| 1. |
- Abel, Frida, 1974, et al.
(författare)
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A 6-gene signature identifies four molecular subgroups of neuroblastoma
- 2011
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Ingår i: Cancer Cell International. - : Springer Science and Business Media LLC. - 1475-2867. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p
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| 2. |
- Abtahi, Farhad, 1981-, et al.
(författare)
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Development and preliminary evaluation of an Android based heart rate variability biofeedback system
- 2014
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Ingår i: Engineering in Medicine and Biology Society (EMBC), 2014 36th Annual International Conference of the IEEE. - : IEEE. - 9781424479290 ; 2014, s. 3382-5
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Konferensbidrag (refereegranskat)abstract
- The reduced Heart Rate Variability (HRV) is believed to be associated with several diseases such as congestive heart failure, diabetes and chronic kidney diseases (CKD). In these cases, HRV biofeedback may be a potential intervention method to increase HRV which in turn is beneficial to these patients. In this work, a real-time Android biofeedback application based on a Bluetooth enabled ECG and thoracic electrical bioimpedance (respiration) measurement device has been developed. The system performance and usability have been evaluated in a brief study with eight healthy volunteers. The result demonstrates real-time performance of system and positive effects of biofeedback training session by increased HRV and reduced heart rate. Further development of the application and training protocol is ongoing to investigate duration of training session to find an optimum length and interval of biofeedback sessions to use in potential interventions.
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| 3. |
- Ahemaiti, Aikeremu, 1984, et al.
(författare)
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A multifunctional pipette for localized drug administration to brain slices
- 2013
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Ingår i: Journal of Neuroscience Methods. - : Elsevier BV. - 0165-0270 .- 1872-678X. ; 219:2, s. 292-296
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a superfusion method utilizing an open-volume microfluidic device for administration of pharmacologically active substances to selected areas in brain slices with high spatio-temporal resolution. The method consists of a hydrodynamically confined flow of the active chemical compound, which locally stimulates neurons in brain slices, applied in conjunction with electrophysiological recording techniques to analyze the response. The microfluidic device, which is a novel free-standing multifunctional pipette, allows diverse superfusion experiments, such as testing the effects of different concentrations of drugs or drug candidates on neurons in different cell layers with high positional accuracy, affecting only a small number of cells. We demonstrate herein the use of the method with electrophysiological recordings of pyramidal cells in hippocampal and prefrontal cortex brain slices from rats, determine the dependence of electric responses on the distance of the superfusion device from the recording site, document a multifold gain in solution exchange time as compared to whole slice perfusion, and show that the device is able to store and deliver up to four solutions in a series. Localized solution delivery by means of open-volume microfluidic technology also reduces reagent consumption and tissue culture expenses significantly, while allowing more data to be collected from a single tissue slice, thus reducing the number of laboratory animals to be sacrificed for a study. (C) 2013 Elsevier B.V. All rights reserved.
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| 4. |
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| 5. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
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Lopinavir/ritonavir, atazanavir/ritonavir, and efavirenz in antiretroviral-naïve HIV-1-infected individuals over 144 weeks: An open-label randomized controlled trial.
- 2013
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 45:7, s. 543-551
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Tidskriftsartikel (refereegranskat)abstract
- Background: The objective of this study was to compare the efficacy of ritonavir boosted atazanavir versus ritonavir boosted lopinavir or efavirenz, all in combination with 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs), over 144 weeks in antiretroviral-naïve HIV-1-infected individuals. Methods: A prospective open-label randomized controlled trial was conducted at 29 sites in Sweden and Norway between April 2004 and December 2009. Patients were randomized to receive either efavirenz 600 mg once daily (EFV), or atazanavir 300 mg and ritonavir 100 mg once daily (AZV/r), or lopinavir 400 mg and ritonavir 100 mg twice daily (LPV/r). The primary endpoints were the proportion of patients with HIV-1 RNA 100,000 copies/ml at baseline had similar response rates in all arms. Conclusion: EFV was superior to LPV/r at week 48, but there were no significant differences between the 3 arms in the long-term (144 weeks) follow-up.
