| 1. |
- Hillier, Ladeana W, et al.
(författare)
-
Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
-
Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
|
|
| 2. |
- Ashton, Nicholas J., et al.
(författare)
-
A multicentre validation study of the diagnostic value of plasma neurofilament light
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
|
|
| 3. |
- Bridel, Claire, et al.
(författare)
-
Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
-
Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
-
Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
|
|
| 4. |
- Gupta, Anil, et al.
(författare)
-
Postoperative analgesia after radical retropubic prostatectomy : a double-blind comparison between low thoracic epidural and patient-controlled intravenous analgesia
- 2006
-
Ingår i: Anesthesiology. - : Wolters Kluwer. - 0003-3022 .- 1528-1175. ; 105:4, s. 784-793
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Postoperative pain after radical retropubic prostatectomy can be severe unless adequately treated. Low thoracic epidural analgesia and patient-controlled intravenous analgesia were compared in this double-blind, randomized study.METHODS: Sixty patients were randomly assigned to receive either low thoracic epidural analgesia (group E) or patient-controlled intravenous analgesia (group P) for postoperative pain relief. All patients had general anesthesia combined with thoracic epidural analgesia during the operation. Postoperatively, patients in group E received an infusion of 1 mg/ml ropivacaine, 2 microg/ml fentanyl, and 2 microg/ml adrenaline, 10 ml/h during 48 h epidurally, and a placebo patient-controlled intravenous analgesia pump intravenously. Patients in group P received a patient-controlled intravenous analgesia pump with morphine intravenously and 10 ml/h placebo epidurally. Pain, the primary outcome variable, was measured using the numeric rating scale at rest (incision pain and "deep" visceral pain) and on coughing. Secondary outcome variables included gastrointestinal function, respiratory function, mobilization, and full recovery. Health-related quality of life was measured using the Short Form-36 questionnaire, and plasma concentration of fentanyl was measured in five patients to exclude a systemic effect of fentanyl.RESULTS: Incisional pain and pain on coughing were lower in group E compared with group P at 2-24 h, as was deep pain between 3 and 24 h postoperatively (P < 0.05). Maximum expiratory pressure was greater in group E at 4 and 24 h (P < 0.05) compared with group P. No difference in time to home discharge was found between the groups. The mean plasma fentanyl concentration varied from 0.2 to 0.3 ng/ml during 0-48 h postoperatively. At 1 month, the scores on emotional role, physical functioning, and general health of the Short Form-36 were higher in group E compared with group P. However, no group x time interaction was found in the Short Form-36.CONCLUSIONS: The authors found evidence for better pain relief and improved expiratory muscle function in patients receiving low thoracic epidural analgesia compared with patient-controlled analgesia for radical retropubic prostatectomy. Low thoracic epidural analgesia can be recommended as a good method for postoperative analgesia after abdominal surgery.
|
|
| 5. |
- Hibar, Derrek P., et al.
(författare)
-
Novel genetic loci associated with hippocampal volume
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
|
|
| 6. |
- Jakobson Mo, Susanna, et al.
