| 1. |
- Berntsen, Peter, 1974, et al.
(författare)
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Biomechanical effects of environmental and engineered particles on human airway smooth muscle cells
- 2010
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 7:Suppl 3
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Tidskriftsartikel (refereegranskat)abstract
- The past decade has seen significant increases in combustion-generated ambient particles, which contain a nanosized fraction (less than 100 nm), and even greater increases have occurred in engineered nanoparticles (NPs) propelled by the booming nanotechnology industry. Although inhalation of these particulates has become a public health concern, human health effects and mechanisms of action for NPs are not well understood. Focusing on the human airway smooth muscle cell, here we show that the cellular mechanical function is altered by particulate exposure in a manner that is dependent upon particle material, size and dose. We used Alamar Blue assay to measure cell viability and optical magnetic twisting cytometry to measure cell stiffness and agonist-induced contractility. The eight particle species fell into four categories, based on their respective effect on cell viability and on mechanical function. Cell viability was impaired and cell contractility was decreased by (i) zinc oxide (40-100 nm and less than 44 mu m) and copper(II) oxide (less than 50 nm); cell contractility was decreased by (ii) fluorescent polystyrene spheres (40 nm), increased by (iii) welding fumes and unchanged by (iv) diesel exhaust particles, titanium dioxide (25 nm) and copper(II) oxide (less than 5 mu m), although in none of these cases was cell viability impaired. Treatment with hydrogen peroxide up to 500 mu M did not alter viability or cell mechanics, suggesting that the particle effects are unlikely to be mediated by particle-generated reactive oxygen species. Our results highlight the susceptibility of cellular mechanical function to particulate exposures and suggest that direct exposure of the airway smooth muscle cells to particulates may initiate or aggravate respiratory diseases.
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| 2. |
- Brain, D., et al.
(författare)
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A comparison of global models for the solar wind interaction with Mars
- 2010
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Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 206:1, s. 139-151
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Tidskriftsartikel (refereegranskat)abstract
- We present initial results from the first community-wide effort to compare global plasma interaction model results for Mars. Seven modeling groups participated in this activity, using MHD, multi-fluid, and hybrid assumptions in their simulations. Moderate solar wind and solar EUV conditions were chosen, and the conditions were implemented in the models and run to steady state. Model output was compared in three ways to determine how pressure was partitioned and conserved in each model, the location and asymmetry of plasma boundaries and pathways for planetary ion escape, and the total escape flux of planetary oxygen ions. The two participating MHD models provided similar results, while the five sets of multi-fluid and hybrid results were different in many ways. All hybrid results, however, showed two main channels for oxygen ion escape (a pickup ion 'plume' in the hemisphere toward which the solar wind convection electric field is directed, and a channel in the opposite hemisphere of the central magnetotail), while the MHD models showed one (a roughly symmetric channel in the central magnetotail). Most models showed a transition from an upstream region dominated by plasma dynamic pressure to a magnetosheath region dominated by thermal pressure to a low altitude region dominated by magnetic pressure. However, calculated escape rates for a single ion species varied by roughly an order of magnitude for similar input conditions, suggesting that the uncertainties in both the current and integrated escape over martian history as determined by models are large. These uncertainties are in addition to those associated with the evolution of the Sun, the martian dynamo, and the early atmosphere, highlighting the challenges we face in constructing Mars' past using models.
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| 3. |
- Bonnefoi, H., et al.
(författare)
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Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 25:6, s. 1128-1136
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Tidskriftsartikel (refereegranskat)abstract
- Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR], DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1). pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis.
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| 4. |
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| 5. |
- Dieval, Catherine, et al.
(författare)
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A case study of proton precipitation at Mars : Mars Express observations and hybrid simulations
- 2012
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 117
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Tidskriftsartikel (refereegranskat)abstract
- Using the data from the Analyzer of Space Plasma and Energetic Atoms (ASPERA-3) experiment on board Mars Express and hybrid simulations, we have investigated the entry of protons into the Martian induced magnetosphere. We discuss one orbit on the dayside with observations of significant proton fluxes at altitudes down to 260 km on 27 February 2004. The protons observed below the induced magnetosphere boundary at an altitude of less than 700 km have energies of a few keV, travel downward, and precipitate onto the atmosphere. The measured energy flux and particle flux are 108–109 eV cm−2 s−1 and 105–106 H+ cm−2 s−1, respectively. The proton precipitation occurs because the Martian magnetosheath is small with respect to the heated proton gyroradius in the subsolar region. The data suggest that the precipitation is not permanent but may occur when there are transient increases in the magnetosheath proton temperature. The higher-energy protons penetrate deeper because of their larger gyroradii. The proton entry into the induced magnetosphere is simulated using a hybrid code. A simulation using a fast solar wind as input can reproduce the high energies of the observed precipitating protons. The model shows that the precipitating protons originate from both the solar wind and the planetary exosphere. The precipitation extends over a few thousand kilometers along the orbit of the spacecraft. The proton precipitation does not necessarily correlate with the crustal magnetic anomalies.
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| 6. |
- Edberg, Niklas J. T., et al.
