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- Borgegård, Tomas, et al.
(author)
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Alzheimer's Disease : Presenilin 2-Sparing γ-Secretase Inhibition Is a Tolerable Aβ Peptide-Lowering Strategy
- 2012
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In: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17297-17305
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Journal article (peer-reviewed)abstract
- γ-Secretase inhibition represents a major therapeutic strategy for lowering amyloid β (Aβ) peptide production in Alzheimer's disease (AD). Progress toward clinical use of γ-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The γ-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between Aβ production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1 (PS1) over PS2 subclass of γ-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain Aβ levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious γ-secretase targeting strategy for AD.
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- Danielsson, Marie
(author)
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Development of a new protective group for tryptophan
- 2010
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Licentiate thesis (other academic/artistic)abstract
- A new protective group for the indole nitrogen of the amino acid tryptophan, the Boc-sarcosinoyl-sarcosinolyl (Boc-Sar-Sar) is described. This protective group shows good stability to the reaction conditions used in solid phase peptide synthesis and is incorporated into the peptide as FmocTrp(BocSarSar)OH. When the peptide is cleaved from the resin with trifluoroacetic acid, the Boc group is simultaneously cleaved and N-terminal nitrogen in the Sar-Sar group is exposed. At low pH this amino group is protonated and thereby the peptide will have higher solubility in aqueous solution. High solubility of the peptide is an important factor for the purification of peptides with reversed phase HPLC. During HPLC purification, the protonated Sar-Sar group will remain on the peptide. When the purified peptide is exposed to pH 7,4 the Sar-Sar group will be cleaved and the peptide will be obtained in its fully deprotected form. This new protective group was used for the synthesis of the antimicrobial peptide gramicidin A, an extremely hydrophobic peptide with no ionizable groups and only a few exposed polar functional groups.
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- Dharmowijoyo, Dimas B. E., et al.
(author)
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Day-to-day interpersonal and intrapersonal variability of individuals' activity spaces in a developing country
- 2014
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In: Environment and Planning, B. - : SAGE Publications. - 0265-8135 .- 1472-3417. ; 41:6, s. 1063-1076
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Journal article (peer-reviewed)abstract
- Using the SITRAMP dataset, which was collected in the Jakarta metropolitan area, Indonesia, over four consecutive days, this study examines day-to-day variability of individuals' activity spaces. The impact of individual heterogeneity and variability of transport network conditions on day-to-day variability of activity spaces is also investigated. Results show that individuals' activity spaces vary from day to day and between different individuals. The activity space of other household members was found to be the most significant factor influencing an individual's activity space. Against the common belief in developing countries that better traffic conditions make individuals travel farther, results show that higher road-network travel speed and better road surface conditions within the home zones actually encourage individuals to visit a more compact set of activity locations and/or visit fewer activity locations. Smoother road surface conditions and higher travel speeds within home zones also bring the centroid of activity locations closer to individuals' home locations. Furthermore, day-to-day variability analysis of individual activity spaces showed that weekday activity spaces are more compact than those at weekends. Moreover, it was found that students' activity spaces show most variability, while those of nonworkers have the lowest variability.
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- Dharmowijoyo, Dimas, et al.
(author)
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The Day to Day Variability of Traveller's Activity Travel Pattern in The Jakarta Metropolitan Area
- 2012
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In: TRB 93rd Annual Meeting Compendium of Papers. - : TRB.
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Conference paper (peer-reviewed)abstract
- Using four consecutive days of SITRAMP Data (2004) from the Jakarta Metropolitan Area (JMA), this study examines the interactions between individuals’ activity-travel pattern variables in the context of their daily constraints, resources and external opportunities. The results from our simultaneous equation modeling show that the observed individual’s activity-travel patterns are the result of the complex interactions between each individual’s activity-travel parameters, which vary from day to day. Some of the interactions are similar with the patterns produced by travelers from developed countries, while others are different. Household and individual characteristics are the most significant variables influencing the interactions among individual activity-travel patterns. Different groups of travelers have different trade-off mechanisms. Further analyses on the stability of the activity-travel patterns across different days are provided. Daily commuting time and regular work commitments heavily shape workers’ and students’ flexibility in arranging their travel time and out-of-home time budget, leading them to more stable daily activity-travel patterns than non-workers. The model also shows that highly unpredictable traffic significantly influences workers’ and students’ intra-personal variability in travel time, more so than any other variable.
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- Eriksson, Karin, 1976, et al.
