1. |
- Gabrielsson, Britt, 1957, et al.
(författare)
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Molecular characterization of a local sulfonylurea system in human adipose tissue.
- 2004
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Ingår i: Molecular and cellular biochemistry. - 0300-8177 .- 1573-4919. ; 258:1-2, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- ATP-sensitive potassium (KATP) channels are present in many cell types and link cellular metabolism to the membrane potential. These channels are heterooctamers composed of two subunits. The sulfonylurea receptor (SUR) subunits are targets for drugs that are inhibitors or openers of the KATP channels, while the inwardly rectifying K+ (Kir) subunits form the ion channel. Two different SUR genes (SUR1 and SUR2) and two different Kir6.x genes (Kir6.1 and Kir6.2) have been identified. In addition, isoforms of SUR2, SUR2A and SUR2B, have been described. We have previously performed expression profiling on pooled human adipose tissue and found high expression of SUR2. Others have reported expression of SUR1 in human adipocytes. The aim of this study was to characterize the expression of the sulfonylurea receptor complex components in human adipose tissue. RT-PCR analysis, verified by restriction enzyme digestions and DNA sequencing, showed that SUR2B, Kir6.1 and alpha-endosulfine, but not SUR1, SUR2A or Kir6.2, are expressed in human adipose tissue. Real-time RT-PCR showed that SUR2B was expressed at higher levels in subcutaneous compared with omental adipose tissue in paired biopsies obtained from seven obese men (p < 0.05). Analysis of tissue distribution showed that SUR2B expression in adipose tissue was lower than that in muscle, similar to that in heart and liver, while the expression in pancreas was lower. The effect of caloric restriction was tested in obese men (n = 10) treated with very low calorie diet for 16 weeks, followed by a gradual reintroduction of ordinary food for 2 weeks. Biopsies were taken at week 0, 8 and 18. There was no consistent effect of weight reduction on SUR2B or Kir6.1 expression. We conclude that the necessary components for a local sulfonylurea system are expressed in human adipose tissue and that the sulfonylurea receptor complex in this tissue is composed of SUR2B and Kir6.1. The expression of SUR2B was higher in subcutaneous compared with omental adipose tissue and was not affected by weight loss.
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2. |
- Ullmark, Peter, et al.
(författare)
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Design & visuell kommunikation : examensbok 2010
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Publiceras i samband med den första utexamineringen från kandidatprogrammet Design & Visuell Kommunikation på Malmö högskola. Boken innehåller artiklar om designforskning såväl som personliga presentationer av programmets studenter och deras examensarbeten eller portfolios. Boken definierar vad Design & Visuell Kommunikation står för i studenternas mening.
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4. |
- Andersson, Niklas, et al.
(författare)
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Parameter Selection in the Parameter Estimation of Grade Transitions in a Polyethylene Plant
- 2015
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Ingår i: Studies in Engineering and Technology. - : Redfame Publishing. - 2330-2038 .- 2330-2046. ; 3:1, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- A polyethylene plant at Borealis AB is modelled in the Modelica language and considered for parameter estimations at grade transitions. Parameters have been estimated for both the steady-state and the dynamic case using the JModelica.org platform, which offers tools for steady-state parameter estimation and supports simulation with parameter sensitivies. The model contains 31 candidate parameters, giving a huge amount of possible parameter combinations. The best parameter sets have been chosen using a parameter-selection algorithm that identified parameter sets with poor numerical properties. The parameter-selection algorithm reduces the number of parameter sets that is necessary to explore. The steady-state differs from the dynamic case with respect to parameter selection. Validations of the parameter estimations in the dynamic case show a significant reduction in an objective value used to evaluate the quality of the solution from that of the nominal reference, where the nominal parameter values are used.
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- Antonsson, Ann-Beth, et al.
