| 1. |
- Asp, Vendela, et al.
(författare)
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CYTOTOXICITY AND DECREASED CORTICOSTERONE PRODUCTION IN ADRENOCORTICAL CELLS BY METHYLSULPHONATED DERIVATIVES OF p,p′-DDE
- 2007
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Konferensbidrag (refereegranskat)abstract
- 3-methylsulphonyl-DDE (3-MeSO2-DDE) undergoes bioactivation by cytochrome P450 11B1 (CYP11B1) in the adrenal cortex of several animal species in vivo. The activated compound induces cell death in the adrenocortical zona fasciculata and decreases glucocorticoid production. We have in the present study reproduced both the cytotoxicity and the decreased hormone production in vitro using the mouse adrenocortical cell line Y-1. Cytotoxicity was inhibited by the CYP11-inhibitor etomidate, confirming that CYP11-dependent bioactivation takes place also in vitro. Moreover, 3-MeSO2-DDE decreased corticosterone production in a concentration-dependent manner both in cells that had been induced with forskolin and in non-induced cells. In addition, we have investigated the effects on cell viability and corticosterone production of three structurally related compounds. 2-MeSO2-DDE and 3,3′(bis)-MeSO2-DDE induced cytotoxicity, although to a lower degree than 3-MeSO2-DDE. In contrast, the parent compound p,p′-DDE was not cytotoxic, indicating that the methylsulphonyl moieties are required for biological activity. This study shows that by using the basic structures of 3-MeSO2-DDE in drug design we can easily screen for biologically active compounds in the development of new adrenocorticolytic drugs for adrenocortical cancer and Cushing’s syndrome. We consider the Y-1 and other adrenocortical cell lines to be useful tools in overcoming the gap between animal studies and estimation of potential therapeutic effects and/or risks in humans.
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| 2. |
- Asp, Vendela, et al.
(författare)
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Cytotoxicity and decreased corticosterone production in adrenocortical Y-1 cells by 3-methylsulfonyl-DDE and structurally related molecules
- 2009
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 83:4, s. 389-396
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Tidskriftsartikel (refereegranskat)abstract
- The persistent environmental pollutant 3-methylsulfonyl-DDE (3-MeSO2-DDE) undergoes bioactivation by cytochrome P450 11B1 (CYP11B1) in the adrenal cortex of several animal species in vivo and causes decreased glucocorticoid production and cell death in the zona fasciculata. This study presents extended investigations of the cytotoxic and endocrine disrupting effects of 3-MeSO2-DDE and some structurally related molecules in the mouse adrenocortical cell line Y-1. Both 3-MeSO2-DDE and, to a lesser extent, 3,3'(bis)-MeSO2-DDE decreased corticosterone production and produced CYP11B1-dependent cytotoxicity in Y-1 cells. Neither 2-MeSO2-DDE nor p,p'-DDE had any significant effect on either cell viability or corticosterone production, indicating that the presence and position of the methylsulfonyl moiety of 3-MeSO2-DDE is crucial for its biological activity. The adrenocortical toxicant o,p'-DDD decreased corticosterone production but was not cytotoxic in this cell line. None of the compounds altered Cyp11b1 gene expression, indicating that 3-MeSO2-DDE inhibits CYP11B1 activity on the protein level.
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| 3. |
- Björk, Jonas, et al.
(författare)
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Prediction of relative glomerular filtration rate in adults: New improved equations based on Swedish Caucasians and standardized plasma-creatinine assays.
