| 1. |
- Johansson, Lovisa, et al.
(författare)
-
Genetic variance in the adiponutrin gene family and childhood obesity.
- 2009
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:4
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: The adiponutrin gene family consists of five genes (PNPLA1-5) coding for proteins with both lipolytic and lipogenic properties. PNPLA3 has previously been associated with adult obesity. Here we investigated the possible association between genetic variants in these genes and childhood and adolescent obesity. METHODS/RESULTS: Polymorphisms in the five genes of the adiponutrin gene family were selected and genotyped using the Sequenom platform in a childhood and adolescent obesity case-control study. Six variants in PNPLA1 showed association with obesity (rs9380559, rs12212459, rs1467912, rs4713951, rs10947600, and rs12199580, p<0.05 after adjustment for age and gender). Three variants in PNPLA3 showed association with obesity before, but not after, adjustment for age and gender (rs139051, rs12483959, and rs2072907, p>0.05). When analyzing these SNPs in relation to phenotypes, two SNPs in the PNPLA3 gene showed association with insulin sensitivity (rs12483959: beta = -0.053, p = 0.016, and rs2072907: beta = -0.049, p = 0.024). No associations were seen for PNPLA2, PNPLA4, and PNPLA5. CONCLUSIONS: Genetic variation in the adiponutrin gene family does not seem to contribute strongly to obesity in children and adolescents. PNPLA1 exhibited a modest effect on obesity and PNPLA3 on insulin sensitivity. These data, however, require confirmation in other cohorts and ethnic groups.
|
|
| 2. |
- Rydberg Sterner, Therese, et al.
(författare)
-
The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.
- 2019
-
Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209
-
Tidskriftsartikel (refereegranskat)abstract
- To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n=1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
|
|
| 3. |
- Gad, Helge, et al.
(författare)
-
MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
-
Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
|
|
| 4. |
- Rasmussen, Eva Rye, et al.
(författare)
-
Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment.
- 2020
-
Ingår i: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 20:6, s. 770-783
-
Tidskriftsartikel (refereegranskat)abstract
- Angioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 × 10-5). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 × 10-8). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05-2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi- and ARB-induced angioedema.
|
|
| 5. |
- Sloboda, Tamara, et al.
(författare)
-
A method for studying pico to microsecond time-resolved core-level spectroscopy used to investigate electron dynamics in quantum dots
- 2020
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Time-resolved photoelectron spectroscopy can give insights into carrier dynamics and offers the possibility of element and site-specific information through the measurements of core levels. In this paper, we demonstrate that this method can access electrons dynamics in PbS quantum dots over a wide time window spanning from pico- to microseconds in a single experiment carried out at the synchrotron facility BESSY II. The method is sensitive to small changes in core level positions. Fast measurements at low pump fluences are enabled by the use of a pump laser at a lower repetition frequency than the repetition frequency of the X-ray pulses used to probe the core level electrons: Through the use of a time-resolved spectrometer, time-dependent analysis of data from all synchrotron pulses is possible. Furthermore, by picosecond control of the pump laser arrival at the sample relative to the X-ray pulses, a time-resolution limited only by the length of the X-ray pulses is achieved. Using this method, we studied the charge dynamics in thin film samples of PbS quantum dots on n-type MgZnO substrates through time-resolved measurements of the Pb 5d core level. We found a time-resolved core level shift, which we could assign to electron injection and charge accumulation at the MgZnO/PbS quantum dots interface. This assignment was confirmed through the measurement of PbS films with different thicknesses. Our results therefore give insight into the magnitude of the photovoltage generated specifically at the MgZnO/PbS interface and into the timescale of charge transport and electron injection, as well as into the timescale of charge recombination at this interface. It is a unique feature of our method that the timescale of both these processes can be accessed in a single experiment and investigated for a specific interface.
|
|
| 6. |
- Andersen, Paul Krüger, et al.