(författare)
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Magnetosonic Mach number effect of the position of the bow shock at Mars in comparison to Venus
- 2010
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 115, s. A07203-
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Tidskriftsartikel (refereegranskat)abstract
- We study the effect of the magnetosonic Mach number on the position of the bow shock (BS) at Mars. The magnetosonic Mach number is calculated from solar wind data obtained by the ACE satellite upstream of Earth and extrapolated to Mars during two intervals, starting in 2005 and 2007, when Mars and Earth were close to opposition. An increased Mach number is observed to cause the Martian BS to move to lower altitudes and the variation in the terminator altitude is proportional to the Mach number change. When the Mach number is lowered, the BS flares more. We also compare our results to previous studies at Venus. The variation in BS altitude with magnetosonic Mach number is found to be very similar to the variation of the Venusian BS, which has previously been shown to decrease linearly in altitude with increasing Mach number.
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| 9. |
- Grondin, Yohann, et al.
(författare)
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Pulmonary delivery of d-methionine is associated with an increase in ALCAR and glutathione in cochlear fluids.
- 2013
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Ingår i: Hearing Research. - : Elsevier BV. - 0378-5955 .- 1878-5891. ; 298, s. 93-103
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Tidskriftsartikel (refereegranskat)abstract
- In animals, hearing loss resulting from cochlear mechanosensory cell damage can be mitigated by antioxidants such as d-methionine (d-met) and acetyl-l-carnitine (ALCAR). The systemic routes of administration of these compounds, that must of necessity transit trough the cochlear fluids, may affect the antioxidant levels in the cochlea and the resulting oto-protective effect. In this study, we analyzed the pharmacokinetics of [C]d-met in the cochlea and four other tissues after intratracheal (IT), intranasal (IN), and oral by gavage (OG) administration and compared it to intravenous administration (IV). We then analyzed the effect of these four routes on the antioxidant content of the cochlear fluids after d-met or ALCAR administration, by liquid chromatography/mass spectrometry. Our results showed that the concentration of methionine and ALCAR in cochlear fluids significantly increased after their respective systemic administration. Interestingly, d-met administration also contributed to an increase of ALCAR. Our results also showed that the delivery routes differently affected the bioavailability of administered [C]d-met as well as the concentrations of methionine, ALCAR and the ratio of oxidized to reduced glutathione. Overall, pulmonary delivery via IT administration achieved high concentrations of methionine, ALCAR, and oxidative-related metabolites in cochlear fluids, in some cases surpassing IV administration, while IN route appeared to be the least efficacious. To our knowledge, this is the first report of the direct measurements of antioxidant levels in cochlear fluids after their systemic administration. This report also demonstrates the validity of the pulmonary administration of antioxidants and highlights the different contributions of d-met and ALCAR allowing to further investigate their impact on oxidative stress in the cochlear microenvironment.
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| 10. |
- Opgenoorth, Hermann J., et al.
(författare)
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Day-side ionospheric conductivities at Mars
- 2010
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Ingår i: Planetary and Space Science. - : Elsevier BV. - 0032-0633 .- 1873-5088. ; 58:10, s. 1139-1151
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Tidskriftsartikel (refereegranskat)abstract
- We present estimates of the day-side ionospheric conductivities at Mars based on magnetic field measurements by Mars Global Surveyor (MGS) at altitudes down to similar to 100 km during aerobraking orbits early in the mission. At Mars, the so-called ionospheric dynamo region, where plasma/neutral collisions permit electric currents perpendicular to the magnetic field, lies between 100 and 250 km altitude. We find that the ionosphere is highly conductive in this region, as expected, with peak Pedersen and Hall conductivities of 0.1-1.5 S/m depending on the solar illumination and induced magnetospheric conditions. Furthermore, we find a consistent double peak pattern in the altitude profile of the day-side Pedersen conductivity, similar to that on Titan found by Rosenqvist et al. (2009). A high altitude peak, located between 180 and 200 km, is equivalent to the terrestrial peak in the lower F-layer. A second and typically much stronger layer of Pedersen conductivity is observed between 120 and 130 km, which is below the Hall conductivity peak at about 130-140 km. In this altitude region, MGS finds a sharp decrease in induced magnetic field strength at the inner magnetospheric boundary, while the day-side electron density is known to remain high as far down as 100 km. We find that such Titan-like behaviour of the Pedersen conductivity is only observed under regions of strongly draped magnetospheric field-lines, and negligible crustal magnetic anomalies below the spacecraft. Above regions of strong crustal magnetic anomalies, the Pedersen conductivity profile becomes more Earth-like with one strong Pedersen peak above the Hall conductivity peak. Here, both conductivities are 1-2 orders of magnitude smaller than the above only weakly magnetised crustal regions, depending on the strength of the crustal anomaly field at ionospheric altitudes. This nature of the Pedersen conductivity together with the structured distribution of crustal anomalies all over the planet should give rise to strong conductivity gradients around such anomalies. Day-side ionospheric conductivities on Mars (in regions away from the crustal magnetic anomalies) and Titan seem to behave in a very similar manner when horizontally draped magnetic field-lines partially magnetise a sunlit ionosphere. Therefore, it appears that a similar double peak structure of strong Pedersen conductivity could be a more general feature of non-magnetised bodies with ionised upper atmospheres, and thus should be expected to occur also at other non-magnetised terrestrial planets like Venus or other planetary bodies within the host planet magnetospheres.
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