- 2007
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 67:7, s. 678-695
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate newly developed equations predicting relative glomerular filtration rate(GFR) in adult Swedish Caucasians and to compare with the Modification of Diet in Renal Disease(MDRD) and Mayo Clinic equations using enzymatic and zero-calibrated plasma creatinine assays. MATERIAL AND METHODS: GFR was measured with iohexol clearance adjusted to 1.73 m(2). One population sample (n=436/Lund) was used to derive an equation based on plasma-creatinine/age/gender, and a second with the addition of lean body mass (LBM). Both equations were validated in a separate sample (n=414/Malmö). The coefficients of the equations were eventually fine-tuned using all 850 patients and yielding Lund-Malmö equations without (LM) and with LBM-term (LM(LBM)).Their performance was compared with the MDRD(CC) (conventional creatinine calibration), MDRD(IDMS) (isotope dilution mass spectroscopy traceable calibration) and Mayo Clinic equations. RESULTS: The Lund equations performed similarly in both samples. In the combined set, the Mayo Clinic/MDRD(CC) resulted in +19.0/+10.2 % median bias, while bias for the other equations was < 10 %. LM(LBM) had the highest accuracy (86 % of estimates within 30 % of measured GFR), significantly (p < 0.001) better than for MDRD(IDMS) (80 %). In men with BMI < 20 kg/m(2), MDRD(IDMS)/LM had +46 %/+19 % median bias. MDRD(IDMS) also overestimated GFR by 22 %/14 % in men/women above 80 years of age. The LM(LBM) equation had < 10 % bias irrespective of BMI, age or GFR except for a 15 % negative bias at GFR > 90 mL/min/1.73 m(2). CONCLUSION: The newly developed Lund-Malmö equations for GFR estimation performed better than the MDRD(IDMS) and Mayo Clinic equations in a Swedish Caucasian sample. Inclusion of an LBM term improved performance markedly in certain subgroups.
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| 4. |
- Blirup, Soren, et al.
(författare)
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Standardization of Cystatin C: development of primary and secondary reference preparations.
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68:s241, s. 67-70
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Tidskriftsartikel (refereegranskat)abstract
- A Primary Reference Preparation has been produced using pure, recombinant, Cystatin C in a solvent of 0.1 mol/L KCl. Dry mass determination of the Primary Reference Preparation resulted in a Cystatin C concentration of 5.20 g/L. Agarose-electrophoresis and SDS-electrophoresis, as well as N-terminal sequencing, verified the purity, homogeneity and identity of Cystatin C in the Primary Reference Preparation. For the Secondary Reference Preparation, a serum pool was collected and stabilized. A pilot batch was made to verify the selected procedure and spiking with the pure, recombinant Cystatin C. The final Secondary Reference Preparation is now produced (4468 vials) and ready for value assignment and further characterization.
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| 5. |
- Brage, M, et al.
(författare)
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Different cysteine proteinases involved in bone resorption and osteoclast formation.
- 2005
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 76:6, s. 439-47
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Tidskriftsartikel (refereegranskat)abstract
- Cysteine proteinases, especially cathepsin K, play an important role in osteoclastic degradation of bone matrix proteins and the process can, consequently, be significantly inhibited by cysteine proteinase inhibitors. We have recently reported that cystatin C and other cysteine proteinase inhibitors also reduce osteoclast formation. However, it is not known which cysteine proteinase(s) are involved in osteoclast differentiation. In the present study, we compared the relative potencies of cystatins C and D as inhibitors of bone resorption in cultured mouse calvariae, osteoclastogenesis in mouse bone marrow cultures, and cathepsin K activity. Inhibition of cathepsin K activity was assessed by determining equilibrium constants for inhibitor complexes in fluorogenic substrate assays. The data demonstrate that whereas human cystatins C and D are equipotent as inhibitors of bone resorption, cystatin D is 10-fold less potent as an inhibitor of osteoclastogenesis and 200-fold less potent as an inhibitor of cathepsin K activity. A recombinant human cystatin C variant with Gly substitutions for residues Arg8, Leu9, Val10, and Trp106 did not inhibit bone resorption, had 1,000-fold decreased inhibitory effect on cathepsin K activity compared to wildtype cystatin C, but was equipotent with wildtype cystatin C as an inhibitor of osteoclastogenesis. It is concluded that (i) different cysteine proteinases are likely to be involved in bone resorption and osteoclast formation, (ii) cathepsin K may not be an exclusive target enzyme in any of the two systems, and (iii) the enzyme(s) involved in osteoclastogenesis might not be a typical papain-like cysteine proteinase.
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| 6. |
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| 7. |
- Frohm, Jörgen, 1972, et al.
