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  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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  • Haberle, R. M., et al. (author)
  • Preliminary interpretation of the REMS pressure data from the first 100 sols of the MSL mission
  • 2014
  • In: Journal of Geophysical Research - Planets. - : John Wiley & Sons. - 2169-9097 .- 2169-9100. ; 119:3, s. 440-453
  • Journal article (peer-reviewed)abstract
    • We provide a preliminary interpretation of the Rover Environmental Monitoring Station (REMS) pressure data from the first 100 Martian solar days (sols) of the Mars Science Laboratory mission. The pressure sensor is performing well and has revealed the existence of phenomena undetected by previous missions that include possible gravity waves excited by evening downslope flows, relatively dust-free convective vortices analogous in structure to dust devils, and signatures indicative of the circulation induced by Gale Crater and its central mound. Other more familiar phenomena are also present including the thermal tides, generated by daily insolation variations, and the CO2 cycle, driven by the condensation and sublimation of CO2 in the polar regions. The amplitude of the thermal tides is several times larger than those seen by other landers primarily because Curiosity is located where eastward and westward tidal modes constructively interfere and also because the crater circulation amplifies the tides to some extent. During the first 100 sols tidal amplitudes generally decline, which we attribute to the waning influence of the Kelvin wave. Toward the end of the 100 sol period, tidal amplitudes abruptly increased in response to a nearby regional dust storm that did not expand to global scales. Tidal phases changed abruptly during the onset of this storm suggesting a change in the interaction between eastward and westward modes. When compared to Viking Lander 2 data, the REMS daily average pressures show no evidence yet for the 1-20 Pa increase expected from the possible loss of CO 2 from the south polar residual cap. Key Points REMS pressure sensor is operating nominally New phenomena have been discovered Familiar phenomena have been detected ©2014. American Geophysical Union. All Rights Reserved.
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  • Harri, A.-M., et al. (author)
  • Mars Science Laboratory relative humidity observations : Initial results
  • 2014
  • In: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:9, s. 2132-2147
  • Journal article (peer-reviewed)abstract
    • The Mars Science Laboratory (MSL) made a successful landing at Gale crater early August 2012. MSL has an environmental instrument package called the Rover Environmental Monitoring Station (REMS) as a part of its scientific payload. REMS comprises instrumentation for the observation of atmospheric pressure, temperature of the air, ground temperature, wind speed and direction, relative humidity (REMS-H), and UV measurements. We concentrate on describing the REMS-H measurement performance and initial observations during the first 100 MSL sols as well as constraining the REMS-H results by comparing them with earlier observations and modeling results. The REMS-H device is based on polymeric capacitive humidity sensors developed by Vaisala Inc., and it makes use of transducer electronics section placed in the vicinity of the three humidity sensor heads. The humidity device is mounted on the REMS boom providing ventilation with the ambient atmosphere through a filter protecting the device from airborne dust. The final relative humidity results appear to be convincing and are aligned with earlier indirect observations of the total atmospheric precipitable water content. The water mixing ratio in the atmospheric surface layer appears to vary between 30 and 75 ppm. When assuming uniform mixing, the precipitable water content of the atmosphere is ranging from a few to six precipitable micrometers.
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  • Harri, A.-M., et al. (author)
  • Pressure observations by the Curiosity rover : Initial results
  • 2014
  • In: Journal of Geophysical Research - Planets. - : John Wiley & Sons. - 2169-9097 .- 2169-9100. ; 119:1, s. 82-92
  • Journal article (peer-reviewed)abstract
    • REMS-P, the pressure measurement subsystem of the Mars Science Laboratory (MSL) Rover Environmental Measurement Station (REMS), is performing accurate observations of the Martian atmospheric surface pressure. It has demonstrated high data quality and good temporal coverage, carrying out the first in situ pressure observations in the Martian equatorial regions. We describe the REMS-P initial results by MSL mission sol 100 including the instrument performance and data quality and illustrate some initial interpretations of the observed features. The observations show both expected and new phenomena at various spatial and temporal scales, e.g., the gradually increasing pressure due to the advancing Martian season signals from the diurnal tides as well as various local atmospheric phenomena and thermal vortices. Among the unexpected new phenomena discovered in the pressure data are a small regular pressure drop at every sol and pressure oscillations occurring in the early evening. We look forward to continued high-quality observations by REMS-P, extending the data set to reveal characteristics of seasonal variations and improved insights into regional and local phenomena. Key Points The performance and data quality of the REMS / MSL pressure observations. MSL pressure observations exhibit local phenomena of the Gale crater area. Small pressure oscillations possibly linked to gravity waves. ©2013. American Geophysical Union. All Rights Reserved.
