| 1. |
- Hesselson, Stephanie E, et al.
(författare)
-
Genetic variation in the proximal promoter of ABC and SLC superfamilies : liver and kidney specific expression and promoter activity predict variation
- 2009
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:9, s. e6942-
-
Tidskriftsartikel (refereegranskat)abstract
- Membrane transporters play crucial roles in the cellular uptake and efflux of an array of small molecules including nutrients, environmental toxins, and many clinically used drugs. We hypothesized that common genetic variation in the proximal promoter regions of transporter genes contribute to observed variation in drug response. A total of 579 polymorphisms were identified in the proximal promoters (-250 to +50 bp) and flanking 5' sequence of 107 transporters in the ATP Binding Cassette (ABC) and Solute Carrier (SLC) superfamilies in 272 DNA samples from ethnically diverse populations. Many transporter promoters contained multiple common polymorphisms. Using a sliding window analysis, we observed that, on average, nucleotide diversity (pi) was lowest at approximately 300 bp upstream of the transcription start site, suggesting that this region may harbor important functional elements. The proximal promoters of transporters that were highly expressed in the liver had greater nucleotide diversity than those that were highly expressed in the kidney consistent with greater negative selective pressure on the promoters of kidney transporters. Twenty-one promoters were evaluated for activity using reporter assays. Greater nucleotide diversity was observed in promoters with strong activity compared to promoters with weak activity, suggesting that weak promoters are under more negative selective pressure than promoters with high activity. Collectively, these results suggest that the proximal promoter region of membrane transporters is rich in variation and that variants in these regions may play a role in interindividual variation in drug disposition and response.
|
|
| 2. |
- Mlynczak, Martin G., et al.
(författare)
-
Energy transport in the thermosphere during the solar storms of April 2002
- 2005
-
Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 110:A12
-
Tidskriftsartikel (refereegranskat)abstract
- The dramatic solar storm events of April 2002 deposited a large amount of energy into the Earth's upper atmosphere, substantially altering the thermal structure, the chemical composition, the dynamics, and the radiative environment. We examine the flow of energy within the thermosphere during this storm period from the perspective of infrared radiation transport and heat conduction. Observations from the SABER instrument on the TIMED satellite are coupled with computations based on the ASPEN thermospheric general circulation model to assess the energy flow. The dominant radiative response is associated with dramatically enhanced infrared emission from nitric oxide at 5.3 μm from which a total of ∼7.7 × 1023 ergs of energy are radiated during the storm. Energy loss rates due to NO emission exceed 2200 Kelvin per day. In contrast, energy loss from carbon dioxide emission at 15 μm is only ∼2.3% that of nitric oxide. Atomic oxygen emission at 63 μm is essentially constant during the storm. Energy loss from molecular heat conduction may be as large as 3.8% of the NO emission. These results confirm the “natural thermostat” effect of nitric oxide emission as the primary mechanism by which storm energy is lost from the thermosphere below 210 km.
|
|
| 3. |
- Mlynczak, Martin G., et al.
(författare)
-
Observations of infrared radiative cooling in the thermosphere on daily to multiyear timescales from the TIMED/SABER instrument
- 2010
-
Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 115:A3
-
Tidskriftsartikel (refereegranskat)abstract
- We present observations of the infrared radiative cooling by carbon dioxide (CO2) and nitric oxide (NO) in Earth's thermosphere. These data have been taken over a period of 7 years by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the NASA Thermosphere-Ionosphere-Mesosphere Energetics and Dynamics (TIMED) satellite and are the dominant radiative cooling mechanisms for the thermosphere. From the SABER observations we derive vertical profiles of radiative cooling rates (W m−3), radiative fluxes (W m−2), and radiated power (W). In the period from January 2002 through January 2009, we observe a large decrease in the cooling rates, fluxes, and power consistent with the declining phase of solar cycle 23. The power radiated by NO during 2008 when the Sun exhibited few sunspots was nearly one order of magnitude smaller than the peak power observed shortly after the mission began. Substantial short-term variability in the infrared emissions is also observed throughout the entire mission duration. Radiative cooling rates and radiative fluxes from NO exhibit fundamentally different latitude dependence than do those from CO2, with the NO fluxes and cooling rates being largest at high latitudes and polar regions. The cooling rates are shown to be derived relatively independent of the collisional and radiative processes that drive the departure from local thermodynamic equilibrium (LTE) in the CO2 15 μm and the NO 5.3 μm vibration-rotation bands. The observed NO and CO2 cooling rates have been compiled into a separate data set and represent a climate data record that is available for use in assessments of radiative cooling in upper atmosphere general circulation models.
|
|
| 4. |
- Mlynczak, Marty, et al.