(författare)
-
Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT – a clinical comparison
- 2018
-
Ingår i: EJNMMI Research. - : Springer. - 2191-219X. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Dopamine transporter (DAT) imaging may be of diagnostic value in patients with clinically suspected parkinsonian disease. The purpose of this study was to compare the diagnostic performance of DAT imaging with positron emission computed tomography (PET), using the recently developed, highly DAT-selective radiopharmaceutical [18F]FE-PE2I (FE-PE2I), to the commercially available and frequently used method with [123I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) in early-stage idiopathic parkinsonian syndrome (PS).Methods: Twenty-two patients with a clinical de novo diagnosis of PS and 28 healthy controls (HC) participating in an on-going clinical trial of FE-PE2I were analyzed in this study. Within the trial protocol, participants are clinically reassessed 2 years after inclusion. A commercially available software was used for automatic calculation of FP-CIT-specific uptake ratio (SUR). MRI-based volumes of interest combined with threshold PET segmentation were used for FE-PE2I binding potential relative to non-displaceable binding (BPND) quantification and specific uptake value ratios (SUVR).Results: PET with FE-PE2I revealed significant differences between patients with a clinical de novo diagnosis of PS and healthy controls in striatal DAT availability (p < 0.001), with excellent accuracy of predicting dopaminergic deficit in early-stage PS. The effect sizes were calculated for FE-PE2I BPND (Glass’s Δ = 2.95), FE-PE2I SUVR (Glass’s Δ = 2.57), and FP-CIT SUR (Glass’s Δ = 2.29). The intraclass correlation (ICC) between FE-PE2I BPND FP-CIT SUR was high in the caudate (ICC = 0.923), putamen (ICC = 0.922), and striatum (ICC = 0.946), p < 0.001. Five of the 22 patients displayed preserved striatal DAT availability in the striatum with both methods. At follow-up, a non-PS clinical diagnosis was confirmed in three of these, while one was clinically diagnosed with corticobasal syndrome. In these patients, FE-PE2I binding was also normal in the substantia nigra (SN), while significantly reduced in the remaining patients. FE-PE2I measurement of the mean DAT availability in the putamen was strongly correlated with BPND in the SN (R = 0.816, p < 0.001). Olfaction and mean putamen DAT availability was correlated using both FE-PE2I BPND and FP-CIT SUR (R ≥ 0.616, p < 0.001).Conclusion: DAT imaging with FE-PE2I PET yields excellent basic diagnostic differentiation in early-stage PS, at least as good as FP-CIT SPECT.
|
|
| 7. |
- Lizana, Helena, et al.
(författare)
-
Whole-Body Biodistribution and Dosimetry of the Dopamine Transporter Radioligand 18F-FE-PE2I in Human Subjects
- 2018
-
Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 59:8, s. 1275-1280
-
Tidskriftsartikel (refereegranskat)abstract
- F-18-(E)-N-(3-iodoprop-2-enyl)-2 beta-carbofluoroethoxy-3 beta-(4'-methylphenyl) nortropane (F-18-FE-PE2I) was recently developed and has shown adequate affinity and high selectivity for the dopamine transporter (DAT). Previous studies have shown promising results for F-18-FE-PE2I as a suitable radioligand for DAT imaging. In this study, we investigated the whole-body biodistribution and dosimetry of F-18-FE-PE2I in healthy volunteers to support its utility as a suitable PET imaging agent for the DAT. Methods: Five healthy volunteers were given a mean activity of 2.5 MBq/kg, and 3 PET scans, head to thigh, were performed immediately after injection followed by 4 whole-body PET/CT scans between 0.5 and 6 h after injection. Blood samples were drawn in connection with the whole-body scans, and all urine was collected until 6 h after injection. Volumes of interest were delineated around 17 organs on all images, and the areas under the time-activity curves were calculated to obtain the total number of decays in the organs. The absorbed doses to organs and the effective dose were calculated using the software IDAC. Results: The highest activity concentration was observed in the liver (0.9%-1.2% injected activity/100 g) up to 30 min after injection. At later time points, the highest concentration was seen in the gallbladder (1.1%-0.1% injected activity/100 g). The activity excreted with urine ranged between 23% and 34%, with a mean of 28%. The urinary bladder received the highest absorbed dose (119 mu Gy/MBq), followed by the liver (46 mu Gy/MBq). The effective dose was 23 mu Sv/MBq (range, 19-28 mu Sv/MBq), resulting in an effective dose of 4.6 mSv for an administered activity of 200 MBq. Conclusion: The effective dose is within the same order of magnitude as other commonly used PET imaging agents as well as DAT agents. The reasonable effective dose, together with the previously reported favorable characteristics for DAT imaging and quantification, indicates that F-18-FE-PE2I is a suitable radioligand for DAT imaging.
|
|
| 8. |
- Novakova, Lenka, 1984, et al.
(författare)
-
Cerebrospinal fluid sulfatide isoforms lack diagnostic utility in separating progressive from relapsing-remitting multiple sclerosis.
