugs that exclusively and potently hit one selected target, thought to be critical for a given disease, while not affecting at all any other target to avoid the occurrence of side-effects. However, reality does not conform to these expectations, and, conversely, this approach has been concurrent with increased attrition figures in late-stage clinical trials, precisely due to lack of efficacy and safety. In this context, a network biology perspective of human disease and treatment has burst into the drug discovery scenario to bring it back to the consideration of the complexity of living organisms and particularly of the (patho)physiological environment where protein targets are (mal)functioning and where drugs have to exert their restoring action. Under this perspective, it has been found that usually there is not one but several disease-causing genes and, therefore, not one but several relevant protein targets to be hit, which do not work on isolation but in a highly interconnected manner, and that most known drugs are inherently promiscuous. In this light, the rationale behind the currently prevailing single-target-based drug discovery approach might even seem a Utopia, while, conversely, the notion that the complexity of human disease must be tackled with complex polypharmacological therapeutic interventions constitutes a difficult-torefuse argument that is spurring the development of multitarget therapies.

Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates

Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer"s disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multi-target anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.

Thioflavin-S staining of bacterial inclusion bodies for the fast, simple, and inexpensive screening of amyloid aggregation inhibitors

Amyloid aggregation is linked to a large number of human disorders, from neurodegenerative diseases as Alzheimer"s disease (AD) or spongiform encephalopathies to non-neuropathic localized diseases as type II diabetes and cataracts. Because the formation of insoluble inclusion bodies (IBs) during recombinant protein production in bacteria has been recently shown to share mechanistic features with amyloid self-assembly, bacteria have emerged as a tool to study amyloid aggregation. Herein we present a fast, simple, inexpensive and quantitative method for the screening of potential anti-aggregating drugs. This method is based on monitoring the changes in the binding of thioflavin-S to intracellular IBs in intact Eschericchia coli cells in the presence of small chemical compounds. This in vivo technique fairly recapitulates previous in vitro data. Here we mainly use the Alzheimer"s related beta-amyloid peptide as a model system, but the technique can be easily implemented for screening inhibitors relevant for other conformational diseases simply by changing the recombinant amyloid protein target. Indeed, we show that this methodology can be also applied to the evaluation of inhibitors of the aggregation of tau protein, another amyloidogenic protein with a key role in AD.

Low dark count geiger mode avalanche photodiodes fabricated in conventional CMOS technologies

Avalanche photodiodes operated in the Geiger mode present very high intrinsic gain and fast time response, which make the sensor an ideal option for those applications in which detectors with high sensitivity and velocity are required. Moreover, they are compatible with conventional CMOS technologies, allowing sensor and front-end electronics integration within the pixel cell. Despite these excellent qualities, the photodiode suffers from high intrinsic noise, which degrades the performance of the detector and increases the memory area to store the total amount of information generated. In this work, a new front-end circuit that allows low reverse bias overvoltage sensor operation to reduce the noise in Geiger mode avalanche photodiode pixel detectors is presented. The proposed front-end circuit also enables to operate the sensor in the gated acquisition mode to further reduce the noise. Experimental characterization of the fabricated pixel with the conventional HV-AMS 0.35µm technology is also presented in this article.

Targeting striatal metabotropic glutamate receptor type 5 in Parkinson's disease: bridging molecular studies and clinical trials

Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors expressed primarily on neurons and glial cells modulating the effects of glutamatergic neurotransmission. The pharmacological manipulation of these receptors has been postulated to be valuable in the management of some neurological disorders. Accordingly, the targeting of mGlu5 receptors as a therapeutic approach for Parkinson's disease (PD) has been proposed, especially to manage the adverse symptoms associated to chronic treatment with classical PD drugs. Thus, the specific pharmacological blocking of mGlu5 receptors constitutes one of the most attractive non-dopaminergic-based strategies for PD management in general and for the L-DOPA-induced diskynesia (LID) in particular. Overall, we provide here an update of the current state of the art of these mGlu5 receptor-based approaches that are under clinical study as agents devoted to alleviate PD symptoms.