(författare)
-
The natural thermostat of nitric oxide emission at 5.3 μm in the thermosphere observed during the solar storms of April 2002
- 2003
-
Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 30:21
-
Tidskriftsartikel (refereegranskat)abstract
- The Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) experiment on the Thermosphere-Ionosphere Mesosphere Energetics and Dynamics (TIMED) satellite observed the infrared radiative response of the thermosphere to the solar storm events of April 2002. Large radiance enhancements were observed at 5.3 μm, which are due to emission from the vibration-rotation bands of nitric oxide (NO). The emission by NO is indicative of the conversion of solar energy to infrared radiation within the atmosphere and represents a "natural thermostat" by which heat and energy are efficiently lost from the thermosphere to space and to the lower atmosphere. We describe the SABER observations at 5.3 μm and their interpretation in terms of energy loss. The infrared enhancements remain only for a few days, indicating that such perturbations to the thermospheric state, while dramatic, are short-lived. Copyright 2003 by the American Geophysical Union.
|
|
| 5. |
- Oji, Vinzenz, et al.
(författare)
-
Revised nomenclature and classification of inherited ichthyoses : Results of the First Ichthyosis Consensus Conference in Sorèze 2009
- 2010
-
Ingår i: The Journal of American Academy of Dermatology. - : Elsevier BV. - 0190-9622 .- 1097-6787. ; 63:4, s. 607-641
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inherited ichthyoses belong to a large, clinically and etiologically heterogeneous group of mendelian disorders of cornification, typically involving the entire integument. Over the recent years, much progress has been made defining their molecular causes. However, there is no internationally accepted classification and terminology. OBJECTIVE: We sought to establish a consensus for the nomenclature and classification of inherited ichthyoses. METHODS: The classification project started at the First World Conference on Ichthyosis in 2007. A large international network of expert clinicians, skin pathologists, and geneticists entertained an interactive dialogue over 2 years, eventually leading to the First Ichthyosis Consensus Conference held in Sorèze, France, on January 23 and 24, 2009, where subcommittees on different issues proposed terminology that was debated until consensus was reached. RESULTS: It was agreed that currently the nosology should remain clinically based. "Syndromic" versus "nonsyndromic" forms provide a useful major subdivision. Several clinical terms and controversial disease names have been redefined: eg, the group caused by keratin mutations is referred to by the umbrella term, "keratinopathic ichthyosis"-under which are included epidermolytic ichthyosis, superficial epidermolytic ichthyosis, and ichthyosis Curth-Macklin. "Autosomal recessive congenital ichthyosis" is proposed as an umbrella term for the harlequin ichthyosis, lamellar ichthyosis, and the congenital ichthyosiform erythroderma group. LIMITATIONS: As more becomes known about these diseases in the future, modifications will be needed. CONCLUSION: We have achieved an international consensus for the classification of inherited ichthyosis that should be useful for all clinicians and can serve as reference point for future research.
|
|
| 6. |
- Torchia, Jonathon, et al.
(författare)
-
Molecular subgroups of atypical teratoid rhabdoid tumours in children : an integrated genomic and clinicopathological analysis
- 2015
-
Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 16:5, s. 569-582
-
Tidskriftsartikel (refereegranskat)abstract
- Background Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. Methods We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. Findings Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0.004) and superior 5-year overall survival (35%, 95% CI 13-57, and 20%, 6-34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7-61, and 9%, 0-21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2.02 (95% CI 1.04-3.85; p=0.038) and 3.98 (1.71-9.26; p=0.001). Integrated analyses of molecular subgroupings with clinical prognostic factors showed three distinct clinical risk groups of tumours with different therapeutic outcomes. Interpretation An integration of clinical risk factors and tumour molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumours.
|
|
| 7. |
- van der Wurff, Richard, et al.
(författare)
-
Economic Growth and Advertising Expenditures in Different Media in Different Countries
- 2008
-
Ingår i: Journal of Media Economics. - : Informa UK Limited. - 0899-7764 .- 1532-7736. ; 21:1, s. 28-52
-
Tidskriftsartikel (refereegranskat)abstract
- Newspaper advertising expenditures depend more strongly on economic development than advertising spent in other media. Gross domestic product (GDP), therefore, predicts ad spending better in countries where newspapers are an important advertising medium. GDP also predicts ad spending better in countries where a larger proportion of GDP is spent on advertising. Intermedia competition, on the other hand, has little impact. In conclusion, the authors propose to distinguish three advertising cultures where ad spending follows economic development in different ways.
|
|