(författare)
-
Response to the Proposal for a Directive on Corporate Sustainability Due Diligence by Nordic and Baltic Company Law Scholars
- 2022
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- On February 23, 2022, The EU Commission published its Proposal for a Directive of the European Parliament and of the Council on Corporate Sustainability Due Diligence and amending Directive (EU) 2019/1937 (“CSDDD” or “the Proposal”). The purpose of the Proposal, to further the “Union’s transition to a climate-neutral and green economy in line with the European Green Deal and in delivering on the UN Sustainable Development Goals”, is of great importance, and the Commission’s initiative is therefore commendable. However, it is our firm opinion that the Proposal should not be enacted in its present form, and that if it were to be, it would not only damage European businesses but also run the risk of having an adverse effect on both the transition to a climate-neutral economy as well as the goal of delivering on the UN Sustainable Development Goals. This is to a large extent because many of the Proposal’s provisions are excessive, unfounded and disproportionate and as such in violation of the fundamental principles of subsidiarity and proportionality safeguarded by Art. 5 TEU as well as having a questionable basis in Art. 50 TFEU. Furthermore and in regard of procedure, we find that the presentation of the Proposal by the Commission represents a disregard for the principles of better regulation that should not pass unnoticed and must be observed in the future to maintain trust in the legislative process of the Union.In this response to the consultation, we have presented an analysis of the key issues of the Proposal from a corporate governance perspective. We have divided the response into two parts: one on the pure corporate governance parts of the Proposal (article 15, 25 and 26) and one of the due diligence parts of the Proposal. With regards to the corporate governance parts of the Proposal, our conclusion is that they, by and large, should not be included in the proposed directive at all. Including them would in several ways be in breach of the EU principles on subsidiarity and proportionality, but perhaps more importantly, they are not only unsubstantiated by available empirical evidence on corporate behaviour, but also refuted by what we know. There is also good reason to believe that the proposed rules on director’s duties and environmental remuneration would risk decreasing the effectiveness of the stock markets within the EU contrary to the goal of a Capital Market Union, which also risk slowing down the necessary transition to a green economy and the goals of the EU Green Deal. The regulation necessary for the Capital Market Union and the EU Green Deal should complement each other, not collide as would be the outcome if the Proposal is adopted in its present form.With regards to the due diligence parts of the Proposal, our criticism is limited to corporate governance aspects and far less fundamental. We primarily believe that grounds for harmonisation needs further consideration in the present very challenging times, that Article 22 on Civil Liability might in several ways be counter-productive to the goals of the Proposal, that the effects on SMEs as well as for the financial companies included covered by the Proposal warrants further analysis, that the choice to focus the Proposal on individual companies instead of company groups needs to be reviewed, and that a risk based approach should be taken rather than an approach were companies are unable to focus their efforts to where they can be most effective. Overall, these issues can be worked out, but if they are not, then the proposed directive would not only have a severe adverse impact on EU companies and possibly capital markets, but might actually hinder EU companies from acting in the way that the Proposal aims for them to do.This joint response to the public consultation is made by a group of Nordic and Baltic company law scholars who, although we may not agree on every detail, do share the main arguments and grave concerns expressed here.
|
|
| 7. |
- Andersson, Jeanette, 1968-
(författare)
-
Omsorgsplikt och god sed i avtal om shipmanagement
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Under Swedish law a service provider’s performance is pervaded by a duty of care (Swe: omsorgsplikt). The study deals with the meaning and significance of the duty of care in a ship management contract under which a shipmanager undertakes to carry out one or several management services in respect of the vessel as agents for and on behalf of a shipowner. The study is mainly focused on the shipmanager’s duty of care and duty to perform the management services in accordance with sound ship management practice as set out in the standard ship management agreement SHIPMAN 2009.The first aim of the study is to analyze and systematize the shipmanager’s duty of care in a ship management agreement. The second aim of the study is to analyze what it means to provide management services in accordance with sound ship management practice. Thirdly, the shipmanager’s duty of care is examined in relation to a service provider’s general duty of care in long term commercial relationships. To achieve these aims, a number of research questions are examined, namely:Regarding the meaning and extent of a shipmanager’s duty of care: What is the relevance and meaning of a service provider’s duties to act in accordance with the mandate and in the interest of the client, to follow the client’s directions, to perform the service professionally, to act with care when choosing a counterparty to the prospective contract, to take good care of the client’s property, and to give account for the services?Regarding the question of sound ship management practice: How does the shipmanager’s duty of care differ from the duty to perform the management services in accordance with sound ship management? Which duties to act with care and in accordancewith sound ship management practice could be required from the shipmanager as regards specific ship management processes such as the vessel operating budget, the vessel operating report, and the use of safety and quality management systems.In addition, the sanctions and legal consequences of a breach of the duty of care are analyzed briefly.The study is based on a problem- and interestoriented methodological approach with teleological considerations and weighing of different interests. Also, the study of the meaning and significance of the shipmanager’s duty of care includes certain internal as well as external comparative elements. A number of different theories of the duty of care are examined and analyzed.The conclusions of the study are summarised in Chapter 8. One general conclusion is that the shipmanager’s duty of care and duty to perform the management services in accordance with sound ship management practice could be viewed and serve as a management control function towards the interests of the contractual promise, the contractual relationship as well as the interest of sustainability respectively.