(författare)
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Levels of automation in manufacturing
- 2008
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Ingår i: Ergonomia - an International journal of ergonomics and human factors. - 0137-4990. ; 30:3, s. 29-
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this paper is to increase the general understanding of task allocation in semi-automated systems and to provide a systematic approach for changing the level of automation. The paper presents a literature review of definitions and taxonomies for levels of automation (LoA) across multiple scientific and industrial domains. A synthesizing concept is suggested, including a LoA definition and taxonomy aimed for application in the manufacturing domain. Results suggest that the level of automation should be divided into two separate variables, i.e. physical/mechanical LoA and cognitive/information-related LoA. Further, the idea is that LoA in a manufacturing context can be described and assessed using seven-step reference scales for both physical and cognitive LoA.
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| 8. |
- Frohm, Jörgen, et al.
(författare)
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The Industry's View on Automation in Manufacturing
- 2006
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Ingår i: Poster at the 9th IFAC Symposium on Automated Systems Based on Human Skill and Knowledge.
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Konferensbidrag (populärvet., debatt m.m.)abstract
- Many manufacturing companies in Europe are presently focusing on automation as a weapon for competition on a global market. This paper focuses on industry’s view of automation. The paper presents data on advantages and disadvantages of automation, based on one pilot study and one Delphi study in two rounds.
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| 9. |
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| 10. |
- Grubb, Anders, et al.
(författare)
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Simple Cystatin C-Based Prediction Equations for Glomerular Filtration Rate Compared with the Modification of Diet in Renal Disease Prediction Equation for Adults and the Schwartz and the Counahan-Barratt Prediction Equations for Children.
- 2005
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 51:8, s. 1420-1431
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Serum creatinine is the most commonly used marker for estimation of glomerular filtration rate (GFR). To compensate for its drawbacks as a GFR marker, several prediction equations including several parameters are being used, with the Modification of Diet in Renal Disease (MDRD), Schwartz, and Counahan-Barratt equations being the ones most widely accepted for estimation of relative GFR in mL x min(-1) x (1.73 m(2))(-1). The present study analyzes whether these GFR prediction equations for adults and children might be replaced by simple prediction equations based on plasma concentrations of cystatin C.METHODS: Data from 536 patients (0.3-93 years), consecutively referred for determination of GFR by an invasive gold standard procedure, were used for the analysis. Calculations of bias (median percentage of error), correlation (adjusted R(2)), and percentage of estimates within 30% and 50% of measured GFR were used in the comparisons.RESULTS: A cystatin C-based prediction equation using only concentration in mg/L and a prepubertal factor: GFR [mL x min(-1) x (1.73 m(2))(-1)] = 84.69 x cystatin C (mg/L)(-1.680) x 1.384 (if a child <14 years) assessed GFR equally well or better than the simplified MDRD, the Schwartz, and the Counahan-Barratt prediction equations for the adult (> or =18 years) and juvenile groups of the investigated cohort. Age did not influence the cystatin C-based prediction equation for adults, whereas gender did, but with a factor close to unity (0.948 for females).CONCLUSION: A GFR prediction equation based solely on cystatin C (in mg/L) and a prepubertal factor might replace the simplified MDRD prediction equation for adults and the Schwartz and Counahan-Barratt prediction equations for children.
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| 11. |
- Kristensen, Karl, et al.
(författare)
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Cystatin C, beta-2-microglobulin and beta-trace protein in pre-eclampsia
- 2007
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 86:8, s. 921-926
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Tidskriftsartikel (refereegranskat)abstract
- Background. An altered renal function is an essential component of the patho-physiology of pre-eclampsia. The plasma levels of low molecular mass proteins, e. g. beta-trace protein, beta-2-microglobulin and cystatin C, are increased in the third trimester of normal pregnancy. The plasma levels of cystatin C and beta-2-microglobulin are further increased in preeclampsia, and the cystatin C level has been reported to be a reliable marker for the disease. The aim of this investigation was to study the plasma levels of beta-trace protein, beta-2-microglobulin and cystatin C in pre-eclampsia, and to determine the diagnostic performance of these proteins compared to that of urate and creatinine. Methods. A case-control study of 57 women diagnosed with pre-eclampsia, and 218 healthy women with uncomplicated singleton pregnancies in the third trimester. Women in the catchment area of Lund, Sweden, were included during an 18-month period from October 2003 to April 2005. Venous blood samples were drawn upon inclusion when diagnosis was made. The maternal plasma concentrations of the 3 proteins were analysed by automated particle-enhanced immunoturbidimetric assays. Results. The plasma levels of the 3 proteins were significantly higher in the third trimester of pre-eclamptic patients compared to healthy pregnant women in the third trimester. The upper reference limits ( parametric 97.5 percentile) were 2.57 mg/l for beta-2-microglobulin, 0.72 mg/l for beta-trace protein and 1.37 mg/l for cystatin C. ROC analysis showed similar diagnostic performance for the 3 proteins, with b-trace protein displaying the best diagnostic performance of all the analytes. Conclusions. In this study, the maternal plasma levels of beta 2-microglobulin, beta-trace protein and cystatin C were all significantly elevated in pre-eclampsia compared to those of healthy pregnant women, and displayed similar diagnostic performance for diagnosing pre-eclampsia. The results indicate that low molecular mass proteins are useful as markers of renal impairment in pre-eclampsia.
