| 1. |
- Spahiu, Linda, et al.
(författare)
-
Global Kinetic Mechanism of Microsomal Glutathione Transferase 1 and Insights into Dynamic Enzyme Activation
- 2017
-
Ingår i: Biochemistry. - : AMER CHEMICAL SOC. - 0006-2960 .- 1520-4995. ; 56:24, s. 3089-3098
-
Tidskriftsartikel (refereegranskat)abstract
- Microsomal glutathione transferase 1 (MGST1) has a unique ability to be activated, <= 30-fold, by modification with sulfhydryl reagents. MGST1 exhibits one-third-of-the-sites reactivity toward glutathione and hence heterogeneous binding to different active sites in the homotrimer. Limited turnover stopped-flow kinetic measurements of the activated enzyme allowed us to more accurately determine the KD for the "third" low-affinity GSH binding site (1.4 +/- 0.3 mM). The rate of thiolate formation, k(2) (0.77 +/- 0.06 s(-1)), relevant to turnover, could also be determined. By deriving the steadystate rate equation for a random sequential mechanism for MGST1, we can predict K-M, k(cat), and k(cat)/K-M values from these and previously determined pre-steady-state rate constants (all determined at 5 C). To assess whether the pre-steady-state behavior can account for the steady-state kinetic behavior, we have determined experimental values for kinetic parameters at 5 degrees C. For reactive substrates and the activated enzyme, data for the microscopic steps account for the global mechanism of MGST1. For the unactivated enzyme and more reactive electrophilic substrates, pre steady -state and steady-state data can be reconciled only if a more active subpopulation of MGST1 is assumed. We suggest that unactivated MGST1 can be partially activated in its unmodified form. The existence of an activated subpopulation (approximately 10%) could be demonstrated in limited turnover experiments. We therefore suggest that MSGT1 displays a preexisting dynamic equilibrium between high- and low-activity forms.
|
|
| 2. |
- Sunduru, Naresh, et al.
(författare)
-
N-aryl 2-aryloxyacetamides as a new class of fatty acid amide hydrolase (FAAH) inhibitors
- 2017
-
Ingår i: Journal of enzyme inhibition and medicinal chemistry (Print). - : Informa UK Limited. - 1475-6366 .- 1475-6374. ; 32:1, s. 513-521
-
Tidskriftsartikel (refereegranskat)abstract
- Fatty acid amide hydrolase (FAAH) is a promising target for the development of drugs to treat neurological diseases. In search of new FAAH inhibitors, we identified 2-(4-cyclohexylphenoxy)-N-(3-(oxazolo[4,5-b] pyri-din-2-yl) phenyl) acetamide, 4g, with an IC50 of 2.6 mu M as a chemical starting point for the development of potent FAAH inhibitors. Preliminary hit-to-lead optimisation resulted in 2-(4-phenylphenoxy)-N-(3-(oxazolo[4,5-b] pyridin-2-yl)phenyl) acetamide, 4i, with an IC50 of 0.35 mu M.
|
|
| 3. |
- Alahyari, Hiva, 1979, et al.
(författare)
-
A study of value in agile software development organizations
- 2017
-
Ingår i: Journal of Systems and Software. - : Elsevier BV. - 0164-1212 .- 1873-1228. ; 125, s. 271-288
-
Tidskriftsartikel (refereegranskat)abstract
- The Agile manifesto focuses on the delivery of valuable software. In Lean, the principles emphasise value, where every activity that does not add value is seen as waste. Despite the strong focus on value, and that the primary critical success factor for software intensive product development lies in the value domain, no empirical study has investigated specifically what value is. This paper presents an empirical study that investigates how value is interpreted and prioritised, and how value is assured and measured. Data was collected through semi-structured interviews with 23 participants from 14 agile software development organisations. The contribution of this study is fourfold. First, it examines how value is perceived amongst agile software development organisations. Second, it compares the perceptions and priorities of the perceived values by domains and roles. Third, it includes an examination of what practices are used to achieve value in industry, and what hinders the achievement of value. Fourth, it characterises what measurements are used to assure, and evaluate value-creation activities. (C) 2016 Elsevier Inc. All rights reserved.
|
|
| 4. |
- Berntsson Svensson, Richard, 1978, et al.
