Moessbauer/XRF MIMOS Instrumentation and Operation During the 2012 Analog Field Test on Mauna Kea Volcano, Hawaii

Field testing and scientific investigations were conducted on the Mauna Kea Volcano, Hawaii, as part of the 2012 Moon and Mars Analog Mission Activities (MMAMA). Measurements were conducted using both stand-alone and rover-mounted instruments to determine the geophysical and geochemical properties of the field site, as well as provide operational constraints and science considerations for future robotic and human missions [1]. Reported here are the results from the two MIMOS instruments deployed as part of this planetary analog field test

An East to West Mineralogical Trend in Mars Exploration Rover Spirit Moessbauer Spectra of Home Plate

Home Plate is a light-toned plateau approx.90 m in diameter within the Inner Basin of the Columbia Hills in Gusev crater on Mars. It is the most extensive exposure of layered bedrock encountered by Spirit to date, and it is composed of clastic rocks of moderately altered alkali basalt composition, enriched in some highly volatile elements. Textural observations suggest an explosive origin and geochemical observations favor volcanism, probably a hydrovolcanic explosion [1]. Since it first arrived at Home Plate on sol 744, Spirit has circumnavigated the plateau (Fig. 1) and is now, since sol 1410, resting at its Winter Haven 3 location at the north end of Home Plate. Results: The MER Moessbauer spectrometers determine Fe oxidation states, identify Fe-bearing mineral phases and quantify the distribution of Fe among oxidation states and mineral phases [2]. Moessbauer spectra of Home Plate bedrock were obtained in five different locations from nine different targets (Fig. 1): Barnhill Ace, Posey Manager, and James Cool Papa Bell Stars at the northwest side of Home Plate; Pesapallo, June Emerson, and Elizabeth Emery on the east side; Texas Chili on the south side; Pecan Pie on the west side; and Chanute on the north side

Two Years of Chemical Sampling on Meridiani Planum by the Alpha Particle X-Ray Spectrometer Onboard the Mars Exploration Rover Opportunity

For over two terrestrial years, the Mars Exploration Rover Opportunity has been exploring the martian surface at Meridiani Planum using the Athena instrument payload [1], including the Alpha Particle X-Ray Spectrometer (APXS). The APXS has a small sensor head that is mounted on the robotic arm of the rover. The chemistry, mineralogy and morphology of selected samples were investigated by the APXS along with the Moessbauer Spectrometer (MB) and the Microscopic Imager (MI). The Rock Abrasion Tool (RAT) provided the possibility to dust and/or abrade rock surfaces down to several millimeters to expose fresh material for analysis. We report here on APXS data gathered along the nearly 6-kilometers long traverse in craters and plains of Meridiani

High temperature AlInP X-ray spectrometers

Two custom-made Al0.52In0.48P p+-i-n+ mesa photodiodes with different diameters (217 µm ± 15 µm and 409 µm ± 28 µm) and i layer thicknesses of 6 µm have been electrically characterised over the temperature range 0 °C to 100 °C. Each photodiode was then investigated as a high-temperature-tolerant photon counting X-ray detector by connecting it to a custom-made low-noise charge-sensitive preamplifier and illuminating it with an 55Fe radioisotope X-ray source (Mn Kα = 5.9 keV; Mn Kβ = 6.49 keV). At 100 °C, the best energy resolutions (full width at half maximum at 5.9 keV) achieved using the 217 µm ± 15 µm diameter photodiode and the 409 µm ±28 µm diameter photodiode were 1.31 keV ± 0.04 keV and 1.64 keV ±0.08 keV, respectively. Noise analysis of the system is presented. The dielectric dissipation factor of Al0.52In0.48P was estimated as a function of temperature, up to 100 °C. The results show the performance of the thickest Al0.52In0.48P X-ray detectors so far reported at high temperature. The work has relevance for the development of novel space science instrumentation for use in hot space environments and extreme terrestrial applications

Origin of acidic surface waters and the evolution of atmospheric chemistry on early Mars

Observations from in situ experiments and planetary orbiters have shown that the sedimentary rocks found at Meridiani Planum, Mars were formed in the presence of acidic surface waters. The water was thought to be brought to the surface by groundwater upwelling, and may represent the last vestiges of the widespread occurrence of liquid water on Mars. However, it is unclear why the surface waters were acidic. Here we use geochemical calculations, constrained by chemical and mineralogical data from the Mars Exploration Rover Opportunity, to show that Fe oxidation and the precipitation of oxidized iron (Fe^(3+)) minerals generate excess acid with respect to the amount of base anions available in the rocks present in outcrop. We suggest that subsurface waters of near-neutral pH and rich in Fe^(2+) were rapidly acidified as iron was oxidized on exposure to O_2 or photo-oxidized by ultraviolet radiation at the martian surface. Temporal variation in surface acidity would have been controlled by the availability of liquid water, and as such, low-pH fluids could be a natural consequence of the aridification of the martian surface. Finally, because iron oxidation at Meridiani would have generated large amounts of gaseous H_2, ultimately derived from the reduction of H_2O, we conclude that surface geochemical processes would have affected the redox state of the early martian atmosphere

