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- Coutard, B., et al.
(författare)
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The VIZIER project : Preparedness against pathogenic RNA viruses
- 2008
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Ingår i: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 78:1, s. 37-46
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Tidskriftsartikel (refereegranskat)abstract
- Life-threatening RNA viruses emerge regularly, and often in an unpredictable manner. Yet, the very few drugs available against known RNA viruses have sometimes required decades of research for development. Can we generate preparedness for outbreaks of the, as yet, unknown viruses? The VIZIER (VIral enZymes InvolvEd in Replication) (http://www.vizier-europe.org/) project has been set-up to develop the scientific foundations for countering this challenge to society. VIZIER studies the most conserved viral enzymes (that of the replication machinery, or replicases) that constitute attractive targets for drug-design. The aim of VIZIER is to determine as many replicase crystal structures as possible from a carefully selected list of viruses in order to comprehensively cover the diversity of the RNA virus universe, and generate critical knowledge that could be efficiently utilized to jump-start research on any emerging RNA virus. VIZIER is a multidisciplinary project involving (i) bioinformatics to define functional domains, (ii) viral genomics to increase the number of characterized viral genomes and prepare defined targets, (iii) proteomics to express, purify, and characterize targets, (iv) structural biology to solve their crystal structures, and (v) pre-lead discovery to propose active scaffolds of antiviral molecules.
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| 2. |
- Bensby, Thomas, et al.
(författare)
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OGLE-2009-BLG-076S: THE MOST METAL-POOR DWARF STAR IN THE GALACTIC BULGE
- 2009
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Ingår i: Astrophysical Journal. - 0004-637X. ; 699:2, s. 174-177
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Tidskriftsartikel (refereegranskat)abstract
- Measurements based on a large number of red giant stars suggest a broad metallicity distribution function (MDF) for the Galactic bulge, centered on [Fe/H] approximate to -0.1. However, recently, a new opportunity emerged to utilize temporary flux amplification (by factors of similar to 100 or more) of faint dwarf stars in the Bulge which are gravitationally lensed, making them observable with high-resolution spectrographs during a short observational window. Surprisingly, of the first six stars measured, five have [Fe/H] > +0.30, suggesting a highly skewed MDF, inconsistent with observations of giant stars. Here we present a detailed elemental abundance analysis of OGLE-2009-BLG-076S, based on a high-resolution spectrum obtained with the UVES spectrograph at the ESO Very Large Telescope. Our results indicate it is the most metal-poor dwarf star in the Bulge yet observed, with [Fe/H] = -0.76. Our results argue against a strong selection effect disfavoring metal-poor microlensed stars. It is possible that small number statistics is responsible for the giant/dwarf Bulge MDF discrepancy. Should this discrepancy survive when larger numbers of Bulge dwarf stars (soon to be available) are analyzed, it may require modification of our understanding of either Bulge formation models, or the behavior of metal-rich giant stars.
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| 6. |
- Wakelee, Heather A., et al.
(författare)
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Lung cancer incidence in never smokers
- 2007
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 25:5, s. 472-478
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Lung cancer is a leading cause of cancer death worldwide. Although smoking remains the predominant cause of lung cancer, lung cancer in never smokers is an increasingly prominent public health issue. However, data on this topic, particularly lung cancer incidence rates in never smokers, are limited. METHODS: We reviewed the existing literature on lung cancer incidence and mortality rates among never smokers and present new data regarding rates in never smokers from the following large, prospective cohorts: Nurses' Health Study; Health Professionals Follow-Up Study; California Teachers Study; Multiethnic Cohort Study; Swedish Lung Cancer Register in the Uppsala/Orebro region; and First National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study. RESULTS: Truncated age-adjusted incidence rates of lung cancer among never smokers age 40 to 79 years in these six cohorts ranged from 14.4 to 20.8 per 100,000 person-years in women and 4.8 to 13.7 per 100,000 person-years in men, supporting earlier observations that women are more likely than men to have non-smoking-associated lung cancer. The distinct biology of lung cancer in never smokers is apparent in differential responses to epidermal growth factor receptor inhibitors and an increased prevalence of adenocarcinoma histology in never smokers. CONCLUSION: Lung cancer in never smokers is an important public health issue, and further exploration of its incidence patterns, etiology, and biology is needed.
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| 7. |
- Crowley, S. D., et al.
(författare)
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Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis
- 2009
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Ingår i: J Clin Invest. - 1558-8238 .- 1558-8238 .- 0021-9738. ; 119:4, s. 943-53
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Tidskriftsartikel (refereegranskat)abstract
- Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT1) receptors in glomerular inflammation associated with autoimmune disease, we generated MRL-Faslpr/lpr (lpr) mice lacking the major murine type 1 angiotensin receptor (AT1A); lpr mice develop a generalized autoimmune disease with glomerulonephritis that resembles SLE. Surprisingly, AT1A deficiency was not protective against disease but instead substantially accelerated mortality, proteinuria, and kidney pathology. Increased disease severity was not a direct effect of immune cells, since transplantation of AT1A-deficient bone marrow did not affect survival. Moreover, autoimmune injury in extrarenal tissues, including skin, heart, and joints, was unaffected by AT1A deficiency. In murine systems, there is a second type 1 angiotensin receptor isoform, AT1B, and its expression is especially prominent in the renal glomerulus within podocytes. Further, expression of renin was enhanced in kidneys of AT1A-deficient lpr mice, and they showed evidence of exaggerated AT1B receptor activation, including substantially increased podocyte injury and expression of inflammatory mediators. Administration of losartan, which blocks all type 1 angiotensin receptors, reduced markers of kidney disease, including proteinuria, glomerular pathology, and cytokine mRNA expression. Since AT1A-deficient lpr mice had low blood pressure, these findings suggest that activation of type 1 angiotensin receptors in the glomerulus is sufficient to accelerate renal injury and inflammation in the absence of hypertension.
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| 8. |
- McKibben, Jodi B. A., et al.
(författare)
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Epidemiology of burn injuries II : Psychiatric and behavioral perspectives
- 2009
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Ingår i: International Review of Psychiatry. - : Informa UK Limited. - 0954-0261 .- 1369-1627. ; 21:6, s. 512-521
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Tidskriftsartikel (refereegranskat)abstract
- Modern technological advances have decreased the incidence and severity of burn injuries, and medical care improvements of burn injuries have significantly increased survival rates, particularly in developed countries. Still, fire-related burn injuries are responsible for 300,000 deaths and 10 million disability-adjusted life years lost annually worldwide. The extent to which psychiatric and behavioural factors contribute to the incidence and outcomes of these tragedies has not been systematically documented, and the available data is often insufficient to reach definitive conclusions. Accordingly, this article reviews the evidence of psychiatric and behavioural risk factors and prevention opportunities for burn injuries worldwide. Psychiatric prevalence rates and risk factors for burn injuries, prevalence and risks associated with 'intentional' burn injuries (self-immolation, assault, and child maltreatment), and prevention activities targeting the general population and those with known psychiatric and behavioural risk factors are discussed. These issues are substantially interwoven with many co-occurring risk factors. While success in teasing apart the roles and contributions of these factors rests upon improving the methodology employed in future research, the nature of this entanglement increases the likelihood that successful interventions in one problem area will reap benefits in others.
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