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| 12. |
- Kristensen, Karl, et al.
(författare)
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Increased plasma levels of ss(2)-microglobulin, cystatin C and ss-trace protein in term pregnancy are not due to utero-placental production.
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 649-653
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Tidskriftsartikel (refereegranskat)abstract
- Objective . To study concentration gradients of the low molecular mass proteins, ss(2)-microglobulin, cystatin C and ss-trace protein, between the uterine and ante-cubital veins, the umbilical artery and vein and in the amniotic fluid compartment. Material and methods. The study comprised 27 healthy women with uncomplicated pregnancies undergoing caesarean section at term. Samples were collected simultaneously and paired t-tests were used to compare mean plasma concentrations. Results . There was no significant concentration gradient in the plasma levels of ss(2)-microglobulin, cystatin C or ss-trace protein between the uterine and antecubital veins. There were no correlations between the protein levels in the compartments. Conclusion . The utero-placental unit does not contribute significantly to the maternal levels of ss(2)-microglobulin, cystatin C and ss-trace protein in normal pregnancy, and the proteins are not likely to be transferred across the placental barrier.
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| 13. |
- Kristensen, Karl, et al.
(författare)
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Serum Amyloid A Protein and C-Reactive Protein in Normal Pregnancy and Preeclampsia.
- 2009
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Ingår i: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 1423-002X .- 0378-7346. ; 67:4, s. 275-280
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To study plasma levels of serum amyloid A protein and C-reactive protein in pregnant women with and without preeclampsia and non-pregnant women. Plasma levels of haptoglobin, orosomucoid and ceruloplasmin were also analyzed. Methods: The study included 295 women with uncomplicated pregnancies, 57 women diagnosed with preeclampsia, and 58 healthy non-pregnant women. Plasma concentrations of acute phase proteins were analyzed by particle-enhanced immunoassays. Non-parametric Kruskal-Wallis and Mann-Whitney U tests were used to test differences between the groups. Results: Plasma levels of C-reactive protein and ceruloplasmin were increased in pregnant women with and without preeclampsia compared to non-pregnant women. Plasma levels of serum amyloid A protein and C-reactive protein were not elevated in women with preeclampsia compared to women with normal pregnancy. Conclusion: The description of preeclampsia as a systemic inflammatory state was not reflected in the plasma levels of serum amyloid A protein and C-reactive protein.
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| 14. |
- Kristensen, Karl, et al.
(författare)
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Temporal changes of the plasma levels of cystatin C, beta-trace protein, beta(2)-microglobulin, urate and creatinine during pregnancy indicate continuous alterations in the renal filtration process
- 2007
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 67:6, s. 612-618
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To determine the plasma levels of the renal functional markers creatinine, urate, cystatin C, beta(2)-microglobulin and beta-trace protein in samples from the first, second, early third and late third trimesters of 398 healthy women with uncomplicated singleton pregnancies. Material and methods. Plasma samples from 58 healthy non-pregnant women served as controls. The creatinine levels were significantly lower at all time-points in pregnancy, whereas the urate levels were lower during the first and second trimesters but increased in the late third trimester. The cystatin C, beta(2)-microglobulin and beta-trace protein levels displayed similar changes with increased levels in the third trimester but unaltered levels during the first and second trimesters. Results. The results indicate an increased filtration of low-molecular weight molecules during pregnancy, particularly during the first and second trimesters, whereas filtration of 10-30 kDa molecules is decreased in the third but unaltered in the first and second trimesters. The levels of albumin and alpha(2)-macroglobulin were measured in the same samples. Conclusions. The albumin levels decreased in the second and third trimesters, whereas the levels of alpha(2)-macroglobulin were unchanged, which is compatible with a virtually unaltered transfer of alpha(2)-macroglobulin between the intra-and extravascular space during pregnancy and a significantly increased extravascular fraction of albumin.