(författare)
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Möjligheter och begränsningar avseende användning av slutningsåtgärder för metallhaltiga vatten
- 1992
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Målsättningen för det här fleråriga projektet är att ta fram ett objektivt tekniskt/ekonomiskt underlag avseende olika separationsteknikers möjligheter och begränsningar att sluta en ytbehandlingsanläggning. Tyngdpunkten ligger på metallbeläggningssidan. I den första delen av projektet har vi på laboratoriet behandlat följande provvattentyper från ytbehandlare. - Sköljvatten från förkromning, förkoppring, förnickling och förzinkning - Totalavlopp efter konventionell fällning. Vi har behandlat vattnen med ett stort antal olika separationstekniker. Jonbyte, omvänd osmos, nanofiltrering, indunstning, elektrolys, elektrodialys, sulfidfällning, aktivt kol. Vad gäller avskiljningen av metall kan man konstatera att det går att producera ett vatten med mycket låga resthalter, framförallt med jonbyte, omvänd osmos och indunstning. Investeringskostnaden för dessa metoder ökar nu i nämnd ordning. Det finns många företag som använder separationstekniker i sina system (framför allt jonbyte). Emellertid används dessa oftast för att återanvända sköljvattnet. De metaller som uppkoncentreras fälls oftast ut som metallhydroxider. För att kunna återföra metaller och andra prestationskemikalier till processbadet krävs det att man uppnår rätt koncentration samtidigt som man inte ska återföra föroreningar till badet. Helst ska dessa blödas ut ur systemet. För de tekniker som studerats var avskiljningsförmågan för metall hög för alla metoder utom aktivt kol. För organiskt material var den hög för omvänd osmos och indunstning. För att kunna bedöma möjligheten att återföra koncentrat till baden krävs det kunskap om korrekt badsammansättning, tolerabla avvikelser samt innehåll i de koncentrat som ska återföras. I den här inledande delen av projektet kan vi konstatera att kunskapen kring dessa frågor många gånger är bristfällig. En genomgång av vilka kemikalier som kan finnas i sköljvattnen och vilka inneboende hälsorisker dessa besitter har sammanställts. Med utgångspunkt från detta har sedan tänkbara hälsorisker som kan uppstå vid slutning diskuterats. I etapp 2 kommer arbetsmiljöaspekterna att belysas ytterligare i samband med pilotkörningarna i fält. Jonbyte, omvänd osmos (RO) och indunstning kommer att utprovas under långvariga och realistiska omständigheter. Dessutom kommer Elektrodialys (ED) och elektrolys att utprovas på mer koncentrerade sparsköljar och koncentrat från de andra metoderna.
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6. |
- Arvidsson McShane, Staffan, 1990-
(författare)
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Confidence Predictions in Pharmaceutical Sciences
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main focus of this thesis has been on Quantitative Structure Activity Relationship (QSAR) modeling using methods producing valid measures of uncertainty. The goal of QSAR is to prospectively predict the outcome from assays, such as ADMET (Absorption, Distribution, Metabolism, Excretion), toxicity and on- and off-target interactions, for novel compounds. QSAR modeling offers an appealing alternative to laboratory work, which is both costly and time-consuming, and can be applied earlier in the development process as candidate drugs can be tested in silico without requiring to synthesize them first. A common theme across the presented papers is the application of conformal and probabilistic prediction models, which are used in order to associate predictions with a level of their reliability – a desirable property that is essential in the stage of decision making. In Paper I we studied approaches on how to utilize biological assay data from legacy systems, in order to improve predictive models. This is otherwise problematic since mixing data from separate systems will cause issues for most machine learning algorithms. We demonstrated that old data could be used to augment the proper training set of a conformal predictor to yield more efficient predictions while preserving model calibration. In Paper II we studied a new approach of predicting metabolic transformations of small molecules based on transformations encoded in SMIRKS format. In this work use used the probabilistic Cross-Venn-ABERS predictor which overall worked well, but had difficulty in modeling the minority class of imbalanced datasets. In Paper III we studied metabolomics data from patients diagnosed with Multiple Sclerosis and found a set of 15 discriminatory metabolites that could be used to classify patients from a validation cohort into one of two sub types of the disease with high accuracy. We further demonstrated that conformal prediction could be useful for tracking the progression of the disease for individual patients, which we exemplified using data from a clinical trial. In Paper IV we introduced CPSign – a software for cheminformatics modeling using conformal and probabilistic methods. CPSign was compared against other regularly used methods for this task, using 32 benchmark datasets, demonstrating that CPSign produces predictive accuracy on par with the best performing methods.
