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| 2. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 3. |
- Kerzenmacher, T., et al.
(författare)
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Validation of NO2 and NO from the Atmospheric Chemistry Experiment (ACE)
- 2008
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 8:19, s. 5801--5841-
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Tidskriftsartikel (refereegranskat)abstract
- Vertical profiles of NO2 and NO have been obtained from solar occultation measurements by the Atmospheric Chemistry Experiment (ACE), using an infrared Fourier Transform Spectrometer (ACE-FTS) and (for NO2) an ultraviolet-visible-near-infrared spectrometer, MAESTRO (Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation). In this paper, the quality of the ACE-FTS version 2.2 NO2 and NO and the MAESTRO version 1.2 NO2 data are assessed using other solar occultation measurements (HALOE, SAGE II, SAGE III, POAM III, SCIAMACHY), stellar occultation measurements (GOMOS), limb measurements (MIPAS, OSIRIS), nadir measurements (SCIAMACHY), balloon-borne measurements (SPIRALE, SAOZ) and ground-based measurements (UV-VIS, FTIR). Time differences between the comparison measurements were reduced using either a tight coincidence criterion, or where possible, chemical box models. ACE-FTS NO2 and NO and the MAESTRO NO2 are generally consistent with the correlative data. The ACE-FTS and MAESTRO NO2 volume mixing ratio (VMR) profiles agree with the profiles from other satellite data sets to within about 20% between 25 and 40 km, with the exception of MIPAS ESA (for ACE-FTS) and SAGE II (for ACE-FTS (sunrise) and MAESTRO) and suggest a negative bias between 23 and 40 km of about 10%. MAESTRO reports larger VMR values than the ACE-FTS. In comparisons with HALOE, ACE-FTS NO VMRs typically (on average) agree to ±8% from 22 to 64 km and to +10% from 93 to 105 km, with maxima of 21% and 36%, respectively. Partial column comparisons for NO2 show that there is quite good agreement between the ACE instruments and the FTIRs, with a mean difference of +7.3% for ACE-FTS and +12.8% for MAESTRO.
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| 4. |
- Adamus-Górka, Magdalena, 1977-
(författare)
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Improved dose response modeling for normal tissue damage and therapy optimization
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present thesis is focused on the development and application of dose response models for radiation therapy. Radiobiological models of tissue response to radiation are an integral part of the radiotherapeutic process and a powerful tool to optimize tumor control and minimize damage to healthy tissues for use in clinical trials. Ideally, the models could work as a historical control arm of a clinical trial eliminating the need to randomize patents to suboptimal therapies. In the thesis overview part, some of the basic properties of the dose response relation are reviewed and the most common radiobiological dose-response models are compared with regard to their ability to describe experimental dose response data for rat spinal cord using the maximum likelihood method. For vascular damage the relative seriality model was clearly superior to the other models, whereas for white matter necrosis all models were quite good except possibly the inverse tumor and critical element models. The radiation sensitivity, seriality and steepness of the dose-response relation of the spinal cord is found to vary considerably along its length. The cervical region is more radiation sensitive, more parallel, expressing much steeper dose-response relation and more volume dependent probability of inducing radiation myelitis than the thoracic part. The higher number of functional subunits (FSUs) consistent with a higher amount of white matter close to the brain may be responsible for these phenomena. With strongly heterogeneous dose delivery and due to the random location of FSUs, the effective size of the FSU and the mean dose deposited in it are of key importance and the radiation sensitivity distribution of the FSU may be an even better descriptor for the response of the organ. An individual optimization of a radiation treatment has the potential to increase the therapeutic window and improve cure for a subgroup of patients.
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| 5. |
- Brocki, Karin C., et al.
(författare)
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Working memory in school-aged children with attention-deficit/hyperactivity disorder combined type : Are deficits modality specific and are they independent of impaired inhibitory control?