(författare)
-
Is role playing in Requirements Engineering Education increasing learning outcome?
- 2017
-
Ingår i: Requirements Engineering. - : Springer Science and Business Media LLC. - 0947-3602 .- 1432-010X. ; 22:4, s. 475-489
-
Tidskriftsartikel (refereegranskat)abstract
- Requirements Engineering has attracted a great deal of attention from researchers and practitioners in recent years. This increasing interest requires academia to provide students with a solid foundation in the subject matter. In Requirements Engineering Education (REE), it is important to cover three fundamental topics: traditional analysis and modeling skills, interviewing skills for requirements elicitation, and writing skills for specifying requirements. REE papers report about using role playing as a pedagogical tool; however, there is a surprising lack of empirical evidence on its utility. In this paper we investigate whether a higher grade in a role playing project have an effect on students' score in an individual written exam in a Requirements Engineering course. Data are collected from 412 students between the years of 2007 and 2014 at Lund University and Chalmers | University of Gothenburg. The results show that students who received a higher grade in the role playing project scored statistically significant higher in the written exam compared to the students with a lower role playing project grade.
|
|
| 5. |
- Berntsson Svensson, Richard, 1978
(författare)
-
Measuring team innovativeness: A multiple case study of agile and lean software developing companies
- 2017
-
Ingår i: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. ; 10611 LNCS, s. 37-51
-
Konferensbidrag (refereegranskat)abstract
- [Context/Background] Innovation is seen as the basis of competitive economy and measuring the innovation process is important fo r organizations. In the literature, focus has been on innovation and innovation capabilities on an organizational level, while few studies has been placed on innovation at team level. Furthermore, organizations tend to focus on the measurement of innovation to input and outputs of the innovation process and ignoring the process in-between. [Goal] This paper explores how a team’s innovation capability is measured, and can be measured in practice in agile and lean software developing companies. [Method] It is based on data collected through semi-structured interviews with 28 practitioners from 11 software developing companies. [Results] The contribution of this study is twofold: First, it characterizes which metrics are used in industry to measure a team’s innovation capability. Second, it identifies which metrics that could be used in practice to measure a team’s innovation capability. [Conclusions] Measuring the performance of the innovation process is not seen as important during product planning and development.
|
|
| 6. |
- Blicharska, Malgorzata, 1979-, et al.
(författare)
-
Shades of grey challenge practical application of the Cultural Ecosystem Services concept
- 2017
-
Ingår i: Ecosystem Services. - : Elsevier BV. - 2212-0416 .- 2212-0416. ; 23, s. 55-70
-
Tidskriftsartikel (refereegranskat)abstract
- Despite rapid advances in development of the ecosystem services (ES) concept, challenges remain for its use in decision making. Cultural ES (CES) have proven particularly difficult to pin down and resultant “shades of grey” impede their consideration by decision-makers. This study undertakes a literature review of CES to highlight the shades of grey, briefly illustrates findings by reference to the Swedish mountain landscape, then addresses potential implications for practical decision making. The concept of CES is complex and difficult to operationalize. The root of confusion appears to be a lack of rigour in identifying CES, hindering identification of proper methods for determining: the ecosystem elements that underpin CES; the beneficiaries of CES and how they value benefits delivered; and how CES may vary in space and time. We conclude by proposing a framework of questions, which we relate to the ES cascade model, that is intended to help researchers and decision-makers to reflect when considering CES. Answers to the questions should enable decision-makers to prioritise policy development or implementation in relation to the differing needs of potentially competing beneficiaries and what needs to be done or not done to the ecosystem, where, when and by whom.
|
|
| 7. |
- Fernandez, Stefania, 1986, et al.
