1,186 research outputs found

    Dipeptides in cell culture - Tools for performance increase and risk reduction

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    Supplying mammalian cells with certain amino acids can be challenging. These challenges range from chemically instable components like L-glutamine to barely soluble ones like L-tyrosine. Scientists in the parenteral nutrition space realized early that coupling the troublesome amino acid to another, forming a dipeptide, can be an elegant solution1,2. In the field of cell culture, only glutamine-containing dipeptides have been established. L-alanyl-L-glutamine is the most common peptide, often sold under a variety of trade names, but there are more products with exciting properties that are not commonly used in the field. The study at hand summarizes screenings with two different CHO cell lines that measured the impact of replacing single amino acids with dipeptides. The dipeptides tackle two types of challenges: glutamine stability and solubility enhancement. For the first challenge, alternative glutamine peptides were investigated and compared to the current benchmark. It was found that while all of them offered chemical stability, the impact on cell growth, titer and metabolites were different. This was shown in both batch and fed-batch experiments. For the second challenge, L-tyrosine as well as other critical amino acids were coupled to solubility-increasing amino acids and tested for their capability to replace the free amino acids in a cell culture medium. Especially for a glycyl-L-tyrosine dipeptide, it could be shown that the peptide is utilized by the cells and overcomes the solubility challenge at neutral pH. This is of significant relevance to an industrial cell culture user, as the current solution to formulate a highly concentrated feed containing L-tyrosine is to use a high pH. That introduces a process risk, as a malfunction in process control can lead to a lost batch. Using a L-tyrosine containing dipeptide is shown to be an elegant solution to the challenge. 1 Grimble, GK, Annu. Rev. Nutr. 1994; 14:419-47 2 Fuerst, P, J Nutr. 2001 Sep;131(9 Suppl):2562S-8

    The climate beta

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    How does climate-change mitigation affect the aggregate consumption risk borne by future generations? In other words, what is the ‘climate beta’? In this paper we argue using a combination of theory and integrated assessment modelling that the climate beta is positive and close to unity for maturities of up to about one hundred years. This is because the positive effect on the climate beta of uncertainty about exogenous, emissions-neutral technological progress overwhelms the negative effect on the climate beta of uncertainty about the carbon-climate-response, particularly the climate sensitivity, and the damage intensity of warming. Mitigating climate change therefore has no insurance value to hedge the aggregate consumption risk borne by future generations. On the contrary, it increases that risk, which justifies a relatively high discount rate on the expected benefits of emissions reductions. However, the stream of undiscounted expected benefits is also increasing in the climate beta, and this dominates the discounting effect so that overall the net present value of carbon emissions abatement is increasing in the climate beta

    The climate beta

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    Mitigation reduces the expected future damages from climate change,flbut how does it affect the aggregate risk borne by future generations?flThis raises the question of the ‘climate beta’, i.e., the elasticity of climatefldamages with respect to a change in aggregate consumption. Inflthis paper we show that the climate beta is positive if the main sourceflof uncertainty is exogenous, emissions-neutral technological progress,flimplying that mitigation has no hedging value. But these results areflreversed if the main source of uncertainty is related to the carbonclimate-flresponse and the damage intensity of warming. We then showflthat in the DICE integrated assessment model the climate beta is positivefland close to unity. In estimating the social cost of carbon, thisflwould justify using a relatively high rate to discount expected climatefldamages. However, the stream of undiscounted expected climate damagesflis also increasing in the climate beta. We show that this dominatesflthe discounting effect, so that the social cost of carbon is in fact largerflthan when discounting expected damages at the risk-free rate

    Visual threads: the benefits of multithreading in visual programming languages

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    technical reportAfter working with the CWave visual programming language, we discovered that many of our target domains required the ability to define parallel computations within a program. CWave has a strongly hierarchical model of computation, so it seemed like adding the ability to take a part of the hierarchy and execute it in parallel would provide a good way of solving the problem. This led us to the concept of the Visual Thread and its associated components. Effectively, the Visual Thread allows the programmer to specify a part of the hierarchy and execute that part in parallel with the rest of program. We have used this implementation in several domains and demonstrated that it allows easy mapping of real world problems into our language. It eliminates most of the complexities often associated with programming parallel applications. We have also used a first prototype of our code generation system to translate CWave into Promela which allows us to verify correctness properties of the programs

    The climate beta

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    Mitigation reduces the expected future damages from climate change,flbut how does it affect the aggregate risk borne by future generations?flThis raises the question of the ‘climate beta’, i.e., the elasticity of climatefldamages with respect to a change in aggregate consumption. Inflthis paper we show that the climate beta is positive if the main sourceflof uncertainty is exogenous, emissions-neutral technological progress,flimplying that mitigation has no hedging value. But these results areflreversed if the main source of uncertainty is related to the carbonclimate-flresponse and the damage intensity of warming. We then showflthat in the DICE integrated assessment model the climate beta is positivefland close to unity. In estimating the social cost of carbon, thisflwould justify using a relatively high rate to discount expected climatefldamages. However, the stream of undiscounted expected climate damagesflis also increasing in the climate beta. We show that this dominatesflthe discounting effect, so that the social cost of carbon is in fact largerflthan when discounting expected damages at the risk-free rate

    Diversity and community composition of euglossine bee assemblages (Hymenoptera: Apidae) in western Amazonia

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    Tropical forests are known for their diverse insect fauna. We aimed to determine the effect and relative importance of latitude, elevation and climatic factors affecting species richness and turnover in euglossine bee assemblages along a gradient of 18°latitude from tropical rainforests to subtropical, deciduous dry forests in Peru and Bolivia. Sixteen forest sites were sampled during the dry season. Variance partitioning techniques were applied to assess the relative effects of the spatial and environmental variables on species richness and composition. Furthermore, we conducted a Species Indicator Analysis to find characteristic species for the biogeographic zones. There was a significant decrease in species richness towards the subtropical area. The best predictors of species richness were precipitation and its consequences on soil properties as well as temperature seasonality. The abundance of euglossines was most closely related to precipitation and soil-pH, but the causal links of abundance to these factors is unclear since soil-pH itself is correlated to a drastic turnover of vegetation structure. Based on the analysis of assemblage composition we propose three different assemblages with a transitional zone at the southern tropical area. The biogeographical distribution of euglossine bees along our study transect appears to be primarily related to climatic conditions and does not reflect the common subdividion of Amazonia into drainage system
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