- 2008
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Ingår i: Journal of Clinical and Experimental Neuropsychology. - : Informa UK Limited. - 1380-3395 .- 1744-411X. ; 30:7, s. 749-759
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Tidskriftsartikel (refereegranskat)abstract
- This study examines differences between children with attention-deficit/ hyperactivity disorder combined type (ADHD-C) and normal controls on verbal and visuospatial working-memory (WM) tasks. The extent to which WM deficits in children with ADHD-C are independent of impaired inhibitory control was also examined. Two groups of 7- to 12-year-old boys participated in this study. The first group included 31 boys diagnosed with ADHD-C, and the second group included 34 boys without ADHD. Various verbal and visuospatial WM tasks and two inhibitory control tasksprepotent response inhibition and interference controlwere used. Overall, our results suggest impaired verbal and visuospatial WM processes in children with ADHD-C, as well as a lower level of performance on prepotent response inhibition. WM deficits in ADHD have previously been suggested to be particularly salient in the spatial domain, our results instead showed the largest effect for a verbal WM task thought to put heavy load on the executive or attentional control component of the WM system. An interpretation of this finding is that it is variation in terms of difficulty level or load on the executive WM processes, rather than variation in modality (verbal versus visuospatial), that is important in demonstrating WM deficits in ADHD-C. Finally, findings from logistic regression analyses showed that deficits in WM and inhibitory control seem to be semi-independent in children with ADHD-C, at least with regard to the elementary school age.
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| 6. |
- Carleer, M. R., et al.
(författare)
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Validation of water vapour profiles from the Atmospheric Chemistry Experiment (ACE)
- 2008
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Ingår i: Atmospheric Chemistry and Physics Discussion: An Interactive Open Access Journal of the European Geosciences Union. ; 8:2, s. 4499-4559
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Tidskriftsartikel (refereegranskat)abstract
- The Atmospheric Chemistry Experiment (ACE) mission was launched in August 2003 to sound the atmosphere by solar occultation. Water vapour (H2O), one of the most important molecules for climate and atmospheric chemistry, is one of the key species provided by the two principal instruments, the infrared Fourier Transform Spectrometer (ACE-FTS) and the MAESTRO UV-Visible spectrometer (ACE-MAESTRO). The first instrument performs measurements on several lines in the 1362–2137 cm−1 range, from which vertically resolved H2O concentration profiles are retrieved, from 7 to 90 km altitude. ACE-MAESTRO measures profiles using the water absorption band in the near infrared part of the spectrum at 926.0–969.7 nm. This paper presents a comprehensive validation of the ACE-FTS profiles. We have compared the H2O volume mixing ratio profiles with space-borne (SAGE II, HALOE, POAM III, MIPAS, SMR) observations and measurements from balloon-borne frostpoint hygrometers and a ground based lidar. We show that the ACE-FTS measurements provide H2O profiles with small retrieval uncertainties in the stratosphere (better than 5% from 15 to 70 km, gradually increasing above). The situation is unclear in the upper troposphere, due mainly to the high variability of the water vapour volume mixing ratio in this region. A new water vapour data product from the ACE-MAESTRO (Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation) is also presented and initial comparisons with ACE-FTS are discussed.
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| 7. |
- Willer, Cristen J., et al.
(författare)
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Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
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| 8. |
- Cullinane, CA, et al.
(författare)
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Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers
- 2005
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 117:6, s. 988-991
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Tidskriftsartikel (refereegranskat)abstract
- Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.
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| 9. |
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| 10. |
- Fang, Hsin-Yu, et al.
(författare)
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Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 114:4, s. 844-859
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Tidskriftsartikel (refereegranskat)abstract
- Ischemia exists in many diseased tissues, including arthritic joints, atherosclerotic plaques, and malignant tumors. Macrophages accumulate in these sites and up-regulate hypoxia-inducible transcription factors (HIFs) 1 and 2 in response to the hypoxia present. Here we show that the gene expression profile in primary human and murine macrophages changes markedly when they are exposed to hypoxia for 18 hours. For example, they were seen to up-regulate the cell surface receptors, CXCR4 and GLUT1, and the potent, tumor-promoting cytokines, vascular endothelial growth factor A, interleukin (IL)-1 beta and IL-8, adrenomedullin, CXCR4, and angiopoietin-2. Hypoxia also stimulated their expression and/or phosphorylation of various proteins in the nuclear factor-kappa B (NF-kappa B) signaling pathway. We then used both genetic and pharmacologic methods to manipulate the levels of HIFs-1 alpha and 2 alpha or NF-kappa B in primary macrophages to elucidate their role in the hypoxic induction of many of these key genes. These studies showed that both HIF-1 and -2, but not NF-kappa B, are important transcriptional effectors regulating the responses of macrophages to such a period of hypoxia. Further studies using experimental mouse models are now warranted to investigate the role of such macrophage responses in the progression of various diseased tissues, such as malignant tumors. (Blood. 2009; 114: 844-859)
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