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  • Vaughan, A., et al. (author)
  • Regolith of the Crater Floor Units, Jezero Crater, Mars : Textures, Composition, and Implications for Provenance
  • 2023
  • In: Journal of Geophysical Research - Planets. - : John Wiley and Sons Inc. - 2169-9097 .- 2169-9100. ; 128:3
  • Journal article (peer-reviewed)abstract
    • A multi-instrument study of the regolith of Jezero crater floor units by the Perseverance rover has identified three types of regolith: fine-grained, coarse-grained, and mixed-type. Mastcam-Z, Wide Angle Topographic Sensor for Operations and eNgineering, and SuperCam Remote Micro Imager were used to characterize the regolith texture, particle size, and roundedness where possible. Mastcam-Z multispectral and SuperCam laser-induced breakdown spectroscopy data were used to constrain the composition of the regolith types. Fine-grained regolith is found surrounding bedrock and boulders, comprising bedforms, and accumulating on top of rocks in erosional depressions. Spectral and chemical data show it is compositionally consistent with pyroxene and a ferric-oxide phase. Coarse-grained regolith consists of 1–2 mm well-sorted gray grains that are found concentrated around the base of boulders and bedrock, and armoring bedforms. Its chemistry and spectra indicate it is olivine-bearing, and its spatial distribution and roundedness indicate it has been transported, likely by saltation-induced creep. Coarse grains share similarities with the olivine grains observed in the Séítah formation bedrock, making that unit a possible source for these grains. Mixed-type regolith contains fine- and coarse-grained regolith components and larger rock fragments. The rock fragments are texturally and spectrally similar to bedrock within the Máaz and Séítah formations, indicating origins by erosion from those units, although they could also be a lag deposit from erosion of an overlying unit. The fine- and coarse-grained types are compared to their counterparts at other landing sites to inform global, regional, and local inputs to regolith formation within Jezero crater. The regolith characterization presented here informs the regolith sampling efforts underway by Perseverance. © 2023. The Authors.
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  • Guzewich, Scott D., et al. (author)
  • Mars Science Laboratory Observations of the 2018/Mars Year 34 Global Dust Storm
  • 2019
  • In: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 46:1, s. 71-79
  • Journal article (peer-reviewed)abstract
    • Mars Science Laboratory Curiosity rover observations of the 2018/Mars year 34 global/planet‐encircling dust storm represent the first in situ measurements of a global dust storm with dedicated meteorological sensors since the Viking Landers. The Mars Science Laboratory team planned and executed a science campaign lasting approximately 100 Martian sols to study the storm involving an enhanced cadence of environmental monitoring using the rover's meteorological sensors, cameras, and spectrometers. Mast Camera 880‐nm optical depth reached 8.5, and Rover Environmental Monitoring Station measurements indicated a 97% reduction in incident total ultraviolet solar radiation at the surface, 30K reduction in diurnal range of air temperature, and an increase in the semidiurnal pressure tide amplitude to 40 Pa. No active dust‐lifting sites were detected within Gale Crater, and global and local atmospheric dynamics were drastically altered during the storm. This work presents an overview of the mission's storm observations and initial results.
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  • Bach, D, et al. (author)
  • Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6
  • 2005
  • In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:9, s. 2685-2693
  • Journal article (peer-reviewed)abstract
    • The primary gene mutated in Charcot-Marie-Tooth type 2A is mitofusin-2 (Mfn2). Mfn2 encodes a mitochondrial protein that participates in the maintenance of the mitochondrial network and that regulates mitochondrial metabolism and intracellular signaling. The potential for regulation of human Mfn2 gene expression in vivo is largely unknown. Based on the presence of mitochondrial dysfunction in insulin-resistant conditions, we have examined whether Mfn2 expression is dysregulated in skeletal muscle from obese or nonobese type 2 diabetic subjects, whether muscle Mfn2 expression is regulated by body weight loss, and the potential regulatory role of tumor necrosis factor (TNF)α or interleukin-6. We show that mRNA concentration of Mfn2 is decreased in skeletal muscle from both male and female obese subjects. Muscle Mfn2 expression was also reduced in lean or in obese type 2 diabetic patients. There was a strong negative correlation between the Mfn2 expression and the BMI in nondiabetic and type 2 diabetic subjects. A positive correlation between the Mfn2 expression and the insulin sensitivity was also detected in nondiabetic and type 2 diabetic subjects. To determine the effect of weight loss on Mfn2 mRNA expression, six morbidly obese subjects were subjected to weight loss by bilio-pancreatic diversion. Mean expression of muscle Mfn2 mRNA increased threefold after reduction in body weight, and a positive correlation between muscle Mfn2 expression and insulin sensitivity was again detected. In vitro experiments revealed an inhibitory effect of TNFα or interleukin-6 on Mfn2 expression in cultured cells. We conclude that body weight loss upregulates the expression of Mfn2 mRNA in skeletal muscle of obese humans, type 2 diabetes downregulates the expression of Mfn2 mRNA in skeletal muscle, Mfn2 expression in skeletal muscle is directly proportional to insulin sensitivity and is inversely proportional to the BMI, TNFα and interleukin-6 downregulate Mfn2 expression and may participate in the dysregulation of Mfn2 expression in obesity or type 2 diabetes, and the in vivo modulation of Mfn2 mRNA levels is an additional level of regulation for the control of muscle metabolism and could provide a molecular mechanism for alterations in mitochondrial function in obesity or type 2 diabetes.
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  • Gómez-Elvira, J., et al. (author)
  • REMS : The environmental sensor suite for the Mars Science Laboratory rover
  • 2012
  • In: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 170:1-4, s. 583-640
  • Journal article (peer-reviewed)abstract
    • The Rover Environmental Monitoring Station (REMS) will investigate environmental factors directly tied to current habitability at the Martian surface during the Mars Science Laboratory (MSL) mission. Three major habitability factors are addressed by REMS: the thermal environment, ultraviolet irradiation, and water cycling. The thermal environment is determined by a mixture of processes, chief amongst these being the meteorological. Accordingly, the REMS sensors have been designed to record air and ground temperatures, pressure, relative humidity, wind speed in the horizontal and vertical directions, as well as ultraviolet radiation in different bands. These sensors are distributed over the rover in four places: two booms located on the MSL Remote Sensing Mast, the ultraviolet sensor on the rover deck, and the pressure sensor inside the rover body. Typical daily REMS observations will collect 180 minutes of data from all sensors simultaneously (arranged in 5 minute hourly samples plus 60 additional minutes taken at times to be decided during the course of the mission). REMS will add significantly to the environmental record collected by prior missions through the range of simultaneous observations including water vapor; the ability to take measurements routinely through the night; the intended minimum of one Martian year of observations; and the first measurement of surface UV irradiation. In this paper, we describe the scientific potential of REMS measurements and describe in detail the sensors that constitute REMS and the calibration procedures. © 2012 Springer Science+Business Media B.V.