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| 15. |
- Lindström, Veronica, 1978-
(författare)
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Adrenocorticolysis Induced by 3-MeSO2-DDE : Mechanisms of Action, Kinetics and Species Differences
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The DDT metabolite 3-methylsulphonyl-DDE (3-MeSO2-DDE) induces cell death specifically in the adrenal cortex of mice after a cytochrome P45011B1 (CYP11B1)-catalysed bioactivation. This substance is not only an environmental pollutant, but also a suggested lead compound for an improved chemotherapy of adrenocortical carcinoma (ACC). The aim of the thesis was to further investigate this compound in terms of kinetics, cell death mechanisms and species differences. The pharmacokinetics of 3-MeSO2-DDE and the current drug for ACC, o,p’-DDD, was studied during 6 months following a single dose in minipigs. The elimination was slower for 3-MeSO2-DDE than for o,p’-DDD, indicated by a lower clearance and longer t½ in plasma and subcutaneous fat. Both substances remained in fat tissue during the whole study period. Unlike o,p’-DDD, 3-MeSO2-DDE was retained also in liver. The adequacy of the murine adrenocortical cell line Y-1 was evaluated for studies of adrenotoxic compounds. The Y-1 cells proved to be an appropriate test system for future mechanism studies, since CYP-catalysed irreversible binding, inhibited corticosterone production induced by 3-MeSO2-DDE and o,p’-DDD were successfully demonstrated. Cell death of 3-MeSO2-DDE in the mouse adrenal cortex was implied to be necrotic. Early apoptotic signalling (i.e. up-regulation of caspase-9) was observed, although it seemed to be interrupted by ATP-depletion and anti-apoptotic actions by heat shock protein 70, resulting in lack of activation of caspase-3. Using cultured adrenal tissue slices, two not previously studied species were examined ex vivo regarding adrenal binding of 3-MeSO2-[14C]DDE. Binding was found in the hamster adrenal cortex and in assumed cortical cells in the medulla, while the guinea pig adrenal was devoid of binding. This emphasises the species specificity in bioactivation of 3-MeSO2-DDE. The thesis forms a basis for further investigations in the human adrenocortical cell line H295R and provides new knowledge of importance for toxicological risk assessment of 3-MeSO2-DDE.
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| 16. |
- Lindström, Veronica, et al.
(författare)
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Choosing Levels of Automation in Production Systems : Finding Critical and Supportive Factors
- 2005
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Ingår i: Proceedings of the 12th International EurOMA Conference on Operations and Global Competitiveness, Budapest, Hungary, June 19-22, 2005. ; , s. 1593-1601, s. 1593-1601
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Operation and strategic decision making becomes more complex and dynamic related to the performance of industrial companies. In this light, the choice of a suitable and right automation level becomes critical and is a non-trivial decision making process. The purpose of this paper is to present definitions of manufacturing strategy, operational flexibility and automation levels in manufacturing. Further, this paper discusses linkages between process technology life stages, manufacturing strategy and levels of automation. A framework presenting critical and supportive factors affected by the choice of level of automation both short and long term give the basics for designating responsibilities to different categories of manufacturing managers. The choice of automation levels can be seen from and should be considered within different dimensions: (1) process life cycle stage; (2) fit with manufacturing strategy; and (3) organizational level.
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| 17. |
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| 18. |
- Lindström, Veronica, 1966-, et al.