(author)
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Internal interconnections impact on control performance in a thermomechanical pulping process
- 2014
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In: 2009 10th European Control Conference, ECC 2009; Budapest; Hungary; 23 August 2009 through 26 August 2009. - : IEEE. ; , s. 3486-3491
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Conference paper (peer-reviewed)abstract
- Process integration may indeed be advantageous, particularly in a plant-wide economical sense, but there is also a potential risk that unnecessary difficulties are introduced when it comes to process control. This work identified several internal interconnections in a thermomechanical pulp refiner line as a result of an integration approach adopted during the process design. Firstly, a disturbance sensitivity analysis for the overall production process is carried out. Secondly, a simulation model is constructed and using real process data it is found to successfully reflect the complex dynamic behavior observed at the actual plant. The simulation model can provide indications on how the process performance can be improved by process design modifications. The results suggest that the presence of internal interconnections increases the demands on the control system and also set limits for its performance. If control aspects had been considered at the earliest stages of process development, the possibility to achieve satisfactory process performance could have been significantly improved.
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8. |
- Eriksson, K., et al.
(author)
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On techniques for measuring fiber distribution in refining zones
- 2014
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In: International Mechanical Pulping Conference, IMPC 2014; Helsinki; Finland; 2 June 2014 through 5 June 2014.
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Conference paper (peer-reviewed)abstract
- The objective of this research project was to develop measurement techniques to strengthen the knowledge about fiber distribution inside refining zones. A method where light extinction, dynamic pressure and temperature are simultaneously measured at high sampling rates were developed and evaluated on a pilot refiner. The characteristics of the sampled signals were clearly affected by the changes process conditions like changes in production rate, changes in dilution water feed rate and changes in plate gap. It was verified that measurement techniques like this can be used for qualitative studies on fiber distribution inside the refining zones and the results obtained strengthen several earlier hypotheses in the area.
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- Eriksson, Karin, 1976, et al.
(author)
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Pre-study on the establishment of a research collaboration between industrial energy systems and process control at Chalmers
- 2013
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Reports (other academic/artistic)abstract
- The aim of the project described in this report has been to create a platform for collaboration between the research areas of industrial energy systems and process control at Chalmers. The authors of this report, belonging to the division of Heat and Power Technology, the Automatic control group and to CIT Industriell Energi, are convinced that a close collaboration between these areas could generate benefits for the process industry including •Improved efficiency with respect to energy•Improved opportunities to ensure satisfying operability•Improved process stability and product uniformity•Intensified utilization of available process equipment•Increased profitabilityIn accordance with the project scope, an inventory of relevant academic literature and of past and ongoing activities within the relevant research community has been conducted. Firstly, this inventory recognizes that researchers at Lehigh University (US), NTNU (Norway) and Carnegie Mellon University (US) have been strongly involved in the establishment of a research field commonly referred to as Integrated design and control. It is found that the research questions that are in the interest of the project partners largely can be attributed to this field. Other related labels used, and investigated as part of the project, are plant-wide control and heat exchanger network control. In a specific section of the report, definitions of important terms like operability, controllability and flexibility are given and commented on. Secondly, international research groups of special interest that has been identified are presented. In this category, I2C2 at University of Auckland and CAPEC at Technical University of Denmark can be mentioned. Relevant publications of the above mentioned research groups and their associates have been studied and are commented on in the report. Special emphasize has been put on review papers and on recent publications. Furthermore, the project has mapped the competences, experience and interest of the project partners. On this basis, the following keywords were identified:•Retrofit•Bio-based processes•Pulp and paper industry•Real life case studies•Industrial co-operation•Economic evaluation•Simulation•Scale up challengesThis list was used during discussions on research questions and project ideas for future collaboration. This project has provided the partners an opportunity to obtain deeper insight into each other’s knowledge and experiences, and, moreover, research areas of common interest have been recognized. To further develop the collaboration, the next step seems to imply joint participation in specific research projects. Research questions of interest and ideas for future projects are presented in the full report. This relates to the prevailing possibilities to apply for research grant - an issue that is addressed lastly in this report. In relation to this it should be noted that there is a program on Industrial Process Automation, supported by Vinnova, the Swedish Energy Agency and Formas, that is soon to be launched. A strategy for monitoring calls from this program as well as other relevant programs was formulated. As a result of the work in this project, it has also been possible to formulate proposals for two specific PhD-student projects within the Preem-Chalmers cooperation. These proposals take the outcome of this project into account and include opportunities to further develop the collaboration between industrial energy systems and process control at Chalmers.
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10. |
- Fadaei, Masoud, et al.
(author)
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Consistently estimating link speed using sparse GPS data with measured errors
- 2014
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In: Transportation. - : Elsevier. ; , s. 829-838
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Conference paper (peer-reviewed)abstract
- Data sources using new technology such as the Geographical Positioning System are increasingly available. In many different applications, it is important to predict the average speed on all the links in a network. The purpose of this study is to estimate the link speed in a network using sparse GPS data set. Average speed is consistently estimated using Indirect Inference approach. in the end, the Monte Carlo evidence is provided to show that the results are consistent with parameter estimates.
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