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| 6. |
- Angeria, Maria, et al.
(författare)
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Experimental Animal Models for Studies on the Mechanisms of Blast-induced Neurotrauma
- 2012
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 3:30
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Tidskriftsartikel (refereegranskat)abstract
- A blast injury is a complex type of physical trauma resulting from the detonation of explosive compounds and has become an important issue due to the use of improvised explosive devices (IED) in current military conflicts. Blast-induced neurotrauma (BINT) is a major concern in contemporary military medicine and includes a variety of injuries that range from mild to lethal. Extreme forces and their complex propagation characterize BINT. Modern body protection and the development of armored military vehicles can be assumed to have changed the outcome of BINT. Primary blast injuries are caused by overpressure waves whereas secondary, tertiary, and quaternary blast injuries can have more varied origins such as the impact of fragments, abnormal movements, or heat. The characteristics of the blast wave can be assumed to be significantly different in open field detonations compared to explosions in a confined space, such an armored vehicle. Important parameters include peak pressure, duration, and shape of the pulse. Reflections from walls and armor can make the prediction of effects in individual cases very complex. Epidemiological data do not contain information of the comparative importance of the different blast mechanisms. It is therefore important to generate data in carefully designed animal models. Such models can be selective reproductions of a primary blast, penetrating injuries from fragments, acceleration movements, or combinations of such mechanisms. It is of crucial importance that the physical parameters of the employed models are well characterized so that the experiments can be reproduced in different laboratory settings. Ideally, pressure recordings should be calibrated by using the same equipment in several laboratories. With carefully designed models and thoroughly evaluated animal data it should be possible to achieve a translation of data between animal and clinical data. Imaging and computer simulation represent a possible link between experiments and studies of human cases. However, in order for mathematical simulations to be completely useful, the predictions will most likely have to be validated by detailed data from animal experiments. Some aspects of BINT can conceivably be studied in vitro. However, factors such as systemic response, brain edema, inflammation, vasospasm, or changes in synaptic transmission and behavior must be evaluated in experimental animals. Against this background, it is necessary that such animal experiments are carefully developed imitations of actual components in the blast injury. This paper describes and discusses examples of different designs of experimental models relevant to BINT.
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| 7. |
- Annerbrink, Kristina, 1974, et al.
(författare)
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Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and monoamine metabolite concentrations in cerebrospinal fluid
- 2010
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Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 179:2, s. 231-234
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II has been suggested to influence central dopamine and serotonin turnover. Since the angiotensin-converting enzyme (ACE) plays a key role in angiotensin regulation by converting inactive angiotensin 1 to active angiotensin II, we hypothesised that the functional insertion/deletion (I/D) polymorphism in the ACE gene, which has previously been suggested to be associated with, depression and panic disorder, may influence monoamine activity. A well-established technique for assessing brain monoamine turnover in humans is to measure concentrations of monoamine metabolites in the cerebrospinal fluid (CSF). We thus investigated possible associations between the ACE I/D polymorphism and CSF monoamine metabolite concentrations in a population of healthy male subjects. After having found such an association between the ACE I/D polymorphism and CSF levels of the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid in this sample, I carriers displaying lower levels, we tried to replicate this observation in a population of violent male offenders from which also both CSF and DNA were available. Also in this sample, the same associations were found. Our results suggest that the ACE I/D polymorphism may play a role in the modulation of serotonergic and dopaminergic turnover in men. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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| 8. |
- Asadzadeh, Mohammad, 1952, et al.