- 2023
-
Ingår i: Multiple sclerosis and related disorders. - 2211-0356. ; 74
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system. The glycosphingolipid sulfatide, a lipid particularly enriched in the myelin sheath, has been shown to be involved the maintenance of this specific membrane structure. Sulfatide in cerebrospinal fluid (CSF) may reflect demyelination, a dominating feature of MS. We investigated the diagnostic utility of CSF sulfatide isoform levels to separate different courses or phenotypes of MS disease.This was a mono-center, cross-sectional study of relapsing-remitting MS (RRMS) (n=45) and progressive MS (PMS) (n=42) patients (consisting of primary PMS (n=17) and secondary PMS (n=25)) and healthy controls (n=19). In total, 20 sulfatide isoforms were measured in CSF by liquid chromatography-mass spectrometry.CSF total sulfatide concentrations, as well as CSF sulfatide isoform distribution, did not differ across the study groups, and their levels were independent of disease course/phenotype, disease duration, time to conversion to secondary PMS, age, and disability in MS patients.CSF sulfatide isoforms lack diagnostic and prognostic utility as a biomarker for progressive MS.
|
|
| 9. |
- Novakova, Lenka, 1984, et al.
(författare)
-
Sulfatide isoform pattern in cerebrospinal fluid discriminates progressive MS from relapsing-remitting MS
- 2018
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042. ; 146:3, s. 322-332
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Several biomarkers including proteins and lipids have been reported in MS cerebrospinal fluid (CSF), reflecting different aspects of the pathophysiology particularly of relapsing-remitting MS (RRMS). Sulfatide, abundant in the myelin sheath and a proposed target for autoimmune attack in MS, has been reported altered in MS CSF. Here, we investigated the potential of CSF sulfatide and its isoforms as biomarkers in MS. A highly sensitive and quantitative mass spectrometry method was employed to determine levels of sulfatide isoforms in CSF from RRMS and progressive MS (PMS) patients, and healthy donors (HD). We demonstrate that levels of total CSF sulfatide and C24:1, C26:1, and C26:1-OH isoforms were significantly increased in PMS compared with RRMS patients and HD, while C23:0-OH was significantly decreased in CSF from PMS patients compared to the other two groups. Multivariate discriminant analysis showed that CSF sulfatide isoform pattern in PMS patients was distinct and non-overlapping with that of RRMS patients and HD. Sulfatide levels did not correlate with tested biomarkers or clinical parameters. The results suggest that CSF sulfatide isoform levels may be used to discriminate the phenotype ofMS and might play a role in the progression of the disease.
|
|
| 10. |
- Paulander, Jörgen, 1942, et al.
(författare)
-
Intra-oral pattern of tooth and periodontal bone loss between the age of 50 and 60 years. A longitudinal prospective study.
- 2004
-
Ingår i: Acta odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 62:4, s. 214-22
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In a 10-year prospective study we analyzed (i) the intra-oral pattern of and (ii) potential risk factors for tooth and periodontal bone loss in 50-year-old individuals. METHODS: A randomized subject sample of 50-year-old inhabitants in the County of Varmland, Sweden, was examined at baseline and after 10 years. Data from full-mouth clinical and radiographic examinations and questionnaire surveys of 309 (72%) of the individuals who were dentate at baseline were available for analysis. Non-parametric tests and binary logistic multiple regression models were used for statistical analysis of the data. RESULTS: 4.1% of the 7,101 teeth present at baseline, distributed among 39% of the subjects, were lost during the 10-year interval. The incidence of tooth loss was highest among mandibular molars (7.5%) and lowest among canines (1.8%). The relative risk (RR) for tooth loss for endodontically compromised teeth was 4.1 and for furcation-involved molars 2.4-6.5, depending on tooth position. Logistic regression analysis identified baseline alveolar bone level (ABL), endodontic conditions, CPITN score (Community Periodontal Index of Treatment Needs), tooth position, caries, and educational level as risk factors for tooth loss. The overall mean 10-year ABL change was -0.54 mm (S.E. 0.01). On a tooth level the ABL change varied between -0.35 mm (mandibular molars) and -0.79 mm (mandibular incisors). Smokers experienced a greater (20-131% depending on tooth type) mean bone loss than non-smokers. The logistic regression model revealed that tooth position, smoking, and probing pocket depth > or =4 mm were risk factors for bone loss of >1 mm. No pertinent differences were observed with respect to risk factors for ABL change in the subgroup of non-smokers compared to the results of the analysis based on the entire subject sample. CONCLUSION: Tooth loss was more common in the molar than in the anterior tooth regions, while periodontal bone loss had a random distribution in the dentition. The predominant risk factors identified with regard to further radiographic bone loss were "probing pocket depth > or =6 mm" and "smoking".
|
|
| 11. |
- Paulander, Jörgen, 1942, et al.
