| 1. |
- Amiri, Shahnaz, et al.
(författare)
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Simulation and introduction of a CHP plant in a Swedish biogas system
- 2013
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Ingår i: Renewable energy. - Oxford : Elsevier. - 0960-1481 .- 1879-0682. ; 49:SI, s. 242-249
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Tidskriftsartikel (refereegranskat)abstract
- The objectives of this study are to present a model for biogas production systems to help achieve a more cost-effective system, and to analyse the conditions for connecting combined heat and power (CHP) plants to the biogas system. The European electricity market is assumed to be fully deregulated. The relation between connection of CHP. increased electricity and heat production, electricity prices, and electricity certificate trading is investigated. A cost-minimising linear programming model (MODEST) is used. MODEST has been applied to many energy systems, but this is the first time the model has been used for biogas production. The new model, which is the main result of this work, can be used for operational optimisation and evaluating economic consequences of future changes in the biogas system. The results from the case study and sensitivity analysis show that the model is reliable and can be used for strategic planning. The results show that implementation of a biogas-based CHP plant result in an electricity power production of approximately 39 GW h annually. Reduced system costs provide a profitability of 46 MSEK/year if electricity and heat prices increase by 100% and electricity certificate prices increase by 50%. CO2 emission reductions up to 32,000 ton/year can be achieved if generated electricity displaces coal-fired condensing power.
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| 2. |
- Cashin, Peter H, 1984-, et al.
(författare)
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Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer
- 2013
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13, s. 435-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis(PC) is poorly defined. We investigated drug sensitivity ex vivo in patient samples of various PC tumor types and correlated clinical outcome to drug sensitivity within the subset of PC fromcolorectal cancer (CRC). Methods: PC tissue samples (n = 174) from mesothelioma, pseudomyxoma peritonei (PMP), ovarian cancer, CRC or appendix cancer were analyzed ex vivo for sensitivity to oxaliplatin, cisplatin, mitomycin C, melphalan, irinotecan, docetaxel, doxorubicin and 5-FU. Clinicopathological variables and outcome data were collected for the CRC subset. Results: Mesothelioma and ovarian cancer were generally more drug sensitive than CRC, appendix cancer and PMP. Oxaliplatin showed the most favorable ratio between achievable IPC concentration and ex vivo drug sensitivity. Drug sensitivity in CRC varied considerably between individual samples. Ex vivo drug sensitivity did not obviously correlate to time-to-progression (TTP) in individual patients. Conclusions: Drug-sensitivity varies considerably between PC diagnoses and individual patients arguing for individualized therapy in IPC rather than standard diagnosis-specific therapy. However, in the current paradigm of treatment according to diagnosis, oxaliplatin is seemingly the preferred drug for IPC from a drug sensitivity and concentration perspective. Inthe CRC subset, analysis of correlation between ex vivo drug sensitivity and TTP was inconclusive due to the heterogeneous nature of the data.
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| 3. |
- Fridlund, M., et al.
(författare)
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The Search for Worlds Like Our Own
- 2010
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Ingår i: Astrobiology. - : Mary Ann Liebert Inc. - 1531-1074 .- 1557-8070. ; 10:1, s. 5-17
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Tidskriftsartikel (refereegranskat)abstract
- The direct detection of Earth-like exoplanets orbiting nearby stars and the characterization of such planets particularly, their evolution, their atmospheres, and their ability to host life-constitute a significant problem. The quest for other worlds as abodes of life has been one of mankind's great questions for several millennia. For instance, as stated by Epicurus similar to 300 BC: "Other worlds, with plants and other living things, some of them similar and some of them different from ours, must exist.'' Demokritos from Abdera (460-370 BC), the man who invented the concept of indivisible small parts-atoms-also held the belief that other worlds exist around the stars and that some of these worlds may be inhabited by life-forms. The idea of the plurality of worlds and of life on them has since been held by scientists like Johannes Kepler and William Herschel, among many others. Here, one must also mention Giordano Bruno. Born in 1548, Bruno studied in France and came into contact with the teachings of Nicolas Copernicus. He wrote the book De l'Infinito, Universo e Mondi in 1584, in which he claimed that the Universe was infinite, that it contained an infinite amount of worlds like Earth, and that these worlds were inhabited by intelligent beings. At the time, this was extremely controversial, and eventually Bruno was arrested by the church and burned at the stake in Rome in 1600, as a heretic, for promoting this and other equally confrontational issues (though it is unclear exactly which idea was the one that ultimately brought him to his end). In all the aforementioned cases, the opinions and results were arrived at through reasoning-not by experiment. We have only recently acquired the technological capability to observe planets orbiting stars other than our Sun; acquisition of this capability has been a remarkable feat of our time. We show in this introduction to the Habitability Primer that mankind is at the dawning of an age when, by way of the scientific method and 21(st)-century technology, we will be able to answer this fascinating controversial issue that has persisted for at least 2500 years.
