Chemical Similarity and Threshold of Toxicological Concern (TTC) Approaches: Report of an ECB Workshop held in Ispra, November 2005

There are many national, regional and international programmes – either regulatory or voluntary – to assess the hazards or risks of chemical substances to humans and the environment. The first step in making a hazard assessment of a chemical is to ensure that there is adequate information on each of the endpoints. If adequate information is not available then additional data is needed to complete the dataset for this substance. For reasons of resources and animal welfare, it is important to limit the number of tests that have to be conducted, where this is scientifically justifiable. One approach is to consider closely related chemicals as a group, or chemical category, rather than as individual chemicals. In a category approach, data for chemicals and endpoints that have been already tested are used to estimate the hazard for untested chemicals and endpoints. Categories of chemicals are selected on the basis of similarities in biological activity which is associated with a common underlying mechanism of action. A homologous series of chemicals exhibiting a coherent trend in biological activity can be rationalised on the basis of a constant change in structure. This type of grouping is relatively straightforward. The challenge lies in identifying the relevant chemical structural and physicochemical characteristics that enable more sophisticated groupings to be made on the basis of similarity in biological activity and hence purported mechanism of action. Linking two chemicals together and rationalising their similarity with reference to one or more endpoints has been very much carried out on an ad hoc basis. Even with larger groups, the process and approach is ad hoc and based on expert judgement. There still appears to be very little guidance about the tools and approaches for grouping chemicals systematically. In November 2005, the ECB Workshop on Chemical Similarity and Thresholds of Toxicological Concern (TTC) Approaches was convened to identify the available approaches that currently exist to encode similarity and how these can be used to facilitate the grouping of chemicals. This report aims to capture the main themes that were discussed. In particular, it outlines a number of different approaches that can facilitate the formation of chemical groupings in terms of the context under consideration and the likely information that would be required. Grouping methods were divided into one of four classes – knowledge-based, analogue-based, unsupervised, and supervised. A flowchart was constructed to attempt to capture a possible work flow to highlight where and how these approaches might be best applied.JRC.I.3-Toxicology and chemical substance

Post-Franco Theatre

In the multiple realms and layers that comprise the contemporary Spanish theatrical landscape, “crisis” would seem to be the word that most often lingers in the air, as though it were a common mantra, ready to roll off the tongue of so many theatre professionals with such enormous ease, and even enthusiasm, that one is prompted to wonder whether it might indeed be a miracle that the contemporary technological revolution – coupled with perpetual quandaries concerning public and private funding for the arts – had not by now brought an end to the evolution of the oldest of live arts, or, at the very least, an end to drama as we know it

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Benito Pérez Galdós

In Galdós\u27 time, the tensions between such diverse phenomena as coins and credit, free trade and protectionist tariffs, factory work and domestic economy, masculine and feminine, and private and public exacerbated friction among peoples—those of pueblo and rural origins, whose voices rasped and whose bright colors raked the eye, and a nascent, insecure bourgeosie who, fearful of the masses, strove to imitate the aristocracy. Old and new converged also with the question of suffrage and citizenship to aggravate social malaise and political upheavals—Carlist wars, palace intrigues, the Revolution of 1868 and overthrow of Queen Isabel, the brief reign of Amadeo of Savoy, the aborted First Republic and the Bourbon Restoration (1875-1885), which reached Spain from England in the imported person of Alfonso XII. These turbulent events undergird the cultural, historical, and political events of the novels by Benito Pérez Galdós (1843–1920) to be discussed in this chapter. Galdós is the author of seventy-seven novels, twenty-six original plays, and numerous occasional pieces, written between 1867 and 1920. These divide into two main categories: the historical and the contemporary social novels, now more appropriately described as novels of modernity The forty-six historical novels, called Episodios nacionales, make up five series, each consisting of ten interconnected novels, except the fifth series, left unfinished. The thirty-one novels of modernity, published between 1870 and 1915, also divide into two groups: Novelas de la primera época ( Novels of the Early Period, 1870–1879) and Las novelas de la serie contemporánea ( The Contemporary Social Novels, 1881–1915). The novels of the early period comprise Galdós\u27 first attempts at novel writing, as well as four so-called thesis novels : Doña Perfecta (1876), the sequel Gloria (1876–1877), Marianela (1878), and La familia de León Roch ( The Family of León Roch, 1878–1879). The next group of novels represents what Galdós called his segunda manera —his second style, a different kind of writing ... a more sophisticated and varied mode of narrative presentation