(författare)
-
Some characteristics of 50/55-year-old individuals with various experience of destructive periodontal disease: a cross-sectional study.
- 2004
-
Ingår i: Acta odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 62:4, s. 199-206
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the association between subject characteristics and degree of destructive periodontal disease in a randomly selected sample of 50/55-year-old individuals. METHODS: A randomized and geographically stratified (urban/rural districts) subject sample composed of dentate 50-year-old (n = 190) and 55-year-old individuals (n = 359) from the county of Varmland, Sweden were examined. Data were collected through full mouth clinical and radiographic examinations and by the use of questionnaires. Based on the cumulative distribution of the individuals with respect to mean probing attachment loss (PAL), subgroups of subjects with the lowest (L20%) and highest (H20%) experience of PAL were identified. Similar classifications were made for never-smokers and current smokers. Correlation analyses and forward stepwise logistic regression models were performed. RESULTS: The subgroup with the most extensive PAL loss (H20%) included a significantly higher proportion of (i) males (60 vs 33%), (ii) subjects with low educational level (65 vs 41%), (iii) smokers (49 vs 15%), and had (iv) less favorable lifestyle characteristics than the subgroup with minimal experience of PAL loss (L20%). The same pattern of differences was observed when the analysis was restricted to never-smokers, with the addition of a significantly lower proportion of subjects living in urban areas (40 vs 69%) in the H20% compared to the L20% subgroup. The stepwise logistic regression analysis revealed that number of teeth and smoking habits were significant factors in the identification of individuals in the L20% subgroup. For the H20% subgroup, number of teeth, gender, number of cigarettes/day and lifestyle index were significant explanatory variables. CONCLUSION: Number of remaining teeth and smoking habits were identified as the main discriminating factors for classification of subjects with regard to degree of destructive periodontal disease.
|
|
| 12. |
- Paulander, Jörgen, 1942, et al.
(författare)
-
Some risk factors for periodontal bone loss in 50-year-old individuals. A 10-year cohort study
- 2004
-
Ingår i: Journal Of Clinical Periodontology. ; 31:7, s. 489-96
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this 10-year prospective study of 50-year-old individuals was to analyze the incidence of periodontal bone loss and potential risk factors for periodontal bone loss. METHODS: The subject sample was generated from an epidemiological survey performed in 1988 of subjects living in the County of Varmland, Sweden. A randomized sample of 15% of the 50-year-old inhabitants in the county was drawn. At the 10-year follow-up in 1998, 320 (75%) of the 449 individuals examined at baseline were available for re-examination, out of which 4 had become edentulous. Full-mouth clinical and radiographic examinations and questionnaire surveys were performed in 1988 and 1998. Two hundred and ninety-five individuals (69%) had complete data for inclusion in the analysis of radiographic bone changes over 10 years. Non-parametric tests, correlations and stepwise multiple regression models were used for statistical analysis of the data. RESULTS: The mean alveolar bone level (ABL) in 1988 was 2.2 mm (0.05) and a further 0.4 mm (0.57) (p=0.000) was lost over the 10 years. Eight percent of the subject sample showed no loss, while 5% experienced a mean bone loss of >/=1 mm. Smoking was found to be the strongest individual risk predictor (RR=3.2; 95% CI 2.03-5.15). When including as smokers only those individuals who had continued with the habit during the entire 10-year follow-up period, the relative risk was slightly increased (3.6; 95% CI 2.32-5.57). Subjects who had quit smoking before the baseline examination did not demonstrate a significantly increased risk for disease progression (RR=1.3; 95% CI 0.57-2.96). Stepwise multiple regression analysis revealed that smoking, % approximal sites with probing pocket depth >/=4 mm, number of teeth and systemic disease were significant explanatory factors for 10-year ABL loss (R(2)=0.12). For never smokers, statistically significant predictors were number of teeth, mean ABL, % periodontally healthy approximal sites and educational level (R(2)=0.20). CONCLUSION: The inclusion of smokers in risk analysis for periodontal diseases may obstruct the possibility to detect other true risk factors and risk indicators.
|
|
| 13. |
- Satizabal, Claudia L., et al.