(författare)
-
A Survey of Practitioners Use of Open Innovation
- 2017
-
Ingår i: 43rd Euromicro Conference on Software Engineering and Advanced Applications. - 9781538621417
-
Konferensbidrag (refereegranskat)abstract
- In recent years, the influence of open innovation has become more and more important in the development of software products and services. However, open innovation is still unexplored for software-intensive organizations and its potential impact on the organization's innovative performance. In this paper we present the results of an empirical study carried out to gauge common experiences within open innovation in the requirements engineering process, and to understand the barriers and drivers for using open innovation. A web-based questionnaire was sent out to 54 industry practitioners, of which 35 answered. The results show that open innovation as part of the requirements engineering process is becoming more and more fully exploited from both the outside and inside. Moreover, potential drivers for using open innovation include, new generated ideas and higher costumer benefits, while identified barriers include, hard finding the right partner and lack of innovativeness.
|
|
| 8. |
- Gren, Lucas, et al.
(författare)
-
Is it possible to disregard obsolete requirements? : An initial experiment on a potentially new bias in software effort estimation
- 2017
-
Ingår i: Proceedings - 2017 IEEE/ACM 10th International Workshop on Cooperative and Human Aspects of Software Engineering, CHASE 2017. - : Institute of Electrical and Electronics Engineers Inc.. - 9781538640395 ; , s. 56-61
-
Konferensbidrag (refereegranskat)abstract
- Effort estimation is a complex area in decision-making, and is influenced by a diversity of factors that could increase the estimation error. The effects on effort estimation accuracy of having obsolete requirements in specifications have not yet been studied. This study aims at filling that gap. A total of 150 students were asked to provide effort estimates for different amounts of requirements, and one group was explicitly told to disregard some of the given requirements. The results show that even the extra text instructing participants to exclude requirements in the estimation task, had the subjects give higher estimates. The effect of having obsolete requirements in requirements specifications and backlogs in software effort estimation is not taken into account enough today, and this study provides empirical evidence that it possibly should. We also suggest different psychological explanations to the found effect. © 2017 IEEE.
|
|
| 9. |
- Hellgren, Rikard, 1988-, et al.
(författare)
-
Estimating the effect of ice load on a concrete dams displacement with regression models
- 2017
-
Ingår i: <em>Proceedings ICOLD 2017 International Symposium</em>. - Prag.
-
Konferensbidrag (refereegranskat)abstract
- In colder climates, the ice load is an important factor to consider when assessing the dam safety. The size of the ice load is associated with uncertainties, regarding both its maximum size and seasonal variation. There is today no reliable method to determine the ice load acting on a dam, since available measurements and theories results in a large scatter regarding the maximum ice loads.In this project, the possibility to determine the ice load based on traditional measurements of a dam behavior is investigated. It’s evaluated if the ice thickness is a significant predictor for the displacement of a Swedish arch dam. A case study on inverted pendulums was performed where dynamic regression models were used to calculate the displacement of the dam.The model showed significant results which could explain the displacements. The ice thickness shows an effect on a 5 % significance level. The results indicate that the seasonal ice load is large enough to be traceable, and could be determined from conventional pendulum measurements. Since pendulums are installed on a large number of dams, a method that estimates the ice load from those measurements could vastly reduce uncertainties regarding ice loads on dams.
|
|
| 10. |
- Kuang, Qie, et al.
(författare)
-
Dead-end complex, lipid interactions and catalytic mechanism of microsomal glutathione transferase 1, an electron crystallography and mutagenesis investigation
- 2017
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Microsomal glutathione transferase 1 (MGST1) is a detoxification enzyme belonging to the Membrane Associated Proteins in Eicosanoid and Glutathione Metabolism (MAPEG) superfamily. Here we have used electron crystallography of two-dimensional crystals in order to determine an atomic model of rat MGST1 in a lipid environment. The model comprises 123 of the 155 amino acid residues, two structured phospholipid molecules, two aliphatic chains and one glutathione (GSH) molecule. The functional unit is a homotrimer centered on the crystallographic three-fold axes of the unit cell. The GSH substrate binds in an extended conformation at the interface between two subunits of the trimer supported by new in vitro mutagenesis data. Mutation of Arginine 130 to alanine resulted in complete loss of activity consistent with a role for Arginine 130 in stabilizing the strongly nucleophilic GSH thiolate required for catalysis. Based on the new model and an electron diffraction data set from crystals soaked with trinitrobenzene, that forms a dead-end Meisenheimer complex with GSH, a difference map was calculated. The map reveals side chain movements opening a cavity that defines the second substrate site.
|
|