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  • Korablev, O., et al. (author)
  • The Atmospheric Chemistry Suite (ACS) of Three Spectrometers for the ExoMars 2016 Trace Gas Orbiter
  • 2018
  • In: Space Science Reviews. - : Springer. - 0038-6308 .- 1572-9672. ; 214:1
  • Journal article (peer-reviewed)abstract
    • The Atmospheric Chemistry Suite (ACS) package is an element of the Russian contribution to the ESA-Roscosmos ExoMars 2016 Trace Gas Orbiter (TGO) mission. ACS consists of three separate infrared spectrometers, sharing common mechanical, electrical, and thermal interfaces. This ensemble of spectrometers has been designed and developed in response to the Trace Gas Orbiter mission objectives that specifically address the requirement of high sensitivity instruments to enable the unambiguous detection of trace gases of potential geophysical or biological interest. For this reason, ACS embarks a set of instruments achieving simultaneously very high accuracy (ppt level), very high resolving power (>10,000) and large spectral coverage (0.7 to 17 μm—the visible to thermal infrared range). The near-infrared (NIR) channel is a versatile spectrometer covering the 0.7–1.6 μm spectral range with a resolving power of ∼20,000. NIR employs the combination of an echelle grating with an AOTF (Acousto-Optical Tunable Filter) as diffraction order selector. This channel will be mainly operated in solar occultation and nadir, and can also perform limb observations. The scientific goals of NIR are the measurements of water vapor, aerosols, and dayside or night side airglows. The mid-infrared (MIR) channel is a cross-dispersion echelle instrument dedicated to solar occultation measurements in the 2.2–4.4 μm range. MIR achieves a resolving power of >50,000. It has been designed to accomplish the most sensitive measurements ever of the trace gases present in the Martian atmosphere. The thermal-infrared channel (TIRVIM) is a 2-inch double pendulum Fourier-transform spectrometer encompassing the spectral range of 1.7–17 μm with apodized resolution varying from 0.2 to 1.3 cm−1. TIRVIM is primarily dedicated to profiling temperature from the surface up to ∼60 km and to monitor aerosol abundance in nadir. TIRVIM also has a limb and solar occultation capability. The technical concept of the instrument, its accommodation on the spacecraft, the optical designs as well as some of the calibrations, and the expected performances for its three channels are described.
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  • Renno, N.O., et al. (author)
  • Ground-atmosphere interactions at Gale
  • 2013
  • Conference paper (peer-reviewed)abstract
    • We analyze variations in environmental parameters and regolith properties along Curiosity’s track to determine the possible causes of an abrupt change in the thermal properties of the ground and the atmosphere observed around Sol 120, as the rover transitioned from an area of sandy soil (Rocknest) to an area of fractured bedrock terrain (Yellowknife). Curiosity is instrumented with the Rover Environmental Monitoring Station (REMS) and the Dynamic Albedo of Neutrons (DAN) sensors to measure the air temperature, the ground temperature, and the hydrogen content of the shallow subsurface along Curiosity’s track. Analysis of the REMS data is used to estimate the regolith’s heat budget. This analysis suggests that the abrupt decrease in the ground and atmosphere temperature and the difference between ground and air temperatures observed around Sol 120 is likely caused by an increase in the soil thermal inertia. The changes in thermal inertia have been known for some time so confirming this by the REMS package provides ground truthing. A new unexpected finding is that the regolith water content, as indicated by DAN’s detection of hydrogen content, is higher in the Yellowknife soil. Another interesting finding at this site are the holes and other signs of recent geological activity in the area of fractured terrain that may reflect large volumetric variations and facilitate gas exchange between the ground and atmosphere. Near-surface volumetric changes in soil and bedrock could reflect changes in the volume of subsurface H2O, or in the partitioning of H2O among its three phases. Volume increases could also result from salt crystal growth in rock pores and soil pores associated with the adsorption of water vapor. Crystallization in pores is a significant weathering process on Earth; it could well be active on Mars. Salts also inhibits the exchange of moisture between the ground and the atmosphere, and cements the soils of arid places such as in the McMurdo Dry Valleys in Antarctica. Indeed, salts might be responsible for the ubiquitous martian duricrust. More importantly, salt crusts have the potential to create pockets of wet regolith in the shallow martian subsurface that could be habitable. A better understanding of ground-atmosphere interactions has the potential to shed new light into aqueous processes in the shallow martian subsurface.