|
|
| 8. |
- Andersson, Martin, et al.
(författare)
-
Tionde konferensen om SoC
- 2010
-
Ingår i: Elektronik i Norden. - 1103-2944. ; , s. 32-32
-
Tidskriftsartikel (populärvet., debatt m.m.)
|
|
| 9. |
|
|
| 10. |
- Andersson, Sten, et al.
(författare)
-
Aktiebolagslagen - En kommentar. Del 1-3, med supplement 9
- 2014
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- Lagen kommenteras utförligt paragraf för paragraf. Den nya lagen innehåller både sakliga och redaktionella ändringa, bl.a. reglerna om bolagsbildning, som utformats för att bättre överensstämma med hur bolagsbildning i praktiken går till, nya bestämmelser för samtyckes- och förköpsförbehåll, ett särskilt system för fullmaktsinsamling samt en mer enhetlig utformning av bestämmelserna om olika slag av värdeöverföringar från bolaget.
|
|
| 11. |
|
|
| 12. |
- Backström, Tobias, et al.
(författare)
-
CRF and urotensin I effects on aggression and anxiety-like behavior in rainbow trout
- 2011
-
Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 214:6, s. 907-914
-
Tidskriftsartikel (refereegranskat)abstract
- Corticotropin-releasing factor (CRF) is central in the stress response but also modulates several behaviors including anxiety-related behaviors and aggression. In this study, juvenile rainbow trout (Oncorhynchus mykiss) were tested for competitive ability, determined during dyadic fights for dominance, after intracerebroventricular (i.c.v.) administration of CRF, urotensin I (UI), the non-specific CRF antagonist alpha-helical RF9-41 (ahCRF) or the CRF receptor subtype 1-specific antagonist antalarmin, when paired with a mass-matched con-specific injected with saline. In addition, isolated fish received the same substances. Plasma cortisol and brain monoamines were monitored in all fish. Most fish receiving CRF showed a conspicuous behavior consisting of flaring the opercula, opening the mouth and violent shaking of the head from side to side. When this occurred, the fish immediately forfeited the fight. Similar behavior was observed in most fish receiving UI but no effect on outcome of dyadic fights was noted. This behavior seems similar to non-ambulatory motor activity seen in rats and could be anxiety related. Furthermore, fish receiving CRF at a dose of 1000. ng became subordinate, whereas all other treatments had no effects on the outcome of dyadic fights. In addition, isolated fish receiving ahCRF had lower brain stem concentrations of 5-hydroxyindoleacetic acid, serotonin, 3,4-dihydroxyphenylacetic acid and dopamine. In conclusion, CRF seems to attenuate competitive ability, and both CRF and UI seem to induce anxiety-like behavior.
|
|
| 13. |
|
|
| 14. |
- Bjorklund, Svante, et al.
(författare)
-
Target Classification in Perimeter Protection with a Micro-Doppler Radar
- 2016
-
Ingår i: 2016 17TH INTERNATIONAL RADAR SYMPOSIUM (IRS). - 9781509025183
-
Konferensbidrag (refereegranskat)abstract
- In security surveillance at the perimeter of critical infrastructure, such as airports and power plants, approaching objects have to be detected and classified. Especially important is to distinguish between humans, animals and vehicles. In this paper, micro-Doppler data (from movement of internal parts of the target) have been collected with a small radar of a low complexity and cost-effective type. From time-velocity diagrams of the data, some physical features have been extracted and used in a support vector machine classifier to distinguish between the classes "human", "animal" and "man-made object". Both the type of radar and the classes are suitable for perimeter protection. The classification result are rather good, 77% correct classification. Particularly interesting is the surprisingly good ability to distinguish between humans and animals. This also indicates that we can choose to have limitations in the radar and still solve the classification task.
|
|
| 15. |
- Cai, Xing Shi, et al.