(författare)
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Galerkin methods for primary ion transport in inhomogeneous media
- 2010
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Ingår i: Kinetic and Related Models. - : American Institute of Mathematical Sciences (AIMS). - 1937-5093 .- 1937-5077. ; 3:3, s. 373-394
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Tidskriftsartikel (refereegranskat)abstract
- This paper concerns the energy deposition of high-energy (e.g., approximate to 50 - 500 MeV) proton and carbon ions and high-energy electrons (of approximate to 50 MeV), in inhomogeneous media. Our goal is to develop a flexible model incorporated with the analytic theory for ions based on bipartition and Fokker-Planck developments. Both procedures are leading to convection dominated convection diffusion equations. We study convergence for semi-discrete and fully discrete approximations of a such obtained equation, for abroad beam model, using the standard Galerkin and streamline diffusion finite element methods. The analytic broad beam model of the light ion absorbed dose were compared with the results of the modified Monte Carlo (MC) code SHIELD-HIT+ and those of Galerkin streamline diffusion approach.
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| 9. |
- Asadzadeh, Mohammad, 1952, et al.
(författare)
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Ion transport in inhomogeneous media based on the bipartition model for primary ions
- 2010
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Ingår i: Computers & Mathematics with Applications. - : Elsevier BV. - 0898-1221. ; 60:8, s. 2445-2459
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Tidskriftsartikel (refereegranskat)abstract
- The present paper is focused on the mathematical modeling of the charged particle transport in nonuniform media. We study the energy deposition of high energy protons and electrons in an energy range of approximate to 50-500 MeV. This work is an extension of the bipartition model; for high energy electrons studied by Luo and Brahme in [Z. Luo, A. Brahme, High energy electron transport, Phys. Rev. B 46 (1992) 739-752] [42]; and for light ions studied by Luo and Wang in [Z. Luo, S. Wang, Bipartition model of ion transport: an outline of new range theory for light ions, Phys. Rev. B 36 (1987) 1885-1893]; to the field of high energy ions in inhomogeneous media with the retained energy-loss straggling term. In the bipartition model, the transport equation is split into a coupled system of convection diffusion equations controlled by a partition condition. A similar split is obtained in an asymptotic expansion approach applied to the linear transport equation yielding pencil beam and broad beam models, which are again convection diffusion type equations. We shall focus on the bipartition model applied for solving three types of problems: (i) normally incident ion transport in a slab; (ii) obliquely incident ion transport in a semi-infinite medium; (iii) energy deposition of ions in a multilayer medium. The broad beam model of the proton absorbed dose was illustrated with the results of a modified Monte Carlo code: SHIELD - HIT+.
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| 10. |
- Berg, Tove, et al.
(författare)
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Gene expression analysis of membrane transporters and drug-metabolizing enzymes in the lung of healthy and COPD subjects.
- 2014
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Ingår i: Pharmacology research & perspectives. - : Wiley. - 2052-1707. ; 2:4, s. e00054-
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Tidskriftsartikel (refereegranskat)abstract
- This study describes for the first time the expression levels of genes encoding membrane transporters and drug-metabolizing enzymes in the lungs of ex-smoking patients with chronic obstructive pulmonary disease (COPD). Membrane transporters and drug-metabolizing enzymes are key determinants of drug uptake, metabolism, and elimination for systemically administered as well as inhaled drugs, with consequent influence on clinical efficacy and patient safety. In this study, while no difference in gene expression was found between healthy and COPD subjects, we identified a significant regional difference in mRNA expression of both membrane transporters and drug-metabolizing enzymes between central and peripheral tissue in both healthy and COPD subjects. The majority of the differentially expressed genes were higher expressed in the central airways such as the transporters SLC2A1 (GLUT1), SLC28A3 (CNT3), and SLC22A4 (OCTN1) and the drug-metabolizing enzymes GSTZ1, GSTO2, and CYP2F1. Together, this increased knowledge of local pharmacokinetics in diseased and normal lung may improve modeling of clinical outcomes of new chemical entities intended for inhalation therapy delivered to COPD patients. In addition, based on the similarities between COPD and healthy subjects regarding gene expression of membrane transporters and drug-metabolizing enzymes, our results suggest that clinical pharmacological studies in healthy volunteers could be a valid model of COPD patients regarding drug disposition of inhaled drugs in terms of drug metabolism and drug transporters.
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