(författare)
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Developing a methodology based on Value Stream Mapping for the Measurement of Automation Levels in Production Systems
- 2005
-
Ingår i: CIRP 3rd International Conference on Reconfigurable Manufacturing.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- From a production system perspective, both human and technological capabilities, automation, are important for balance and robustness. Separating and standardizing the balance allocation or relationship between theses two is termed levels of automation (LoA). The purpose of this paper is to investigate the use of Value Stream Mapping to measure levels of automation in production value streams and to discuss suitable types of taxonomies for measuring automation. The results of two case studies show that different LoA models can be used when measuring, but preferable is to separate computerized and mechanized processes. A measurement methodology is also provided based on value stream mapping.
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| 19. |
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| 20. |
- Lindström, Veronica, et al.
(författare)
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Different elimination patterns of beta-trace protein, beta(2)-microglobulin and cystatin C in haemodialysis, haemodiafiltration and haemofiltration.
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 685-691
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Low molecular mass proteins (LMMP) are putative uraemic toxins, but their elimination is negligible in standard haemodialysis (HD). In this study, we used beta(2)-microglobulin, cystatin C and beta-trace protein, which differ in molecular mass and charge, to characterize the elimination patterns of three different dialysis modalities. Material and methods. Plasma samples were obtained at the start, 30 min after the start, at the end of the dialysis treatment and 30 min after termination of the dialysis session. Seventeen patients were treated with low-flux HD, 13 with post-dilution haemodiafiltration (HDF) and 8 with pre-dilution haemofiltration (HF). The changes in concentrations of the three LMMPs were monitored and expressed as percentages of the concentrations at the start of treatments. Results. Conventional HD with low-flux membranes showed a high elimination of small molecules (urea and creatinine), but did not reduce the levels of the three LMMPs studied. During HDF and HF, there was a significant decrease in the plasma levels of cystatin C (to 28 % and 44 %, respectively) (p<0.001) and of beta(2)-microglobulin (to 23 % and 33 %, respectively) (p<0.001). However, the level of beta-trace protein was significantly reduced (to 65 %) only after HDF. Conclusions . The three dialysis modalities showed significantly different elimination patterns for the LMMPs studied. Elimination of beta-trace protein was lower than those of cystatin C and beta(2)-microglobulin both in HDF and HF. beta-trace protein was only moderately eliminated by HDF and not at all by HF, and may be a useful marker in the evaluation of different convective therapies.
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| 21. |
- Lindström, Veronica, 1966-, et al.
(författare)
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Embedding levels of automation in manufacturing strategy
- 2008
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Ingår i: Proceedings of the Swedish Production Symposium 2008.
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Konferensbidrag (refereegranskat)abstract
- Research has shown that alignment between manufacturing strategy and decisions regarding automation are often of an ad hoc nature, i.e. the support for automation decisions is poor. Thus, there is clearly a need for developing support tools to find an appropriate level of automation for more efficient and robust production systems. The aim with this paper is to present a methodology for embedding levels of automation as part of the manufacturing strategy formulation process. The methodology for formulating automation strategy presented in this paper contains five steps where the chosen level of automation is aligned with the manufacturing strategy. Together they form an automation strategy, which secures a desired direction of the firm and also supports robustness and reliability of the manufacturing system due to the holistic approach chosen.
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| 22. |
- Lindström, Veronica, 1966-
(författare)
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Formulation of Automation Strategy in Manufacturing Systems : Developing a Methodology for Analysing and choosing Levels of Automation
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the global environment where industrial enterprises strive for competitiveness, the ability to adjust quickly to changing conditions is important. This global industrial context challenges the companies to develop new capabilities. Capacity flexibility is an important measure of competitiveness and one important capability for improving productivity and effectiveness. Available resources contribute to capacity (output) and influence capacity flexibility. Thus, the way resources are managed is important. One way to manage resources within the manufacturing system is to choose resources that are the most suitable for the task performed by adopting task allocation. Task allocation between human and technology therefore becomes central for design of workplaces with optimal performance. This becomes the challenge of automation. However, to make the right decisions on automation and the skills required for the handling of tools and technology is a complex process of decision making for managers. In the light of this, the objective of this thesis is to develop a methodology for analysing and choosing levels of automation with the purpose to formulate automation strategy in manufacturing systems. The analysis is based on measurement of levels of automation and alignment between levels of automation and the business and manufacturing strategies. The application area of the research is the manufacturing industry and in particular assembly lines or cells because of the mixture of human and technological resources. As indicated by the objective, the outcome of this thesis is a structured methodology that analyses possible alternatives of levels of automation weighted against competitive priorities. The methodology consists of five stages: (1) preparation, (2) business and manufacturing strategy, (3) estimation of levels of automation for critical subtasks, (4) analysis of levels of automation, and (5) completion. The methodology supports visibility of results. Depending on where the company has its greatest improvement potential, different starting points in the methodology can be applied. Validation of the methodology indicates that usefulness, use, and satisfaction with the methodology can be seen as good. The issue of considering both humans and technology is critical for the success of the system, as it builds the resources of the manufacturing function. Overcoming barriers in measuring LoA and in aligning resources with market needs is crucial for developing long term automation strategies. Certain criteria of the manufacturing system influence the choice of LoA. Those criteria are production volume and specific product characteristics. Proposed improvements for formulating manufacturing strategy involve a focus on communication and knowledge sharing, introducing measures for learning and knowledge, enhancing interactions between inside and outside partners, and closing knowledge gaps. Those improvements should be seen primarily as research opportunities in the area of manufacturing strategy processes.