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7. |
- Arvidsson McShane, Staffan, 1990-, et al.
(författare)
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CPSign : Conformal Prediction for Cheminformatics Modeling
- 2024
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Ingår i: Journal of Cheminformatics. - : BioMed Central (BMC). - 1758-2946. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Conformal prediction has seen many applications in pharmaceutical science, being able to calibrate outputs of machine learning models and producing valid prediction intervals. We here present the open source software CPSign that is a complete implementation of conformal prediction for cheminformatics modeling. CPSign implements inductive and transductive conformal prediction for classification and regression, and probabilistic prediction with the Venn-ABERS methodology. The main chemical representation is signatures but other types of descriptors are also supported. The main modeling methodology is support vector machines (SVMs), but additional modeling methods are supported via an extension mechanism, e.g. DeepLearning4J models. We also describe features for visualizing results from conformal models including calibration and efficiency plots, as well as features to publish predictive models as REST services. We compare CPSign against other common cheminformatics modeling approaches including random forest, and a directed message-passing neural network. The results show that CPSign produces robust predictive performance with comparative predictive efficiency, with superior runtime and lower hardware requirements compared to neural network based models. CPSign has been used in several studies and is in production-use in multiple organizations. The ability to work directly with chemical input files, perform descriptor calculation and modeling with SVM in the conformal prediction framework, with a single software package having a low footprint and fast execution time makes CPSign a convenient and yet flexible package for training, deploying, and predicting on chemical data. CPSign can be downloaded from GitHub at https://github.com/arosbio/cpsign.
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8. |
- Arvidsson, Staffan, et al.
(författare)
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Prediction of Metabolic Transformations using Cross Venn-ABERS Predictors
- 2017
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Ingår i: Conformal and Probabilistic Prediction with Applications (COPA) 2017. ; , s. 118-131
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Konferensbidrag (refereegranskat)abstract
- Prediction of drug metabolism is an important topic in the drug discovery process, and we here present a study using probabilistic predictions applying Cross Venn-ABERS Predictors (CVAPs) on data for site-of-metabolism. We used a dataset of 73599 biotransformations, applied SMIRKS to define biotransformations of interest and constructed five datasets where chemical structures were represented using signatures descriptors. The results show that CVAP produces well-calibrated predictions for all datasets with good predictive capability, making CVAP an interesting method for further exploration in drug discovery applications.
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9. |
- Bergek, Anna, 1973, et al.
(författare)
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Analysing the Dynamics and Fucntionality of Sectoral Innovation Systems - a manual
- 2005
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Ingår i: DRUID Tenth Anniversary Summer Conference 2005, Copenhagen Business School, Copenhagen, Denmark, June 27-29, 2005.
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Konferensbidrag (refereegranskat)abstract
- Various researchers and policy analysts have experimented with empirical studies of sectoral innovation systems (SIS), in which attempts have been made to understand the current structure of various innovation systems and trace their dynamics. We have captured the dynamics in terms of not only the structural components of a SIS but also pioneered such an analysis in terms of functional patterns (as well as functionality). In a collaborative work with VINNOVA (the Swedish Agency for Innovation Systems), we have taken the analysis one step further and made explicit a scheme of analysis, or a manual for policy makers. The manual is based on the received literature, our prior experience in developing and applying functional thinking and three experimental case studies, conducted in collaboration with VINNOVA. The manual can be used by policy makers to identify not only the key policy issues but also to set policy goals and to assess the usefulness of various policy instruments.
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