(författare)
-
Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
-
Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
|
|
| 14. |
- Velut, Stephane, et al.
(författare)
-
Influence of bioreactor scale and complex medium on probing control of glucose feeding in cultivations of recombinant strains of Escherichia coli
- 2007
-
Ingår i: Biotechnology and Bioengineering. - : Wiley. - 1097-0290 .- 0006-3592. ; 97:4, s. 816-824
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this work was to evaluate the performance of a feedback glucose control strategy (the probing strategy) in production relevant bioreactors with complex and mineral media. Experimental results from fedbatch cultivations with two recombinant Escherichia coli constructs expressing two different human therapeutic proteins were used to assess the performance and limitations of the glucose probing technique. Even though the performance of the probing strategy was affected by scale and complex media, this methodology rapidly identified a glucose feed protocol similar to an experimentally derived feed regime. This methodology may serve as a powerful tool for industrial process development and in optimization of glucose feed regimes when transferring process technology from one bioreactor system to another.
|
|
| 15. |
- Abdo, A. A., et al.
(författare)
-
A limit on the variation of the speed of light arising from quantum gravity effects
- 2009
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 462:7271, s. 331-334
-
Tidskriftsartikel (refereegranskat)abstract
- A cornerstone of Einstein’s special relativity is Lorentz invariance—the postulate that all observers measure exactly the same speed of light in vacuum, independent of photon-energy. While special relativity assumes that there is no fundamental length-scale associated with such invariance, there is a fundamental scale (the Planck scale, lPlanck~1.62×10-33cm or EPlanck = MPlanckc2~1.22×1019GeV), at which quantum effects are expected to strongly affect the nature of space–time. There is great interest in the (not yet validated) idea that Lorentz invariance might break near the Planck scale. A key test of such violation of Lorentz invariance is a possible variation of photon speed with energy. Even a tiny variation in photon speed, when accumulated over cosmological light-travel times, may be revealed by observing sharp features in γ-ray burst (GRB) light-curves. Here we report the detection of emission up to ~31GeV from the distant and short GRB090510. We find no evidence for the violation of Lorentz invariance, and place a lower limit of 1.2EPlanck on the scale of a linear energy dependence (or an inverse wavelength dependence), subject to reasonable assumptions about the emission (equivalently we have an upper limit of lPlanck/1.2 on the length scale of the effect). Our results disfavour quantum-gravity theories in which the quantum nature of space–time on a very small scale linearly alters the speed of light.
|
|
| 16. |
- Abdo, A. A., et al.
(författare)
-
A Population of Gamma-Ray Millisecond Pulsars Seen with the Fermi Large Area Telescope
- 2009
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5942, s. 848-852
-
Tidskriftsartikel (refereegranskat)abstract
- Pulsars are born with subsecond spin periods and slow by electromagnetic braking for several tens of millions of years, when detectable radiation ceases. A second life can occur for neutron stars in binary systems. They can acquire mass and angular momentum from their companions, to be spun up to millisecond periods and begin radiating again. We searched Fermi Large Area Telescope data for pulsations from all known millisecond pulsars (MSPs) outside of globular clusters, using rotation parameters from radio telescopes. Strong gamma-ray pulsations were detected for eight MSPs. The gamma-ray pulse profiles and spectral properties resemble those of young gamma-ray pulsars. The basic emission mechanism seems to be the same for MSPs and young pulsars, with the emission originating in regions far from the neutron star surface.
|
|
| 17. |
- Abdo, A. A., et al.
