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Human melanoma-associated retinopathy (MAR) antibodies alter the retinal ON-response of the monkey ERG in vivo.

PURPOSE: Melanoma-associated retinopathy (MAR) is a paraneoplastic condition that causes visual symptoms of night-blindness and photopsias. The electroretinogram (ERG) of MAR patients is characteristically abnormal in a way that implicates retinal depolarizing bipolar cell (DBC) dysfunction. Whether an injection of IgG from MAR patients into the vitreous of monkeys would alter the ERG acutely as a demonstration of a functional basis for patients' visual symptoms was explored. METHODS: MAR IgG was isolated from three visually symptomatic melanoma patients. Control IgG was from melanoma patients with no vision problems. The ERG was monitored after intravitreal injections into monkey eyes. One eye was injected with 2-amino-4-phosphonobutyric acid (APB), which is known to block DBC ON-pathway responses. Retinal immunocytochemistry was performed using fluorescein isothiocyanate-labeled goat anti-human IgG. RESULTS: Within 1 to 3 hours after MAR IgG injection, the ERG photopic b-wave was diminished, with far less effect on the a- and d-waves. These changes are characteristic of DBC dysfunction and were similar to the effects of APB. The scotopic ERG b-wave, which reflects activity of rod-driven DBCs, showed a loss of amplitude and threshold sensitivity after MAR IgG. Retinal immunocytochemistry with anti-IgG antibody showed IgG penetration throughout the retinal layers, but staining was not specific for a single type of retinal neuron. CONCLUSIONS: Intravitreal injection of human MAR IgG altered the monkey ERG acutely in ways that implicate functional disruption of retinal DBC signaling. These results support the hypothesis that MAR IgG circulating antibodies are responsible for the reported visual symptoms. Bipolar cells in the ON-pathway appear to be affected more than OFF-pathway bipolar cells of the cone pathway in this acute preparation.

Aminobutyrates↗

A matrix attachment region (MAR)-binding activity due to a p114 kilodalton protein is found only in human breast carcinomas and not in normal and benign breast disease tissues.

A M(r) 114,000 protein (p114) that specifically binds to nuclear matrix attachment DNA (matrix attachment region, MAR) from a breast carcinoma cell line SK-BR-3 was purified to near homogeneity. p114 strongly binds to a wild-type A+T-rich MAR probe with high unwinding propensity with a dissociation constant (Kd) of 10(-9), while it exhibits substantially reduced binding to a mutated A+T-rich non-MAR probe, which lacks unwinding propensity. This binding specificity and affinity is similar to the previously cloned thymocyte-associated MAR-binding protein SATB1. By Southwestern blot analysis, the MAR-binding activity of p114 is detectable in human breast carcinomas but is undetectable in normal breast tissues, benign breast diseases, and immortalized epithelial MCF-10A cells. Thus, the MAR-binding activity of p114 is not merely reflecting cell proliferation, but it strongly associates with breast carcinomas. The p114 MAR-binding activity was found in all 43 human breast carcinoma specimens tested, without exception. Much stronger p114 MAR-binding activity was detected in poorly differentiated than well-differentiated carcinomas. p114 may be a reliable diagnostic and possibly prognostic marker for breast cancer.

Base Sequence↗

Hydrothermal systems on Mars: an assessment of present evidence.