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  • Rodriguez-Cuenca, S., et al. (author)
  • Allostatic hypermetabolic response in PGC1 alpha/beta heterozygote mouse despite mitochondrial defects
  • 2021
  • In: Faseb Journal. - 0892-6638. ; 35:9
  • Journal article (peer-reviewed)abstract
    • Aging, obesity, and insulin resistance are associated with low levels of PGC1 alpha and PGC1 beta coactivators and defective mitochondrial function. We studied mice deficient for PGC1 alpha and PGC1 beta [double heterozygous (DH)] to investigate their combined pathogenic contribution. Contrary to our hypothesis, DH mice were leaner, had increased energy dissipation, a pro-thermogenic profile in BAT and WAT, and improved carbohydrate metabolism compared to wild types. WAT showed upregulation of mitochondriogenesis/oxphos machinery upon allelic compensation of PGC1 alpha 4 from the remaining allele. However, DH mice had decreased mitochondrial OXPHOS and biogenesis transcriptomes in mitochondria-rich organs. Despite being metabolically healthy, mitochondrial defects in DH mice impaired muscle fiber remodeling and caused qualitative changes in the hepatic lipidome. Our data evidence first the existence of organ-specific compensatory allostatic mechanisms are robust enough to drive an unexpected phenotype. Second, optimization of adipose tissue bioenergetics is sufficient to maintain a healthy metabolic phenotype despite a broad severe mitochondrial dysfunction in other relevant metabolic organs. Third, the decrease in PGC1s in adipose tissue of obese and diabetic patients is in contrast with the robustness of the compensatory upregulation in the adipose of the DH mice.
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  • Romero, M., et al. (author)
  • TP53INP2 regulates adiposity by activating β-catenin through autophagy-dependent sequestration of GSK3β
  • 2018
  • In: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 20:4, s. 443-454
  • Journal article (peer-reviewed)abstract
    • Excessive fat accumulation is a major risk factor for the development of type 2 diabetes mellitus and other common conditions, including cardiovascular disease and certain types of cancer. Here, we identify a mechanism that regulates adiposity based on the activator of autophagy TP53INP2. We report that TP53INP2 is a negative regulator of adipogenesis in human and mouse preadipocytes. In keeping with this, TP53INP2 ablation in mice caused enhanced adiposity, which was characterized by greater cellularity of subcutaneous adipose tissue and increased expression of master adipogenic genes. TP53INP2 modulates adipogenesis through autophagy-dependent sequestration of GSK3β into late endosomes. GSK3β sequestration was also dependent on ESCRT activity. As a result, TP53INP2 promotes greater β-catenin levels and induces the transcriptional activity of TCF/LEF transcription factors. These results demonstrate a link between autophagy, sequestration of GSK3β into late endosomes and inhibition of adipogenesis in vivo. © 2018 The Author(s).
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  • Conrad, P.G., et al. (author)
  • Environmental Dynamics and the Habitability Potential at Gale Crater, Mars
  • 2013
  • Conference paper (peer-reviewed)abstract
    • The assessment of environmental habitability potential involves measurement of the chemical and physical attributes of the system as well as their dynamic interplay. The environmental dynamics describe the availability of both energy sources and raw materials for meeting the requirements of organisms and for altering the environment. Energetic exchange can also determine the preservation potential for organic materials in the rock record. During its first year at Gale Crater, the Mars Science Laboratory payload has directly measured the chemistry and physical attributes, e.g., temperature, humidity, radiation, pressure, etc. of the martian atmosphere. Curiosity has also acquired chemical and mineralogical data, both from a wind drift deposit of fines and from two examples of a sedimentary rock formation in a region of Gale Crater called Yellowknife Bay, some 445 meters to the east of Bradbury Landing, where Curiosity initially touched down. These data enabled inferences to be made regarding depositional environment and past habitability potential at Gale Crater. The rock chemistry data reveal signs of aqueous interaction i.e., H2O, OH and H2 and sufficient elemental basis (C, H, O, S and possibly N) for plausible nutrient supply, should Mars have ever had autotrophic prokaryotes to exploit it, and a range of redox conditions tolerable to Earth microbes is indicated by the presence of clay minerals. Curiosity’s observations of the chemical, physical and geologic features of Yellowknife Bay point to a formerly habitable environment.
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  • Guzewich, Scott D., et al. (author)
  • The Vertical Dust Profile over Gale Crater, Mars
  • 2017
  • In: Journal of Geophysical Research - Planets. - : American Geophysical Union (AGU). - 2169-9097 .- 2169-9100. ; 122:12, s. 2779-2792
  • Journal article (peer-reviewed)abstract
    • We create a vertically coarse, but complete, vertical profile of dust mixing ratio from the surface to the upper atmosphere over Gale Crater, Mars, using the frequent joint atmospheric observations of the orbiting Mars Climate Sounder (MCS) and the Mars Science Laboratory (MSL) Curiosity rover. Using these data and an estimate of planetary boundary layer (PBL) depth from the MarsWRF general circulation model, we divide the vertical column into three regions. The first region is the Gale Crater PBL, the second is the MCS-sampled region, and the third is between these first two. We solve for a well-mixed dust mixing ratio within this third (middle) layer of atmosphere to complete the profile.We identify a unique seasonal cycle of dust within each atmospheric layer. Within the Gale PBL, dust mixing ratio maximizes near southern hemisphere summer solstice (Ls = 270°) and minimizes near winter solstice (Ls = 90-100°) with a smooth sinusoidal transition between them. However, the layer above Gale Crater and below the MCS-sampled region more closely follows the global opacity cycle and has a maximum in opacity near Ls = 240° and exhibits a local minimum (associated with the “solsticial pause” in dust storm activity) near Ls = 270°. With knowledge of the complete vertical dust profile, we can also assess the frequency of high-altitude dust layers over Gale. We determine that 36% of MCS profiles near Gale Crater contain an “absolute” high-altitude dust layer wherein the dust mixing ratio is the maximum in the entire vertical column.