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| 23. |
- Lindström, Veronica, et al.
(författare)
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Species differences in 3-methylsulphonyl-DDE bioactivation by adrenocortical tissue
- 2008
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 82:3, s. 159-163
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Tidskriftsartikel (refereegranskat)abstract
- The CYP11B1-activated adrenocortical toxicant 3-methylsulphonyl-DDE (3-MeSO2-DDE) is proposed as a lead compound for an improved chemotherapy for adrenocortical carcinoma. We compared the binding of 3-MeSO2-[C-14]DDE in the adrenal cortex of four rodent species; hamster, guinea pig, mouse and rat, using a precision-cut adrenal slice culture system ex vivo. Localization and quantification of the bound radioactivity were carried out using light microscopy autoradiography and radioluminography. The results revealed major species differences since 3-MeSO2-[C-14]DDE was extensively bound to the hamster adrenal tissue while the guinea pig adrenals were devoid of binding. A high binding in mouse adrenal cortex was confirmed while binding in rat adrenal cortex was very weak. The results support previous observations that metabolic activation of 3-MeSO2-DDE is highly species dependent. Since CYP11B1 could be expressed in tissues other than the adrenal cortex, final toxicological characterization should be carried out in a species that can bioactivate this compound.
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| 24. |
- Nyman, U., et al.
(författare)
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Standardization of p-creatinine assays and use of lean body mass allow improved prediction of calculated glomerular filtration rate in adults: A new equation
- 2006
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 66:6, s. 451-468
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate the Cockcroft - Gault (CG) equation, using various body weight expressions, and the Sawyer equation in predicting glomerular filtration rate (GFR) using an enzymatic and zero-calibrated Jaffe plasma-creatinine assay, and to derive a new robust equation in adults. Material and methods. The CG weight measures included total, ideal and adjusted body weight (ABW; lowest of total and ideal) and two lean body mass (LBM) expressions, while the Sawyer equation is based primarily on LBM. Iohexol clearance was used to measure GFR. One derivation set (n = 436; enzymatic assay) was used to evaluate and bias-adjust existing equations when indicated, and to derive a new equation based on plasma-creatinine, age, gender and the body weight measure yielding the best adjusted R-2. All equations were then validated in a separate set (n = 414; Jaffe assay). Results. The existing equations all performed similarly in both sets. Prediction errors of equations based on LBM showed no correlation with BMI. The CG(ABW) and Sawyer equations performed best. The new equation with LBM yielded the highest adjusted R-2. In the combined set (n = 850), its accuracy (86%/98% of estimates within 30%/50% of measured GFR) was significantly better than for the CGABW (79%/95%) and Sawyer equations (79%/93%) (p < 0.001) for each 30 mL/min GFR subgroup within +/- 30% and +/- 50%, except within +/- 30% > 120 mL/min. Prediction error did not correlate with BMI, age or gender. Conclusion. A new creatinine-based equation derived in a mainly Caucasian patient sample is a better predictor of GFR than CG-type equations irrespective of the body weight measure used or, if bias-adjusted, when using zero-calibrated creatinine assays.