(författare)
-
BRIGHT ACTIVE GALACTIC NUCLEI SOURCE LIST FROM THE FIRST THREE MONTHS OF THE FERMI LARGE AREA TELESCOPE ALL-SKY SURVEY
- 2009
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 700:1, s. 597-622
-
Tidskriftsartikel (refereegranskat)abstract
- The first three months of sky-survey operation with the Large Area Telescope (LAT) onboard the Fermi Gamma-Ray Space Telescope reveal 132 bright sources at |b| > 10 degrees with test statistic greater than 100 ( corresponding to about 10 sigma). Two methods, based on the CGRaBS, CRATES, and BZCat catalogs, indicate high-confidence associations of 106 of these sources with known active galactic nuclei (AGNs). This sample is referred to as the LAT Bright AGN Sample (LBAS). It contains two radio galaxies, namely, Centaurus A and NGC 1275, and 104 blazars consisting of 58 flat spectrum radio quasars (FSRQs), 42 BL Lac objects, and 4 blazars with unknown classification. Four new blazars were discovered on the basis of the LAT detections. Remarkably, the LBAS includes 10 high-energy-peaked BL Lacs (HBLs), sources which were previously difficult to detect in the GeV range. Another 10 lower-confidence associations are found. Only 33 of the sources, plus two at |b| < 10 degrees, were previously detected with Energetic Gamma-Ray Experiment Telescope( EGRET), probably due to variability. The analysis of the gamma-ray properties of the LBAS sources reveals that the average GeV spectra of BL Lac objects are significantly harder than the spectra of FSRQs. No significant correlation between radio and peak gamma-ray fluxes is observed. Blazar log N-log S distributions and luminosity functions are constructed to investigate the evolution of the different blazar classes, with positive evolution indicated for FSRQs but none for BL Lacs. The contribution of LAT blazars to the total extragalactic gamma-ray intensity is estimated.
|
|
| 18. |
- Abdo, A. A., et al.
(författare)
-
Detection of High-Energy Gamma-Ray Emission from the Globular Cluster 47 Tucanae with Fermi
- 2009
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5942, s. 845-848
-
Tidskriftsartikel (refereegranskat)abstract
- We report the detection of gamma-ray emissions above 200 megaelectron volts at a significance level of 17 sigma from the globular cluster 47 Tucanae, using data obtained with the Large Area Telescope onboard the Fermi Gamma-ray Space Telescope. Globular clusters are expected to emit gamma rays because of the large populations of millisecond pulsars that they contain. The spectral shape of 47 Tucanae is consistent with gamma-ray emission from a population of millisecond pulsars. The observed gamma-ray luminosity implies an upper limit of 60 millisecond pulsars present in 47 Tucanae.
|
|
| 19. |
- Abdo, A. A., et al.
(författare)
-
DISCOVERY OF PULSATIONS FROM THE PULSAR J0205+6449 IN SNR 3C 58 WITH THE FERMI GAMMA-RAY SPACE TELESCOPE
- 2009
-
Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 0004-637X .- 1538-4357. ; 699:2, s. L102-L107
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of gamma-ray pulsations (>= 0.1 GeV) from the young radio and X-ray pulsar PSR J0205 + 6449 located in the Galactic supernova remnant 3C 58. Data in the gamma-ray band were acquired by the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope (formerly GLAST), while the radio rotational ephemeris used to fold gamma-rays was obtained using both the Green Bank Telescope and the Lovell telescope at Jodrell Bank. The light curve consists of two peaks separated by 0.49 +/- 0.01 +/- 0.01 cycles which are aligned with the X-ray peaks. The first gamma-ray peak trails the radio pulse by 0.08 +/- 0.01 +/- 0.01, while its amplitude decreases with increasing energy as for the other gamma-ray pulsars. Spectral analysis of the pulsed gamma-ray emission suggests a simple power law of index -2.1 +/- 0.1 +/- 0.2 with an exponential cutoff at 3.0(-0.7)(+1.1) +/- 0.4 GeV. The first uncertainty is statistical and the second is systematic. The integral gamma-ray photon flux above 0.1 GeV is (13.7 +/- 1.4 +/- 3.0) x 10(-8) cm(-2) s(-1), which implies for a distance of 3.2 kpc and assuming a broad fan-like beam a luminosity of 8.3 x 10(34) erg s(-1) and an efficiency eta of 0.3%. Finally, we report a 95% upper limit on the flux of 1.7 x 10(-8) cm(-2) s(-1) for off-pulse emission from the object.
|
|
| 20. |
- Abdo, A. A., et al.