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  • Lanza, Nina L., et al. (author)
  • Oxidation of manganese in an ancient aquifer, Kimberley formation, Gale crater, Mars
  • 2016
  • In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 43:14, s. 7398-7407
  • Journal article (peer-reviewed)abstract
    • The Curiosity rover observed high Mn abundances (>25wt % MnO) in fracture-filling materials that crosscut sandstones in the Kimberley region of Gale crater, Mars. The correlation between Mn and trace metal abundances plus the lack of correlation between Mn and elements such as S, Cl, and C, reveals that these deposits are Mn oxides rather than evaporites or other salts. On Earth, environments that concentrate Mn and deposit Mn minerals require water and highly oxidizing conditions; hence, these findings suggest that similar processes occurred on Mars. Based on the strong association between Mn-oxide deposition and evolving atmospheric dioxygen levels on Earth, the presence of these Mn phases on Mars suggests that there was more abundant molecular oxygen within the atmosphere and some groundwaters of ancient Mars than in the present day
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  • Cockell, Charles S., et al. (author)
  • Subsurface scientific exploration of extraterrestrial environments (MINAR 5) : analogue science, technology and education in the Boulby Mine, UK
  • 2019
  • In: International Journal of Astrobiology. - : Cambridges Institutes Press. - 1473-5504 .- 1475-3006. ; 18:2, s. 157-182
  • Journal article (peer-reviewed)abstract
    • The deep subsurface of other planetary bodies is of special interest for robotic and human exploration. The subsurface provides access to planetary interior processes, thus yielding insights into planetary formation and evolution. On Mars, the subsurface might harbour the most habitable conditions. In the context of human exploration, the subsurface can provide refugia for habitation from extreme surface conditions. We describe the fifth Mine Analogue Research (MINAR 5) programme at 1 km depth in the Boulby Mine, UK in collaboration with Spaceward Bound NASA and the Kalam Centre, India, to test instruments and methods for the robotic and human exploration of deep environments on the Moon and Mars. The geological context in Permian evaporites provides an analogue to evaporitic materials on other planetary bodies such as Mars. A wide range of sample acquisition instruments (NASA drills, Small Planetary Impulse Tool (SPLIT) robotic hammer, universal sampling bags), analytical instruments (Raman spectroscopy, Close-Up Imager, Minion DNA sequencing technology, methane stable isotope analysis, biomolecule and metabolic life detection instruments) and environmental monitoring equipment (passive air particle sampler, particle detectors and environmental monitoring equipment) was deployed in an integrated campaign. Investigations included studying the geochemical signatures of chloride and sulphate evaporitic minerals, testing methods for life detection and planetary protection around human-tended operations, and investigations on the radiation environment of the deep subsurface. The MINAR analogue activity occurs in an active mine, showing how the development of space exploration technology can be used to contribute to addressing immediate Earth-based challenges. During the campaign, in collaboration with European Space Agency (ESA), MINAR was used for astronaut familiarization with future exploration tools and techniques. The campaign was used to develop primary and secondary school and primary to secondary transition curriculum materials on-site during the campaign which was focused on a classroom extra vehicular activity simulation.
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  • Enrique-Tarancon, G, et al. (author)
  • Substrates of semicarbazide-sensitive amine oxidase co-operate with vanadate to stimulate tyrosine phosphorylation of insulin-receptor-substrate proteins, phosphoinositide 3-kinase activity and GLUT4 translocation in adipose cells
  • 2000
  • In: Biochemical Journal. - 0264-6021. ; 350:1, s. 171-180
  • Journal article (peer-reviewed)abstract
    • It has been shown that the combination of benzylamine or tyramine and low concentrations of vanadate markedly stimulates glucose transport in rat adipocytes by a mechanism that requires semicarbazide-sensitive amine oxidase (SSAO) activity and H(2)O(2) formation. Here we have further analysed the insulin-like effects of the combination of SSAO substrates and vanadate and we have studied the signal-transduction pathway activated in rat adipocytes. We found that several SSAO substrates (benzylamine, tyramine, methylamine, n-decylamine, histamine, tryptamine or beta-phenylethylamine), in combination with low concentrations of vanadate, stimulate glucose transport in isolated rat adipocytes. Furthermore, SSAO substrates together with vanadate stimulated the recruitment of GLUT4 to the cell surface in isolated rat adipocytes. Benzylamine plus vanadate also stimulated glucose transport and GLUT4 translocation in 3T3-L1 adipocytes. Benzylamine or tyramine in combination with vanadate potently stimulated the tyrosine phosphorylation of both insulin receptor substrate (IRS)-1 and IRS-3. In contrast, benzylamine and vanadate caused only a weak stimulation of insulin receptor kinase. Benzylamine or tyramine in combination with vanadate also stimulated phosphoinositide 3-kinase activity; wortmannin abolished the stimulatory effect of benzylamine and vanadate on glucose transport in adipose cells. Furthermore, the administration of benzylamine and vanadate in vivo caused a rapid lowering of plasma glucose levels, which took place in the absence of alterations in plasma insulin. On the basis of these results we propose that SSAO activity regulates glucose transport in adipocytes. SSAO oxidative activity stimulates glucose transport via the translocation of GLUT4 carriers to the cell surface, resulting from a potent tyrosine phosphorylation of IRS-1 and IRS-3 and phosphoinositide 3-kinase activation. Our results also indicate that substrates of SSAO might regulate glucose disposal in vivo.
