Approximating the limit: the interaction between 'almost' and some temporal connectives in Italian

International audienceThis paper focuses on the interpretation of the Italian approximative adverb 'almost' by primarily looking at cases in which it modifies temporal connectives, a domain which, to our knowledge, has been largely unexplored thus far. Consideration of this domain supports the need for a scalar account of the semantics of (close in spirit to Hitzeman's semantic analysis of , in: Canakis et al. (eds) Papers from the 28th regional meeting of the Chicago Linguistic Society, 1992). When paired with suitable analyses of temporal connectives, such an account can provide a simple explanation of the patterns of implication that are observed when modifies locational (e.g. 'when'), directional (e.g. 'until' and 'since'), and event-sequencing temporal connectives (e.g. 'before' and 'after'). A challenging empirical phenomenon that is observed is a contrast between the modification of and by , on the one hand, and the modification of and by the same adverb, on the other. While and behave symmetrically, a puzzling asymmetry is observed between and . To explain the asymmetry, we propose an analysis of and on which the former has the meaning of the temporal comparative 'earlier', while the latter is seen as an atomic predicate denoting temporal succession between events (Del Prete, Nat Lang Semantics 16:157-203, 2008). We show that the same pattern of implication observed for is attested when modifies overt comparatives, and propose a pragmatic analysis of this pattern that uniformly applies to both cases, thus providing new evidence for the claim that is underlyingly a comparative. A major point of this paper is a discussion of the notion of scale which is relevant for the semantics of ; in particular, we show that the notion of Horn (entailment-based) scale is not well-suited for handling modification of temporal connectives, and that a more general notion of scale is required in order to provide a uniform analysis of as a cross-categorial modifier

Detection and elimination of cellular bottlenecks in protein-producing yeasts

Yeasts are efficient cell factories and are commonly used for the production of recombinant proteins for biopharmaceutical and industrial purposes. For such products high levels of correctly folded proteins are needed, which sometimes requires improvement and engineering of the expression system. The article summarizes major breakthroughs that led to the efficient use of yeasts as production platforms and reviews bottlenecks occurring during protein production. Special focus is given to the metabolic impact of protein production. Furthermore, strategies that were shown to enhance secretion of recombinant proteins in different yeast species are presented

Molecular mechanistic associations of human diseases

<p>Abstract</p> <p>Background</p> <p>The study of relationships between human diseases provides new possibilities for biomedical research. Recent achievements on human genetic diseases have stimulated interest to derive methods to identify disease associations in order to gain further insight into the network of human diseases and to predict disease genes.</p> <p>Results</p> <p>Using about 10000 manually collected causal disease/gene associations, we developed a statistical approach to infer meaningful associations between human morbidities. The derived method clustered cardiometabolic and endocrine disorders, immune system-related diseases, solid tissue neoplasms and neurodegenerative pathologies into prominent disease groups. Analysis of biological functions confirmed characteristic features of corresponding disease clusters. Inference of disease associations was further employed as a starting point for prediction of disease genes. Efforts were made to underpin the validity of results by relevant literature evidence. Interestingly, many inferred disease relationships correspond to known clinical associations and comorbidities, and several predicted disease genes were subjects of therapeutic target research.</p> <p>Conclusions</p> <p>Causal molecular mechanisms present a unifying principle to derive methods for disease classification, analysis of clinical disorder associations, and prediction of disease genes. According to the definition of causal disease genes applied in this study, these results are not restricted to genetic disease/gene relationships. This may be particularly useful for the study of long-term or chronic illnesses, where pathological derangement due to environmental or as part of sequel conditions is of importance and may not be fully explained by genetic background.</p

Human, yeast and hybrid 3-phosphoglycerate kinase gene expression in yeast.

When the gene for yeast 3-phosphoglycerate kinase (PGK) is present on a high copy number plasmid in Saccharomyces cerevisiae, 30-40 percent of yeast protein is produced as PGK. However, when the structural part of this gene is replaced by as many as twenty different heterologous genes, production of gene products is greatly reduced--usually by more than 20 fold. This decrease in protein production is accompanied by large decreases in the steady-state levels of mRNA. However, in contrast to these coding sequences, replacement of the yeast PGK structural gene with a human PGK cDNA has little effect on the steady-state mRNA level in yeast. PGK is a two-domain enzyme and its 3-dimensional structure is highly conserved among species. These observations and others have led us to propose that the PGK protein itself might influence its own mRNA levels (Chen et al., Nucleic Acids Res. 12, pp. 8951-8969, 1984). In addition, data is presented here which suggest that the human PGK mRNA is less efficiently translated than the yeast PGK mRNA. Two different mechanisms of controlling gene expression are indicated. Both mechanisms appear to be independent of gene copy number