(författare)
-
Inversions in Split Trees and Conditional Galton-Watson Treest
- 2019
-
Ingår i: Combinatorics, probability & computing. - 0963-5483 .- 1469-2163. ; 28:3, s. 335-364
-
Tidskriftsartikel (refereegranskat)abstract
- We study I(T), the number of inversions in a tree T with its vertices labelled uniformly at random, which is a generalization of inversions in permutations. We first show that the cumulants of I(T) have explicit formulas involving the k-total common ancestors of T (an extension of the total path length). Then we consider X-n, the normalized version of I(T-n), for a sequence of trees T-n. For fixed T-n's, we prove a sufficient condition for X-n to converge in distribution. As an application, we identify the limit of X-n for complete b-ary trees. For T(n )being split trees [16], we show that X-n converges to the unique solution of a distributional equation. Finally, when T-n's are conditional Galton-Watson trees, we show that X-n converges to a random variable defined in terms of Brownian excursions. By exploiting the connection between inversions and the total path length, we are able to give results that significantly strengthen and broaden previous work by Panholzer and Seitz [46].
|
|
| 16. |
|
|
| 17. |
- Cappel, Ute B, et al.
(författare)
-
Electronic structure dynamics in a low bandgap polymer studied by time-resolved photoelectron spectroscopy.
- 2016
-
Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 18:31, s. 21921-9
-
Tidskriftsartikel (refereegranskat)abstract
- Means to measure the temporal evolution following a photo-excitation in conjugated polymers are a key for the understanding and optimization of their function in applications such as organic solar cells. In this paper we study the electronic structure dynamics by direct pump-probe measurements of the excited electrons in such materials. Specifically, we carried out a time-resolved photoelectron spectroscopy (TRPES) study of the polymer PCPDTBT by combining an extreme ultraviolet (XUV) high harmonic generation source with a time-of-flight spectrometer. After excitation to either the 1st excited state or to a higher excited state, we follow how the electronic structure develops and relaxes on the electron binding energy scale. Specifically, we follow a less than 50 fs relaxation of the higher exited state and a 10 times slower relaxation of the 1st excited state. We corroborate the results using DFT calculations. Our study demonstrates the power of TRPES for studying photo-excited electron energetics and dynamics of solar cell materials.
|
|
| 18. |
- Cappel, Ute B, et al.
(författare)
-
Partially Reversible Photoinduced Chemical Changes in a Mixed-Ion Perovskite Material for Solar Cells.
- 2017
-
Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 9:40, s. 34970-34978
-
Tidskriftsartikel (refereegranskat)abstract
- ) with the element specificity and chemical sensitivity of core-level photoelectron spectroscopy. By carrying out measurements at a synchrotron beamline optimized for low X-ray fluxes, we are able to avoid sample changes due to X-ray illumination and are therefore able to monitor what sample changes are induced by visible illumination only. We find that laser illumination causes partially reversible chemistry in the surface region, including enrichment of bromide at the surface, which could be related to a phase separation into bromide- and iodide-rich phases. We also observe a partially reversible formation of metallic lead in the perovskite structure. These processes occur on the time scale of minutes during illumination. The presented methodology has a large potential for understanding light-induced chemistry in photoactive materials and could specifically be extended to systematically study the impact of morphology and composition on the photostability of metal halide perovskites.
|
|
| 19. |
- Carlander, Johan, et al.