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| 4. |
- Henschel, Henning, et al.
(författare)
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Insights into the Isomerisation Mechanism of Warfarin
- 2010
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Konferensbidrag (refereegranskat)abstract
- Warfarin is one of the most commonly used drugs in anticoagulent therapy. Notwithstanding its wide use, achieving correct dosage is often a major challenge due to its narrow therapeutic window.[1] The bioavailability of warfarin is believed to be greatly influenced by the environment-dependent composition of the ensemble of isomers present. While the different structures of warfarin have been discussed in earlier publications,[2] details of the mechanism underlying the formation of the cyclic hemiacetal (Figure 1) had not yet been investigated. Figure 1. Cyclization reaction of warfarin.Figure 2. Transition state in presence of one water molecule. We have now studied the reaction by means of density functional calculations. Comparison of results from calculations performed on the isolated warfarin molecule and in presence of water molecules (compare Figure 2) highlight the importance of intermolecular interactions in the key proton transfer step for the reaction to proceed. A viable model for the mechanism underlying the isomerisation shall be presented. References[1] J. Ansell, J. Hirsh, L. Poller, H. Bussey, A. Jacobsen and E. Hylek, Chest, 126, 204S (2004).[2] B. C. G. Karlsson, A. M. Rosengren, P. O. Andersson and I. A. Nicholls, J. Phys. Chem. B, 111,10520 (2007).
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| 5. |
- Henschel, Henning, et al.
(författare)
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The Mechanistic Basis for Warfarin’s Structural Diversity and Implications for Its Bioavailability
- 2010
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Ingår i: Journal of Molecular Structure. - : Elsevier BV. - 0166-1280. ; 958, s. 7-9
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Tidskriftsartikel (refereegranskat)abstract
- The anticoagulent drug warfarin exhibits chameleon-like isomerism, where the environment-dependent composition of the ensemble of structures greatly influences its bioavailability. Here, the mechanism of conversion between the major isomeric forms is studied. The dramatic differences in transition state energies, as determined by density functional calculations, highlight the necessity for the involvement of intermolecular interactions in the key proton transfer step. A viable model for the mechanism underlying the isomerization reactions is presented.
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| 6. |
- Karlsson, Björn C. G., et al.
(författare)
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How warfarin’s structural diversity influences its phospholipid bilayer membrane permeation
- 2013
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 117:8, s. 2384-2395
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Tidskriftsartikel (refereegranskat)abstract
- The role of the structural diversity of the widely used anticoagulant drug warfarin on its distribution in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayer membranes was investigated using a series of both restrained (umbrella sampling) and unrestrained molecular dynamics simulations. Data collected from unrestrained simulations revealed favorable positions for neutral isomers of warfarin, the open side chain form (OCO), and the cyclic hemiketal (CCO), along the bilayer normal close to the polar headgroup region and even in the relatively distant nonpolar lipid tails. The deprotonated open side chain form (DCO) was found to have lower affinity for the DOPC bilayer membrane relative to the neutral forms, with only a small fraction interacting with the membrane, typically within the polar headgroup region. The conformation of OCO inside the lipid bilayer was found to be stabilized by intramolecular hydrogen bonding thereby mimicking the structure of CCO. Differences in free energies, for positions of OCO and CCO inside the bilayer membrane, as compared to positions in the aqueous phase, were −97 and −146 kJ·mol–1. Kinetic analysis based on the computed free energy barriers reveal that warfarin will diffuse through the membranes within hours, in agreement with experimental results on warfarin’s accumulation in the plasma, thus suggesting a passive diffusion mechanism. We propose that this membrane transport may be an isomerization-driven process where warfarin adapts to the various local molecular environments encountered under its journey through the membrane. Collectively, these results improve our understanding of the influence of warfarin’s structural diversity on the drug’s distribution and bioavailability, which in turn may provide insights for developing new formulations of this important pharmaceutical to better address its narrow therapeutic window.
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| 7. |
- Karlsson, Henning, et al.