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  • Freissinet, C., et al. (author)
  • Organic molecules in the Sheepbed Mudstone, Gale Crater, Mars
  • 2015
  • In: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 120:3, s. 495-514
  • Journal article (peer-reviewed)abstract
    • The Sample Analysis at Mars (SAM) instrument [Mahaffy et al., 2012] onboard the Mars Science Laboratory (MSL) Curiosity rover is designed to conduct inorganic and organic chemical analyses of the atmosphere and the surface regolith and rocks to help evaluate the past and present habitability potential of Mars at Gale Crater [Grotzinger et al., 2012]. Central to this task is the development of an inventory of any organic molecules present to elucidate processes associated with their origin, diagenesis, concentration and long-term preservation. This will guide the future search for biosignatures [Summons et al., 2011]. Here we report the definitive identification of chlorobenzene (150–300 parts per billion by weight (ppbw)) and C2 to C4 dichloroalkanes (up to 70 ppbw) with the SAM gas chromatograph mass spectrometer (GCMS), and detection of chlorobenzene in the direct evolved gas analysis (EGA) mode, in multiple portions of the fines from the Cumberland drill hole in the Sheepbed mudstone at Yellowknife Bay. When combined with GCMS and EGA data from multiple scooped and drilled samples, blank runs and supporting laboratory analog studies, the elevated levels of chlorobenzene and the dichloroalkanes cannot be solely explained by instrument background sources known to be present in SAM. We conclude that these chlorinated hydrocarbons are the reaction products of martian chlorine and organic carbon derived from martian sources (e.g. igneous, hydrothermal, atmospheric, or biological) or exogenous sources such as meteorites, comets or interplanetary dust particles.
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33.
  • Gõmez-Elvira, Javier, et al. (author)
  • Curiosity's rover environmental monitoring station : Overview of the first 100 sols
  • 2014
  • In: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:7, s. 1680-1688
  • Journal article (peer-reviewed)abstract
    • In the first 100 Martian solar days (sols) of the Mars Science Laboratory mission, the Rover Environmental Monitoring Station (REMS) measured the seasonally evolving diurnal cycles of ultraviolet radiation, atmospheric pressure, air temperature, ground temperature, relative humidity, and wind within Gale Crater on Mars. As an introduction to several REMS-based articles in this issue, we provide an overview of the design and performance of the REMS sensors and discuss our approach to mitigating some of the difficulties we encountered following landing, including the loss of one of the two wind sensors. We discuss the REMS data set in the context of other Mars Science Laboratory instruments and observations and describe how an enhanced observing strategy greatly increased the amount of REMS data returned in the first 100 sols, providing complete coverage of the diurnal cycle every 4 to 6 sols. Finally, we provide a brief overview of key science results from the first 100 sols. We found Gale to be very dry, never reaching saturation relative humidities, subject to larger diurnal surface pressure variations than seen by any previous lander on Mars, air temperatures consistent with model predictions and abundant short timescale variability, and surface temperatures responsive to changes in surface properties and suggestive of subsurface layering. Key Points Introduction to the REMS results on MSL mission Overiview of the sensor information Overview of operational constraints
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34.
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35.
  • Lasue, J., et al. (author)
  • Martian Eolian Dust Probed by ChemCam
  • 2018
  • In: Geophysical Research Letters. - : John Wiley & Sons. - 0094-8276 .- 1944-8007. ; 45:20, s. 10968-10977
  • Journal article (peer-reviewed)abstract
    • The ubiquitous eolian dust on Mars plays important roles in the current sedimentary and atmospheric processes of the planet. The ChemCam instrument retrieves a consistent eolian dust composition at the submillimeter scale from every first laser shot on Mars targets. Its composition presents significant differences with the Aeolis Palus soils and the Bagnold dunes as it contains lower CaO and higher SiO2. The dust FeO and TiO2contents are also higher, probably associated with nanophase oxide components. The dust spectra show the presence of volatile elements (S and Cl), and the hydrogen content is similar to Bagnold sands but lower than Aeolis Palus soils. Consequently, the dust may be a contributor to the amorphous component of soils, but differences in composition indicate that the two materials are not equivalent.
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36.
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37.
  • Mompeán, C., et al. (author)
  • Prebiotic chemistry in neutral/reduced-alkaline gas-liquid interfaces
  • 2019
  • In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9:1
  • Journal article (peer-reviewed)abstract
    • The conditions for the potential abiotic formation of organic compounds from inorganic precursors have great implications for our understanding of the origin of life on Earth and for its possible detection in other environments of the Solar System. It is known that aerosol-interfaces are effective at enhancing prebiotic chemical reactions, but the roles of salinity and pH have been poorly investigated to date. Here, we experimentally demonstrate the uniqueness of alkaline aerosols as prebiotic reactors that produce an undifferentiated accumulation of a variety of multi-carbon biomolecules resulting from high-energy processes (in our case, electrical discharges). Using simulation experiments, we demonstrate that the detection of important biomolecules in tholins increases when plausible and particular local planetary environmental conditions are simulated. A greater diversity in amino acids, carboxylic acids, N-heterocycles, and ketoacids, such as glyoxylic and pyruvic acid, was identified in tholins synthetized from reduced and neutral atmospheres in the presence of alkaline aqueous aerosols than that from the same atmospheres but using neutral or acidic aqueous aerosols.
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38.