(författare)
-
EARLY FERMI GAMMA-RAY SPACE TELESCOPE OBSERVATIONS OF THE QUASAR 3C 454.3
- 2009
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 699:1, s. 817-823
-
Tidskriftsartikel (refereegranskat)abstract
- This is the first report of Fermi Gamma-Ray Space Telescope observations of the quasar 3C 454.3, which has been undergoing pronounced long-term outbursts since 2000. The data from the Large Area Telescope, covering 2008 July 7-October 6, indicate strong, highly variable.-ray emission with an average flux of similar to 3 x 10 (6) photons cm(-2) s(-1), for energies > 100 MeV. The gamma-ray flux is variable, with strong, distinct, symmetrically shaped flares for which the flux increases by a factor of several on a timescale of about 3 days. This variability indicates a compact emission region, and the requirement that the source is optically thin to pair production implies relativistic beaming with Doppler factor delta > 8, consistent with the values inferred from Very Long Baseline Interferometry observations of superluminal expansion (delta similar to 25). The observed gamma-ray spectrum is not consistent with a simple power law, but instead steepens strongly above similar to 2 GeV, and is well described by a broken power law with photon indices of similar to 2.3 and similar to 3.5 below and above the break, respectively. This is the first direct observation of a break in the spectrum of a high-luminosity blazar above 100 MeV, and it is likely direct evidence for an intrinsic break in the energy distribution of the radiating particles. Alternatively, the spectral softening above 2 GeV could be due to gamma-ray absorption via photon-photon pair production on the soft X-ray photon field of the host active galactic nucleus, but such an interpretation would require the dissipation region to be located very close (less than or similar to 100 gravitational radii) to the black hole, which would be inconsistent with the X-ray spectrum of the source.
|
|
| 21. |
- Abdo, A. A., et al.
(författare)
-
FERMI/LARGE AREA TELESCOPE BRIGHT GAMMA-RAY SOURCE LIST
- 2009
-
Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 183:1, s. 46-66
-
Tidskriftsartikel (refereegranskat)abstract
- Following its launch in 2008 June, the Fermi Gamma-ray Space Telescope (Fermi) began a sky survey in August. The Large Area Telescope (LAT) on Fermi in three months produced a deeper and better resolved map of the gamma-ray sky than any previous space mission. We present here initial results for energies above 100 MeV for the 205 most significant (statistical significance greater than similar to 10 sigma) gamma-ray sources in these data. These are the best characterized and best localized point-like (i.e., spatially unresolved) gamma-ray sources in the early mission data.
|
|
| 22. |
- Abdo, A. A., et al.
(författare)
-
FERMI/LARGE AREA TELESCOPE DISCOVERY OF GAMMA-RAY EMISSION FROM A RELATIVISTIC JET IN THE NARROW-LINE QUASAR PMN J0948+0022
- 2009
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 699:2, s. 976-984
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery by the Large Area Telescope (LAT) onboard the Fermi Gamma-Ray Space Telescope of high-energy. gamma-ray emission from the peculiar quasar PMN J0948+0022 (z = 0.5846). The optical spectrum of this object exhibits rather narrow H beta (FWHM(H beta) similar to 1500 km s(-1)), weak forbidden lines, and is therefore classified as a narrow-line type I quasar. This class of objects is thought to have relatively small black hole mass and to accrete at a high Eddington ratio. The radio loudness and variability of the compact radio core indicate the presence of a relativistic jet. Quasi-simultaneous radio/optical/X-ray and gamma-ray observations are presented. Both radio and gamma-ray emissions (observed over five months) are strongly variable. The simultaneous optical and X-ray data from Swift show a blue continuum attributed to the accretion disk and a hard X-ray spectrum attributed to the jet. The resulting broadband spectral energy distribution (SED) and, in particular, the gamma-ray spectrum measured by Fermi are similar to those of more powerful Flat-Spectrum Radio Quasars (FSRQs). A comparison of the radio and gamma-ray characteristics of PMN J0948+0022 with the other blazars detected by LAT shows that this source has a relatively low radio and gamma-ray power with respect to other FSRQs. The physical parameters obtained from modeling the SED also fall at the low power end of the FSRQ parameter region discussed in Celotti & Ghisellini. We suggest that the similarity of the SED of PMN J0948+0022 to that of more massive and more powerful quasars can be understood in a scenario in which the SED properties depend on the Eddington ratio rather than on the absolute power.
|
|
| 23. |
- Abdo, A. A., et al.