Hydrothermal processes have been suggested to explain a number of observations for Mars, including D/H ratios of water extracted from Martian meteorites, as a means for removing CO2 from the Martian atmosphere and sequestering it in the crust as carbonates, and as a possible origin for iron oxide-rich spectral units on the floors of some rifted basins (chasmata). There are numerous examples of Martian channels formed by discharges of subsurface water near potential magmatic heat sources, and hydrothermal processes have also been proposed as a mechanism for aquifer recharge needed to sustain long term erosion of sapping channels. The following geological settings have been identified as targets for ancient hydrothermal systems on Mars: channels located along the margins of impact crater melt sheets and on the slopes of ancient volcanoes; chaotic and fretted terranes where shallow subsurface heat sources are thought to have interacted with ground ice; and the floors of calderas and rifted basins (e.g. chasmata). On Earth, such geological environments are often a locus for hydrothermal mineralization. But we presently lack the mineralogical information needed for a definitive evaluation of hypotheses. A preferred tool for identifying minerals by remote sensing methods on Earth is high spatial resolution, hyperspectral, near-infrared spectroscopy, a technique that has been extensively developed by mineral explorationists. Future efforts to explore Mars for ancient hydrothermal systems would benefit from the application of methods developed by the mining industry to look for similar deposits on Earth. But Earth-based exploration models must be adapted to account for the large differences in the climatic and geological history of Mars. For example, it is likely that the early surface environment of Mars was cool, perhaps consistently below freezing, with the shallow portions of hydrothermal systems being dominated by magma-cryosphere interactions. Given the smaller gravitational field, declining atmospheric pressure, and widespread, permeable megaregolith on Mars, volatile outgassing and magmatic cooling would have been more effective than on Earth. Thus, hydrothermal systems are likely to have had much lower average surface temperatures than comparable geological settings on Earth. The likely predominance of basaltic crust on Mars suggests that hydrothermal fluids and associated deposits should be enriched in Fe, Mg, Si and Ca, with surficial deposits being dominated by lower temperature, mixed iron oxide and carbonate mineralogies.

Deuterium↗

Electrochemical approaches for chemical and biological analysis on Mars.

Obtaining in situ chemical data from planetary bodies such as Mars or Europa can present significant challenges. The one analytical technique that has many of the requisite characteristics to meet such a challenge is electroanalysis. Described here are three electroanalytical devices designed for in situ geochemical and biological analysis on Mars. The Mars Environmental Compatibility Assessment (MECA) was built and flight qualified for the now cancelled NASA Mars 2001 Lander. Part of MECA consisted of four "cells" containing arrays of electrochemical based sensors for measuring the ionic species in soil samples. A next-generation MECA, the Robotic Chemical Analysis Laboratory (RCAL), uses a carousel-type system to allow for greater customization of analytical procedures. A second instrument, proposed as part of the 2007 CryoScout mission, consists of a flow-through inorganic chemical analyzer (MICA). CryoScout is a torpedo-like device designed for subsurface investigation of the stratigraphic climate record embedded in Mars' north polar cap. As the CryoScout melts its way through the ice cap, MICA will collect and analyze the meltwater for a variety of inorganics and chemical parameters. By analyzing the chemistry locked in the layers of dust, salt, and ice, geologists will be able to determine the recent history of climate, water, and atmosphere on Mars and link it to the past. Finally, electroanalysis shows its abilities in the detection of possible microorganism on Mars or elsewhere in the solar system. To identify an unknown microorganism, one that may not even use Earth-type biochemistry, requires a detection scheme which makes minimal assumptions and looks for the most general features. Recent work has demonstrated that the use of an array of electrochemical sensors which monitors the changes in a solution via electrical conductivity, pH, and ion selective electrodes, can be used to detect minute chemical perturbations caused by the growth of bacteria and with the correct methodology provide unamibiguous detection of such life forms.

Chemistry Techniques, Analytical↗

Science strategy for human exploration of Mars.

The scientific objectives of Mars exploration can be framed within the overarching theme of exploring Mars as another home for life, both for evidence of past or present life on Mars, and as a potential future home for human life. The two major areas of research within this theme are: 1) determining the relationship between planetary evolution, climate change, and life, and 2) determining the habitability of Mars. Within this framework, this paper discusses the exploration objectives for exobiology, climatology and atmospheric science, geology, and martian resource assessment. Human exploration will proceed in four major phases: 1) Precursor missions which will obtain environmental knowledge necessary for human exploration, 2) Emplacement phase which includes the first few human landings where crews will explore the local area of the landing site; 3) Consolidation phase missions where a permanent base will be constructed and crews will be capable of detailed exploration over regional scales; 4) Utilization phase, in which a continuously occupied permanent Mars base exists and humans will be capable of detailed global exploration of the martian surface. The phases of exploration differ primarily in the range and capabilities of human mobility. In the emplacement phase, an unpressurized rover, similar to the Apollo lunar rover, will be used and will have a range of a few tens of kilometers. In the Consolidation phase, mobility will be via a pressurized all-terrain vehicle capable of expeditions from the base site of several weeks duration. In the Utilization phase, humans will be capable of several months long expeditions to any point on the surface of Mars using a suborbital rocket equipped with habitat, lab, and return vehicle. Because of human mobility limitations, it is important to extend the range and duration of exploration in all phases by using teleoperated rover vehicles. Site selection for human missions to Mars must consider the multi-decade time frame of these four phases. We suggest that operations in the first two phases be focused in the regional area containing the Coprates Quadrangle and adjacent areas.