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39.
  • Ahlin, Sofie, 1985, et al. (author)
  • Metabolite Changes After Metabolic Surgery – Associations to Parameters Reflecting Glucose Homeostasis and Lipid Levels
  • 2021
  • In: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 12
  • Journal article (peer-reviewed)abstract
    • Aims: To test the hypothesis that adipose tissue gene expression patterns would be affected by metabolic surgery and we aimed to identify genes and metabolic pathways as well as metabolites correlating with metabolic changes following metabolic surgery. Materials and Methods: This observational study was conducted at the Obesity Unit at the Catholic University Hospital of the Sacred Heart in Rome, Italy. Fifteen patients, of which six patients underwent Roux-en-Y gastric bypass and nine patients underwent biliopancreatic diversion, were included. The participants underwent an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Small polar metabolites were analyzed with a two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). Gene expression analysis of genes related to metabolism of amino acids and fatty acids were analyzed in subcutaneous adipose tissue. All procedures were performed at study start and at follow-up (after 185.3 ± 72.9 days). Results: Twelve metabolites were significantly changed after metabolic surgery. Six metabolites were identified as 3-indoleacetic acid, 2-hydroxybutyric acid, valine, glutamic acid, 4-hydroxybenzeneacetic acid and alpha-tocopherol. The branched chain amino acids displayed a significant decrease together with a decrease in BCAT1 adipose tissue mRNA levels. Changes in the identified metabolites were associated to changes in lipid, insulin and glucose levels. Conclusions: Our study has identified metabolites and metabolic pathways that are altered by metabolic surgery and may be used as biomarkers for metabolic improvement. Copyright © 2021 Ahlin, Cefalo, Bondia-Pons, Trošt, Capristo, Marini, Romero, Zorzano, Gastaldelli, Mingrone and Nolan.
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40.
  • Andersen, Gregers Stig Tig, et al. (author)
  • The DEXLIFE study methods : identifying novel candidate biomarkers that predict progression to type 2 diabetes in high risk individuals
  • 2014
  • In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 106:2, s. 383-389
  • Journal article (peer-reviewed)abstract
    • The incidence of type 2 diabetes (T2D) is rapidly increasing worldwide and T2D is likely to affect 592 million people in 2035 if the current rate of progression is continued. Today, patients are diagnosed with T2D based on elevated blood glucose, either directly or indirectly (HbA1c). However, the information on disease progression is limited. Therefore, there is a need to identify novel early markers of glucose intolerance that reflect the underlying biology and the overall physiological, metabolic and clinical characteristics of progression towards diabetes. In the DEXLIFE study, several clinical cohorts provide the basis for a series of clinical, physiological and mechanistic investigations in combination with a range of--omic technologies to construct a detailed metabolic profile of high-risk individuals across multiple cohorts. In addition, an exercise and dietary intervention study is conducted, that will assess the impact on both plasma biomarkers and specific functional tissue-based markers. The DEXLIFE study will provide novel diagnostic and predictive biomarkers which may not only effectively detect the progression towards diabetes in high risk individuals but also predict responsiveness to lifestyle interventions known to be effective in the prevention of diabetes.
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41.
  • Aye, Cho-Cho, et al. (author)
  • CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells
  • 2023
  • In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:4
  • Journal article (peer-reviewed)abstract
    • CBL is rapidly phosphorylated upon insulin receptor activation. Mice whole body CBL depletion improved insulin sensitivity and glucose clearance; however, the precise mechanisms remain unknown. We depleted either CBL or its associated protein SORBS1/CAP independently in myocytes and assessed mitochondrial function and metabolism compared to control cells. CBL- and CAP-depleted cells showed increased mitochondrial mass with greater proton leak. Mitochondrial respiratory complex I activity and assembly into respirasomes were reduced. Proteome profiling revealed alterations in proteins involved in glycolysis and fatty acid degradation. Our findings demonstrate CBL/CAP pathway couples insulin signaling to efficient mitochondrial respiratory function and metabolism in muscle.
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42.
  •  
43.
  • Cockell, C.S., et al. (author)
  • Habitability : a review
  • 2016
  • In: Astrobiology. - : Mary Ann Liebert Inc. - 1531-1074 .- 1557-8070. ; 16:1, s. 89-117
  • Journal article (peer-reviewed)abstract
    • Habitability is a widely used word in the geoscience, planetary science, and astrobiology literature, but what does it mean? In this review on habitability, we define it as the ability of an environment to support the activity of at least one known organism. We adopt a binary definition of “habitability” and a “habitable environment.” An environment either can or cannot sustain a given organism. However, environments such as entire planets might be capable of supporting more or less species diversity or biomass compared with that of Earth. A clarity in understanding habitability can be obtained by defining instantaneous habitability as the conditions at any given time in a given environment required to sustain the activity of at least one known organism, and continuous planetary habitability as the capacity of a planetary body to sustain habitable conditions on some areas of its surface or within its interior over geological timescales. We also distinguish between surface liquid water worlds (such as Earth) that can sustain liquid water on their surfaces and interior liquid water worlds, such as icy moons and terrestrial-type rocky planets with liquid water only in their interiors. This distinction is important since, while the former can potentially sustain habitable conditions for oxygenic photosynthesis that leads to the rise of atmospheric oxygen and potentially complex multicellularity and intelligence over geological timescales, the latter are unlikely to. Habitable environments do not need to contain life. Although the decoupling of habitability and the presence of life may be rare on Earth, it may be important for understanding the habitability of other planetary bodies
  •  
44.