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| 25. |
- Nyman, Ulf, et al.
(författare)
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The Lund-Malmo creatinine-based glomerular filtration rate prediction equation for adults also performs well in children
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68:7, s. 568-576
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Tidskriftsartikel (refereegranskat)abstract
- Objective . To evaluate the clinical performance in a paediatric population of the Lund-Malmo creatinine-based glomerular filtration rate (GFR) prediction equations, primarily developed for adults. Material and methods . Iohexol clearance was used as the gold standard in 85 paediatric Caucasian patients (0.3-17 years; 37 F/48 M). One Lund-Malmo equation was based on age and gender (LM) and one included lean body mass (LM-LBM). Comparisons focused on correlation (adjusted R-2), bias (median percent error) and accuracy (proportions of predicted GFR differing <= 30 % from measured GFR) (mL/min/1.73 m(2)). The performances were compared with those of the Modification of Diet in Renal Disease (MDRD) Study equation, a dedicated paediatric creatinine equation, Counahan-Barratt (CB) and a cystatin C-based equation. Results . The MDRD equation performed poorly with a median bias of 96 %. Of the remaining equations, only the LM-LBM produced significant bias (+10 % in median) according to line of identity regression analysis. The LM equation yielded marginally higher accuracy (76 %) than the LM-LBM equation (74 %) and the CB (73 %), but lower than the cystatin C-based equation (82 %). However, the estimated accuracy figures for these four equations were generally imprecise and none of the differences compared with the LM equation was statistically significant. Conclusion . In contrast to most creatinine-based GFR prediction equations, the LM equation performs adequately for both children and adults. This may be due to the unique model-building principles used when the LM equation was established. Further validation in a larger paediatric population is necessary.
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| 26. |
- Wahlbom, Maria, et al.
(författare)
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Fibrillogenic oligomers of human cystatin C are formed by propagated domain swapping.
- 2007
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 282:25, s. 18318-18326
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Tidskriftsartikel (refereegranskat)abstract
- Cystatin C and the prion protein have been shown to form dimers via three-dimensional domain swapping, and this process has also been hypothesized to be involved in amyloidogenesis. Production of oligomers of other amyloidogenic proteins has been reported to precede fibril formation, suggesting oligomers as intermediates in fibrillogenesis. A variant of cystatin C, with a Leu(68)-> Gln substitution, is highly amyloidogenic, and carriers of this mutation suffer from massive cerebral amyloidosis leading to brain hemorrhage and death in early adulthood. This work describes doughnut-shaped oligomers formed by wild type and L68Q cystatin C upon incubation of the monomeric proteins. Purified oligomers of cystatin C are shown to fibrillize faster and at a lower concentration than the monomeric protein, indicating a role of the oligomers as fibril-assembly intermediates. Moreover, the present work demonstrates that three-dimensional domain swapping is involved in the formation of the oligomers, because variants of monomeric cystatin C, stabilized against three-dimensional domain swapping by engineered disulfide bonds, do not produce oligomers upon incubation under non-reducing conditions. Redox experiments using wild type and stabilized cystatin C strongly suggest that the oligomers, and thus probably the fibrils as well, are formed by propagated domain swapping rather than by assembly of domain-swapped cystatin C dimers.
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| 27. |
- Winroth, Mats, et al.
(författare)
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Automation Strategies : Refinement of Manufacturing Strategy Content
- 2006
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Automated manufacturing systems are regarded as highly productive, which improves company’s competitiveness. Many companies consider automation as either fully automated or entirely manual. This is never true since there is always a combination of automated and manual tasks. The delicate issue is to choose the level of automation, LoA, which is best for the purpose. When planning and implementing automated manufacturing systems, a large number of issues need to be considered. Traditional manufacturing strategy theory however treats automation as one subset of process technology decision category. In our research we have come to the conclusion that automation decisions affect much more of the company’s operation activities. Thus, there is a need for developing the manufacturing strategy field in order to embrace relevant aspects/decisions in all of the decision categories. This paper aims at bridging the gap in traditional manufacturing strategy theory and highlights the additional decisions that are necessary in order to cover automation. The authors suggest a decision support tool that highlights the different actions that are needed when changing the level of automation in manufacturing systems.
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| 28. |
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