(författare)
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Loss of cancer drug activity in colon cancer HCT-116 cells during spheroid formation in a new 3-D spheroid cell culture system
- 2012
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 318:13, s. 1577-1585
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Tidskriftsartikel (refereegranskat)abstract
- Clinically relevant in vitro methods are needed to identify new cancer drugs for solid tumors. We report on a new 3-D spheroid cell culture system aimed to mimic the properties of solid tumors in vivo. The colon cancer cell lines HCT-116 wt and HCT-116 wt/GFP were grown as monolayers and for 3 or 6 days on 96-well NanoCulture (R) plates to form spheroids. Expression of surface markers, genes and hypoxia were assessed to characterize the spheroids and drug induced cytotoxicity was evaluated based on fluorescein diacetate (FDA) conversion by viable cells to fluorescent fluorescein or by direct measurement of fluorescence of GFP marked cells after a 72 h drug incubation. The cells reproducibly formed spheroids in the NanoCulture (R) plates with tight cell-attachment after 6 days. Cells in spheroids showed geno- and phenotypical properties reminiscent of hypoxic stem cells. Monolayer cultured cells were sensitive to standard and investigational drugs, whereas the spheroids gradually turned resistant. Similar results for cytotoxicity were observed using simplified direct measurement of fluorescence of GFP marked cells compared with FDA incubation. In conclusion, this new 3-D spheroid cell culture system provides a convenient and clinically relevant model for the identification and characterization of cancer drugs for solid tumors.
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| 8. |
- Kristensen, Lars Erik, et al.
(författare)
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Is Swollen to Tender Joint Count Ratio a New and Useful Clinical Marker for Biologic Drug Response in Rheumatoid Arthritis? Results From a Swedish Cohort
- 2014
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 66:2, s. 173-179
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo study the impact of swollen to tender joint count ratio (STR) and other baseline characteristics on treatment response to a first course of anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients. MethodsPatients with RA initiating their first course of anti-TNF treatment were included in a structured clinical followup protocol. Based on pragmatic thresholds and plausibility, patients were categorized as having low (STR <0.5), moderate (0.5 STR 1.0), or high (STR >1.0) joint count ratios. The data were collected and followed during the period of March 1999 through December 2010. ResultsA total of 2,507 patients were included in the study (median age 56 years, 78% women). Of these patients, 344 (14%) had a low STR, 1,180 (47%) had a moderate STR, and 983 (39%) had a high STR. According to these STR thresholds, 23% of patients (95% confidence interval [95% CI] 18-29%) with low, 39% (95% CI 35-43%) with moderate, and 40% (95% CI 36-44%) with high STR achieved the American College of Rheumatology criteria for 50% improvement (ACR50) response at 6 months after initiation. Correlation tests showed that STR was associated with ACR50 response independent of both swollen and tender joint counts. Logistic regression analysis consistently showed that moderate STR, high STR, not using prednisolone, high baseline Disease Activity Score in 28 joints, and low baseline Health Assessment Questionnaire scores were significantly associated with favorable ACR50 response with odds ratios of 1.93 (P < 0.01), 2.82 (P < 0.01), 0.65 (P < 0.01), 1.49 (P < 0.01), and 0.47 (P < 0.01), respectively. ConclusionSTR is a new and feasible predictor of treatment response in RA. RA patients with a moderate to high STR have a 2- to 3-fold increased likelihood of responding according to ACR50 criteria.
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| 9. |
- Najjar, Jad, et al.
(författare)
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Towards outcome based learning : an engineering education case
- 2011
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Ingår i: 2011 IEEE Global Engineering Education Conference (EDUCON). - 9781612846415 ; , s. 1039-1048
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Konferensbidrag (refereegranskat)abstract
- Following the European initiatives like European Qualification Framework (EQF), Europass [4] and European Learner Mobility [3], the aim of this paper is to introduce specifications, services and applications that enable the management and use of learning outcome information. We present pilot implementation and validation of the adoption of standards and specifications related to outcome based learning. Prototypes are developed as widgets and modules of Learning Management Systems (LMS) like Moodle, to produce and import data about intended learning outcomes of learning opportunities and achieved learning outcomes of learners. We demonstrate an outcome based Engineering Education use case.
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| 10. |
- Nicholls, Ian A., et al.
(författare)
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Rational design of biomimetic molecularly imprinted materials : theoretical and computational strategies for guiding nanoscale structured polymer development
- 2011
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 400:6, s. 1771-1786
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Forskningsöversikt (refereegranskat)abstract
- In principle, molecularly imprinted polymer science and technology provides a means for ready access to nano-structured polymeric materials of predetermined selectivity. The versatility of the technique has brought it to the attention of many working with the development of nanomaterials with biological or biomimetic properties for use as therapeutics or in medical devices. Nonetheless, the further evolution of the field necessitates the development of robust predictive tools capable of handling the complexity of molecular imprinting systems. The rapid growth in computer power and software over the past decade has opened new possibilities for simulating aspects of the complex molecular imprinting process. We present here a survey of the current status of the use of in silico-based approaches to aspects of molecular imprinting. Finally, we highlight areas where ongoing and future efforts should yield information critical to our understanding of the underlying mechanisms sufficient to permit the rational design of molecularly imprinted polymers.
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