(författare)
-
Risk of Complications with Energy-Based Surgical Devices in Thyroid Surgery : A National Multicenter Register Study
- 2016
-
Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 40:1, s. 117-123
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundEnergy-based surgical devices (EBD) combining cutting and coagulation are increasingly used in thyroid surgery. However, there is a lack of information about potential benefits and risk of complications outside controlled trials. The aims of this national multicenter register study were to describe the use of EDB, their potential effect on complication rates, and on operation time.Materials and methodsThe Scandinavian Quality Register for Thyroid and Parathyroid surgery includes 35 surgical units in Sweden and covered 88 % of the thyroid procedures performed during 2008–2009. The use of the EBD was specifically registered for 12 months, and 1297 patients were included. Surgically related complications and operation time were evaluated. The clamp-and-tie group (C-A-T) constituted the control group for comparison with procedures where EBD was used.ResultsThe thyroid procedures performed included C-A-T (16.6 %), bipolar electrosurgery (ES: 56.5 %), electronic vessel sealing (EVS: 12.2 %), and ultrasonic dissection (UD: 14.5 %). Mean operative time was longer with EVS (p < 0.001) and shorter with UD (p < 0.05) than in the other groups. The bipolar ES group and the EVS group had higher incidence of calcium treatment at discharge and after 6 weeks than the UD group. No significant difference in nerve injury was found between the groups. There was a significant more frequent use of topical hemostatic agents in the EBD group compared to C-A-T.ConclusionIn this national multicenter study, the use of UD shortened and EVS increased operating time. There was a higher risk of calcium treatment at discharge and after 6 weeks after use of EVS and bipolar ES than after UD use. There was a significant more frequent use of topical hemostatic agents in the EBD groups compared to C-A-T.
|
|
| 20. |
- Eriksson, Lennart, et al.
(författare)
-
GIFI-PLS: Modeling of Non-Linearities and Discontinuities in QSAR
- 2000
-
Ingår i: QSAR. ; 19:4, s. 345-55
-
Tidskriftsartikel (refereegranskat)abstract
- This paper introduces to the QSAR community a novel method for modeling and understanding non-linear relationships between biological potency and chemical structure properties of molecules. The approach, GIFI-PLS, is based on ``binning'' of quantitative X-variables into categorical variables. Each categorical variable is then expanded into a set of linked 1/0 dummy variables, which enable modeling of non-linearity. By way of four QSAR data sets, it is demonstrated that GIFI-PLS is useful for modeling of non-linearity and discontinuity in QSAR, and that the predictive power of a QSAR model may improve.
|
|
| 21. |
- Eriksson, Lennart, et al.
(författare)
-
Megavariate analysis of hierarchical QSAR data
- 2002
-
Ingår i: Journal of Computer-Aided Molecular Design. ; 16:10, s. 711-26
-
Tidskriftsartikel (refereegranskat)abstract
- Multivariate PCA- and PLS-models involving many variables are often difficult to interpret, because plots and lists of loadings, coefficients, VIPs, etc, rapidly become messy and hard to overview. There may then be a strong temptation to eliminate variables to obtain a smaller data set. Such a reduction of variables, however, often removes information and makes the modelling efforts less reliable. Model interpretation may be misleading and predictive power may deteriorate.A better alternative is usually to partition the variables into blocks of logically related variables and apply hierarchical data analysis. Such blocked data may be analyzed by PCA and PLS. This modelling forms the base-level of the hierarchical modelling set-up. On the base-level in-depth information is extracted for the different blocks. The score vectors formed on the base-level, here called `super variables', may be linked together in new matrices on the top-level. On the top-level superficial relationships between the X- and the Y-data are investigated.In this paper the basic principles of hierarchical modelling by means of PCA and PLS are reviewed. One objective of the paper is to disseminate this concept to a broader QSAR audience. The hierarchical methods are used to analyze a set of 10 haloalkanes for which K = 30 chemical descriptors and M = 255 biological responses have been gathered. Due to the complexity of the biological data, they are sub-divided in four blocks. All the modelling steps on the base-level and the top-level are reported and the final QSAR model is interpreted thoroughly.
|
|
| 22. |
- Eriksson, Lennart, et al.
(författare)
-
Multi- and Megavariate Data Analysis : Part II: Advanced Applications and Method Extensions
- 2006
-
Bok (refereegranskat)abstract
- This second volume has two parts, the first with specialized applications of multi- and mega-variate analysis, namely:QSAR (quantitative structure-activity relationships) describes how series of molecular structures can be translated to quantitative data and how these data then are used to model and predict biological activity measurements made on the corresponding molecules. Chapters on how the QSAR concept applies in peptide QSAR, lead finding and optimization, combinatorial chemistry, and chem-and bio-informatics, are included.The multi- and megavariate analysis of “omics” data, has a special chapter, i.e., data from metabonomics, proteomics, genomics and other areas.Then follow six chapters on extensions of the basic projection methods (PCA and PLS):Orthogonal PLS (OPLS) showing how a PLS model can be “rotated” so that all y-related information appears in the first component, which facilitates the model interpretation.Hierarchical modeling, both PC and PLS, allowing variables of different types to be handled in separate blocks, which greatly simplifies the handling of datasets with very many variables.Non-linear PLS describes various approaches to the modeling of non-linear relationships between predictors X and responses Y.The Image Analysis chapter shows how multivariate analysis applies to the analysis of series of digital images.Data Mining and Integration has a discussion of how to get useful information out of large and complicated data sets, and how to manage and organize data in complex investigations.The second volume ends with a chapter on preference and sensory data, followed by an appendix summarizing the multivariate approach, statistical notes, and references.
|
|
| 23. |
- Eriksson, Lennart, et al.