Overexpression of S100A4 in human cancer cell lines resistant to methotrexate

Methotrexate is a chemotherapeutic drug that is used in therapy of a wide variety of cancers. The efficiency of treatment with this drug is compromised by the appearance of resistance. Combination treatments of MTX with other drugs that could modulate the expression of genes involved in MTX resistance would be an adequate strategy to prevent the development of this resistance. Methods: The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. A global comparison of all the studied cell lines was performed in order to find out differentially expressed genes in the majority of the MTX-resistant cells. S100A4 mRNA and protein levels were determined by RT-Real-Time PCR and Western blot, respectively. Functional validations of S100A4 were performed either by transfection of an expression vector for S100A4 or a siRNA against S100A4. Transfection of an expression vector encoding for β-catenin was used to inquire for the possible transcriptional regulation of S100A4 through the Wnt pathway. Results: S100A4 is overexpressed in five out of the seven MTX-resistant cell lines studied. Ectopic overexpression of this gene in HT29 sensitive cells augmented both the intracellular and extracellular S100A4 protein levels and caused desensitization toward MTX. siRNA against S100A4 decreased the levels of this protein and caused a chemosensitization in combined treatments with MTX. β-catenin overexpression experiments support a possible involvement of the Wnt signaling pathway in S100A4 transcriptional regulation in HT29 cells. Conclusions: S100A4 is overexpressed in many MTX-resistant cells. S100A4 overexpression decreases the sensitivity of HT29 colon cancer human cells to MTX, whereas its knockdown causes chemosensitization toward MTX. Both approaches highlight a role for S100A4 in MTX resistanc

Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations

BACKGROUND: Progressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP. OBJECTIVES: To determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS. METHODS: Multicenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity. RESULTS: The earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity. CONCLUSION: The PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials

Joining S100 proteins and migration:for better or for worse, in sickness and in health

The vast diversity of S100 proteins has demonstrated a multitude of biological correlations with cell growth, cell differentiation and cell survival in numerous physiological and pathological conditions in all cells of the body. This review summarises some of the reported regulatory functions of S100 proteins (namely S100A1, S100A2, S100A4, S100A6, S100A7, S100A8/S100A9, S100A10, S100A11, S100A12, S100B and S100P) on cellular migration and invasion, established in both culture and animal model systems and the possible mechanisms that have been proposed to be responsible. These mechanisms involve intracellular events and components of the cytoskeletal organisation (actin/myosin filaments, intermediate filaments and microtubules) as well as extracellular signalling at different cell surface receptors (RAGE and integrins). Finally, we shall attempt to demonstrate how aberrant expression of the S100 proteins may lead to pathological events and human disorders and furthermore provide a rationale to possibly explain why the expression of some of the S100 proteins (mainly S100A4 and S100P) has led to conflicting results on motility, depending on the cells used. © 2013 Springer Basel

The Wnt-dependent signaling pathways as target in oncology drug discovery

Our current understanding of the Wnt-dependent signaling pathways is mainly based on studies performed in a number of model organisms including, Xenopus, Drosophila melanogaster, Caenorhabditis elegans and mammals. These studies clearly indicate that the Wnt-dependent signaling pathways are conserved through evolution and control many events during embryonic development. Wnt pathways have been shown to regulate cell proliferation, morphology, motility as well as cell fate. The increasing interest of the scientific community, over the last decade, in the Wnt-dependent signaling pathways is supported by the documented importance of these pathways in a broad range of physiological conditions and disease states. For instance, it has been shown that inappropriate regulation and activation of these pathways is associated with several pathological disorders including cancer, retinopathy, tetra-amelia and bone and cartilage disease such as arthritis. In addition, several components of the Wnt-dependent signaling pathways appear to play important roles in diseases such as Alzheimer’s disease, schizophrenia, bipolar disorder and in the emerging field of stem cell research. In this review, we wish to present a focused overview of the function of the Wnt-dependent signaling pathways and their role in oncogenesis and cancer development. We also want to provide information on a selection of potential drug targets within these pathways for oncology drug discovery, and summarize current data on approaches, including the development of small-molecule inhibitors, that have shown relevant effects on the Wnt-dependent signaling pathways