  • G. Trainer, Melissa, et al. (author)
  • Seasonal Variations in Atmospheric Composition as Measured in Gale Crater, Mars
  • 2019
  • In: Journal of Geophysical Research - Planets. - : John Wiley & Sons. - 2169-9097 .- 2169-9100. ; 124:11, s. 3000-3024
  • Journal article (peer-reviewed)abstract
    • The Sample Analysis at Mars (SAM) instrument onboard the Mars Science Laboratory Curiosity rover measures the chemical composition of major atmospheric species (CO2, N2, 40Ar, O2, and CO) through a dedicated atmospheric inlet. We report here measurements of volume mixing ratios in Gale Crater using the SAM quadrupole mass spectrometer, obtained over a period of nearly 5 years (3 Mars years) from landing. The observation period spans the northern summer of MY 31 and solar longitude (LS) of 175° through spring of MY 34, LS = 12°. This work expands upon prior reports of the mixing ratios measured by SAM QMS in the first 105 sols of the mission. The SAM QMS atmospheric measurements were taken periodically, with a cumulative coverage of four or five experiments per season on Mars. Major observations include the seasonal cycle of CO2, N2, and Ar, which lags approximately 20–40° of LS behind the pressure cycle driven by CO2 condensation and sublimation from the winter poles. This seasonal cycle indicates that transport occurs on faster timescales than mixing. The mixing ratio of O2 shows significant seasonal and interannual variability, suggesting an unknown atmospheric or surface process at work. The O2 measurements are compared to several parameters, including dust optical depth and trace CH4 measurements by Curiosity. We derive annual mean volume mixing ratios for the atmosphere in Gale Crater: CO2 = 0.951 (±0.003), N2 = 0.0259 (±0.0006), 40Ar = 0.0194 (±0.0004), O2 = 1.61 (±0.09) x 10‐3, and CO = 5.8 (±0.8) x 10‐4.
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45.
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46.
  • Gebhardt, C., et al. (author)
  • Fully Interactive and Refined Resolution Simulations of the Martian Dust Cycle by the MarsWRF Model
  • 2020
  • In: Journal of Geophysical Research - Planets. - : John Wiley & Sons. - 2169-9097 .- 2169-9100. ; 125:9
  • Journal article (peer-reviewed)abstract
    • The MarsWRF model is set up with fully interactive dust at 5° × 5° and 2° × 2 resolution. The latter allows for a better representation of topography and other surface properties. An infinite reservoir of surface dust is assumed for both resolutions. For 5° × 5°, surface dust lifting by wind stress takes place over broad areas, occurring in about 20% of the model’s grid cells. For 2° × 2°, it is more spatially restricted, occurring in less than 5% of the grid cells, and somewhat reminiscent of the corridors Acidalia‐Chryse, Utopia‐Isidis, and Arcadia‐West of Tharsis. The onset times of major dust storms ‐ large regional storms or global dust storm events (GDEs) ‐ do not exhibit much inter‐annual variability, typically occurring at around Ls 260°. However, their magnitude does show significant inter‐annual variability ‐ with only small regional storms in some years, large regional storms in others, and some years with GDEs ‐ owing to the interaction between major dust lifting regions at low latitudes. The latter is consistent with observed GDEs having several active dust lifting centers. The model’s dust distribution is found to better agree with observation‐based albedo and dust cover index maps for the 2° × 2° run. For the latter, there is also significant surface dust lifting by wind stress in the aphelion season that is largely confined to the Hellas basin. It has a recurring time pattern of 2‐7 sols, possibly resulting from the interaction between mid‐latitude baroclinic systems and local downslope flows.
  •  
47.
  • Hernández-Alvarez, María Isabel, et al. (author)
  • Deficient Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Causes Liver Disease
  • 2019
  • In: Cell. - : Cell Press. - 0092-8674 .- 1097-4172. ; 177:4, s. 881-895.e17
  • Journal article (peer-reviewed)abstract
    • Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was detected in liver biopsies from patients with non-alcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease.
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48.
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49.
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50.
  • Pla-García, J., et al. (author)
  • Preliminary Interpretation of the Meteorological Environment Through Mars Science Laboratory Rover Environmental Monitoring Station Observations and Mesoscale Modeling
  • 2014
  • Conference paper (peer-reviewed)abstract
    • In this study the Mars Regional AtmosphericModeling System (MRAMS) has been applied to theGale Crater region, the landing site of the Mars ScienceLaboratory (MSL) Rover Curiosity. The landingsite is at one of the lowest elevations in Gale,between the crater rim and the ~4 km high centralmound known as Mt. Sharp. As Curiosity headstoward its long term target of Mt. Sharp, the meteorologicalconditions are expected to change due to theincreasing influence of topographically-inducedthermal circulations that have been predicted by numerousprevious studies [1, 2, 3, 4]. The types ofperturbations of pressure, air and ground temperatureand wind measured by the Rover EnvironmentalMonitoring Station (REMS) [5] have never beenobserved at other locations and these data provide agreat opportunity to test the models at the most meteorologicalinteresting area measured to date. Weprovide a comparison of MRAMS predictions (pressure,air temperature, winds and ground temperature)to the REMS data available at the location of theRover for sols 21-25 (when first regular REMSmeasurements were obtained, Ls=163), sols 51-55(Ls=180), sol 215 (Ls=270) and sols 348-352 (Ls=0),in order to provide a baseline of model performance.
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