(författare)
-
On the selection of the training set in environmental QSAR analysis when compounds are clustered
- 2000
-
Ingår i: Journal of Chemometrics. ; 14:5-6, s. 599-616
-
Tidskriftsartikel (refereegranskat)abstract
- In QSAR analysis in environmental sciences, adverse effects of chemicals released to the environment are modelled and predicted as a function of the chemical properties of the pollutants. Usually the set of compounds under study contains several classes of substances, i.e. a more or less strongly clustered set. It is then needed to ensure that the selected training set comprises compounds representing all those chemical classes. Multivariate design in the principal properties of the compound classes is usually appropriate for selecting a meaningful training set. However, with clustered data, often seen in environmental chemistry and toxicology, a single multivariate design may be suboptimal because of the risk of ignoring small classes with few members and only selecting training set compounds from the largest classes. Recently a procedure for training set selection recognizing clustering was proposed by us. In this approach, when non-selective biological or environmental responses are modelled, local multivariate designs are constructed within each cluster (class). The chosen compounds arising from the local designs are finally united in the overall training set, which thus will contain members from all clusters. The proposed strategy is here further tested and elaborated by applying it to a series of 351 chemical substances for which the soil sorption coefficient is available. These compounds are divided into 14 classes containing between 10 and 52 members. The training set selection is discussed, followed by multivariate QSAR modelling, model interpretation and predictions for the test set. Various types of statistical experimental designs are tested during the training set selection phase.
|
|
| 24. |
- Eriksson, Lennart, et al.
(författare)
-
Orthogonal signal correction, wavelet analysis, and multivariate calibration of complicated process fluorescence data
- 2000
-
Ingår i: Analytica Chimica Acta. ; 420:2, s. 181-95
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper, multivariate calibration of complicated process fluorescence data is presented. Two data sets related to the production of white sugar are investigated. The first data set comprises 106 observations and 571 spectral variables, and the second data set 268 observations and 3997 spectral variables. In both applications, a single response, ash content, is modelled and predicted as a function of the spectral variables. Both data sets contain certain features making multivariate calibration efforts non-trivial. The objective is to show how principal component analysis (PCA) and partial least squares (PLS) regression can be used to overview the data sets and to establish predictively sound regression models. It is shown how a recently developed technique for signal filtering, orthogonal signal correction (OSC), can be applied in multivariate calibration to enhance predictive power. In addition, signal compression is tested on the larger data set using wavelet analysis. It is demonstrated that a compression down to 4% of the original matrix size - in the variable direction - is possible without loss of predictive power. It is concluded that the combination of OSC for pre-processing and wavelet analysis for compression of spectral data is promising for future use.
|
|
| 25. |
- Eriksson, Lennart, et al.
(författare)
-
Separating Y-predictive and Y-orthogonal variation in multi-block spectral data
- 2006
-
Ingår i: Journal of Chemometrics. - : Wiley. - 0886-9383 .- 1099-128X. ; 20, s. 352-61
-
Tidskriftsartikel (refereegranskat)abstract
- Spectral data (X) may contain (a) variation that is correlated to concentrations or properties (Y) of samples and (b) variation that is unrelated to the same Y. This paper outlines an approach by which both such sources of variation may be resolved. The approach is based on a combination of hierarchical modelling and orthogonal partial least squares (OPLS). OPLS is first used at the base hierarchical level. The output is a labelling of the resulting score vectors as representing Y-predictive or Y-orthogonal variation. OPLS is then also used at the top hierarchical level together with principal components analysis (PCA). With PCA the Y-orthogonal X-variation is analysed and interpreted. With OPLS the Y-predictive X-variation is examined. The applicability of the proposed strategy is illustrated using one multi-block spectral data set.
|
|