(författare)
-
FERMI/LARGE AREA TELESCOPE DISCOVERY OF GAMMA-RAY EMISSION FROM THE FLAT-SPECTRUM RADIO QUASAR PKS 1454-354
- 2009
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 697:1, s. 934-941
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery by the Large Area Telescope (LAT) onboard the Fermi Gamma-Ray Space Telescope of high-energy gamma-ray (GeV) emission from the flat-spectrum radio quasar PKS 1454-354 (z = 1.424). On 2008 September 4, the source rose to a peak flux of (3.5 +/- 0.7) x 10(-6) ph cm(-2) s(-1) (E > 100 MeV) on a timescale of hours and then slowly dropped over the following 2 days. No significant spectral changes occurred during the flare. Fermi/LAT observations also showed that PKS 1454-354 is the most probable counterpart of the unidentified EGRET source 3EG J1500-3509. Multiwavelength measurements performed during the following days (7 September with Swift; 6-7 September with the ground-based optical telescope Automated Telescope for Optical Monitoring; 13 September with the Australia Telescope Compact Array) resulted in radio, optical, UV, and X-ray fluxes greater than archival data, confirming the activity of PKS 1454-354.
|
|
| 24. |
- Abdo, A. A., et al.
(författare)
-
FERMI LARGE AREA TELESCOPE GAMMA-RAY DETECTION OF THE RADIO GALAXY M87
- 2009
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 707:1, s. 55-60
-
Tidskriftsartikel (refereegranskat)abstract
- We report the Fermi Large Area Telescope (LAT) discovery of high-energy (MeV/GeV) gamma-ray emission positionally consistent with the center of the radio galaxy M87, at a source significance of over 10 sigma in 10 months of all-sky survey data. Following the detections of Cen A and Per A, this makes M87 the third radio galaxy seen with the LAT. The faint point-like gamma-ray source has a >100 MeV flux of 2.45 (+/-0.63) x 10(-8) photons cm(-2) s(-1) (photon index = 2.26 +/- 0.13) with no significant variability detected within the LAT observation. This flux is comparable with the previous EGRET upper limit (<2.18 x 10-8 photons cm(-2) s(-1), 2 sigma), thus there is no evidence for a significant MeV/GeV flare on decade timescales. Contemporaneous Chandra and Very Long Baseline Array data indicate low activity in the unresolved X-ray and radio core relative to previous observations, suggesting M87 is in a quiescent overall level over the first year of Fermi-LAT observations. The LAT gamma-ray spectrum is modeled as synchrotron self-Compton (SSC) emission from the electron population producing the radio-to-X-ray emission in the core. The resultant SSC spectrum extrapolates smoothly from the LAT band to the historical-minimum TeV emission. Alternative models for the core and possible contributions from the kiloparsec-scale jet in M87 are considered, and cannot be excluded.
|
|
| 25. |
- Abdo, A. A., et al.
(författare)
-
Fermi LAT Observation of Diffuse Gamma Rays Produced Through Interactions Between Local Interstellar Matter and High-energy Cosmic Rays
- 2009
-
Ingår i: Astrophysical Journal Supplement Series. - 0067-0049 .- 1538-4365. ; 703:2, s. 1249-1256
-
Tidskriftsartikel (refereegranskat)abstract
- Observations by the Large Area Telescope (LAT) on the Fermi mission of diffuse γ-rays in a mid-latitude region in the third quadrant (Galactic longitude l from 200° to 260° and latitude |b| from 22° to 60°) are reported. The region contains no known large molecular cloud and most of the atomic hydrogen is within 1 kpc of the solar system. The contributions of γ-ray point sources and inverse Compton scattering are estimated and subtracted. The residual γ-ray intensity exhibits a linear correlation with the atomic gas column density in energy from 100 MeV to 10 GeV. The measured integrated γ-ray emissivity is (1.63 ± 0.05) × 10-26 photons s-1sr-1 H-atom-1 and (0.66 ± 0.02) × 10-26 photons s-1sr-1 H-atom-1 above 100 MeV and above 300 MeV, respectively, with an additional systematic error of ~10%. The differential emissivity from 100 MeV to 10 GeV agrees with calculations based on cosmic ray spectra consistent with those directly measured, at the 10% level. The results obtained indicate that cosmic ray nuclei spectra within 1 kpc from the solar system in regions studied are close to the local interstellar spectra inferred from direct measurements at the Earth within ~10%.
|
|