Óleos essenciais no Brasil: aspectos gerais, desenvolvimento e perspectivas

Essential oils are extracted by steam distillation of plants or cold pressing of citrus fruit pericarp. They are used in food, cosmetic, personal care and pharmaceutical industries. In Brazil, oils from orange and related products contribute to near 97% to the positive commercial performance of the sector. Predatory exploitation and the availability of new sources of raw materials, with more attracting prices, changed the paradigm. Prospective studies, sustainable use of Brazilian biodiversity, domestication of exotic species with commercial relevance, the use of breeding techniques and the development of new applications for essential oils are thematic lines, usually multidisciplinary, which have been prompting the expansion of the research on essential oils. This paper presents an analysis on essential oils balance trade from 2005 to 2008 and some historical data on research and production of essential oils in Brazil.

The relationship between first-order capabilities and online innovations. A comparative case study on the publishing sector.

The objective of this thesis was to study the relationship between firstorder capabilities and online innovations. First-order capabilities can be divided into market and technology capabilities, and they play an important role in the production of innovations. The study was carried out in publishing industry, where many changes have taken place in the online environment during the last few years. In the empirical research, four companies were studied, two magazine publishers and two newspaper publishers. The analysis was done in two phases; first every case was analyzed alone and then the cases were compared in cross-case analysis. The most important finding was the positive impact of market capability to the production of online innovations. The study also increased understanding about the relationship between market and technology capabilities and online innovations in general.

Unca Don and Unca Scrooge’s Guide to History. Representations of the Past in the Disney Comics of Don Rosa

This thesis studies the various forms and layers of representations of the past that can be found in the Disney comics of Don Rosa. To stay true to the legacy of renowned comic book artist Carl Barks, Rosa has stopped time in the duck universe to the 1950’s: the decade when Barks created his most noted stories. There is a special feel of historicalness in Rosa’s duck stories, as his characters recall events that occurred in both Rosa’s own stories as well as Barks’. Rosa has shed new light to the past of the characters by writing and illustrating the history of Scrooge McDuck, one of the most beloved Disney characters. Rosa is also adamant that the historical facts used in his stories are always correct and based on thorough research. The methodological tools used in the analysis of the comics come from the fields of comic book studies, film theory, and history culture. Film and comics are recognized by many scholars as very similar media, which share elements that make them comparable in many ways. This thesis utilizes studies on historical film, narrative and genre, which provide valuable insight and comparisons for analysis. The thesis consists of three main chapters, the first of which deconstructs the duck universe in the stories in order to understand how the historicalness in them is created,and which outside elements might affect them, including the genre of Disney comics, publishers, and the legacy of Barks. The next chapter focuses on The Life and Times of Scrooge McDuck series, i.e. the stories which are located in the past. Such stories feature similar representations of history as for example Westerns. They also compress and alter history to meet the restrictions of the medium of comics. The last part focuses on the adventure stories which draw inspiration from for example mythology, and take the characters to strange and mystical, but yet historical worlds. Such treasure-hunting stories show similarity to the action-adventure genre in film and for example their stereotypical representations of foreign cultures. Finally, the chapter addresses the problematic of historical fiction and its capability to write history.

Practical Experiences with Ingesting Materials for Long-Term Preservation

The National Library of Finland is responsible for the collection, preservation and accessibility of Finland’s published national heritage, and for its other unique collections. This presentation will give a general overview of the several processes employed in the digitization and handling of electronic legal deposit. METS format has been chosen as the container format for digitized materials, and considerable amount of effort has been put into creating adequate METS profiles. As METS will be heavily relied as a container format, the practicalities are discussed in some depth. Regarding electronic legal deposit, the National Library has concentrated on large-scale web harvesting. Depositing of e-books is being tested with publishers. The future plans concerning digital preservation will be presented, especially the National Digital Library initiative.

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