Astronauts↗

Estimation and assessment of Mars contamination.

Since the beginning of the exploration of Mars, more than fourty years ago, thirty-six missions have been launched, including fifty-nine different space systems such as fly-by spacecraft, orbiters, cruise modules, landing or penetrating systems. Taking into account failures at launch, about three missions out of four have been successfully sent toward the Red Planet. The fact today is that Mars orbital environment includes orbiters and perhaps debris, and that its atmosphere and its surface include terrestrial compounds and dormant microorganisms. Coming from the UN Outer Space Treaty [United Nations Treaty on Principles Governing the Activities of States in the Exploration and Use of Outer Space, including the Moon and Other Celestial Bodies (the "Outer Space Treaty") referenced 610 UNTS 205 - resolution 2222(XXI) of December 1966] and according to the COSPAR planetary protection policy recommendations [COSPAR Planetary Protection Policy (20 October 2002), accepted by the Council and Bureau, as moved for adoption by SC F and PPP, prepared by the COSPAR/IAU Workshop on Planetary Protection, 4/02 with updates 10/0, 2002], Mars environment has to be preserved so as not to jeopardize the scientific investigations, and the level of terrestrial material brought on and around Mars theoretically has to comply with this policy. It is useful to evaluate what and how many materials, compounds and microorganisms are on Mars, to list what is in orbit and to identify where all these items are. Considering assumptions about materials, spores and gas location and dispersion on Mars, average contamination levels can be estimated. It is clear now that as long as missions are sent to other extraterrestrial bodies, it is not possible to keep them perfectly clean. Mars is one of the most concerned body, and the large number of missions achieved, on-going and planned now raise the question about its possible contamination, not necessarily from a biological point of view, but with respect to all types of contamination. Answering this question, will help to assess the potential effects of such contamination on scientific results and will address concerns relative to any ethical considerations about the contamination of other planets.

Containment of Biohazards↗

Self-sustaining Mars colonies utilizing the North Polar Cap and the Martian atmosphere.

A revolutionary new concept for the early establishment of robust, self-sustaining Martian colonies is described. The colonies would be located on the North Polar Cap of Mars and utilize readily available water ice and the CO2 Martian atmosphere as raw materials to produce all of the propellants, fuel, air, water, plastics, food, and other supplies needed by the colony. The colonists would live in thermally insulated large, comfortable habitats under the ice surface, fully shielded from cosmic rays. The habitats and supplies would be produced by a compact, lightweight (~4 metric tons) nuclear powered robotic unit termed ALPH (Atomic Liberation of Propellant and Habitat), which would land 2 years before the colonists arrived. Using a compact, lightweight 5 MW (th) nuclear reactor/steam turbine (1 MW(e)) power source and small process units (e.g., H2O electrolyzer, H2 and O2 liquefiers, methanator, plastic polymerizer, food producer, etc.) ALPH would stockpile many hundreds of tons of supplies in melt cavities under the ice, plus insulated habitats, to be in place and ready for use when the colonists landed. With the stockpiled supplies, the colonists would construct and operate rovers and flyers to explore the surface of Mars. ALPH greatly reduces the amount of Earth supplied material needed and enables large permanent colonies on Mars. It also greatly reduces human and mission risks and vastly increases the capability not only for exploration of the surrounding Martian surface, but also the ice cap itself. The North Polar Cap is at the center of the vast ancient ocean that covered much of the Martian Northern Hemisphere. Small, nuclear heated robotic probes would travel deep (1 km or more) inside the ice cap, collecting data on its internal structure, the composition and properties of the ancient Martian atmosphere, and possible evidence of ancient life forms (microfossils, traces of DNA, etc.) that were deposited either by wind or as remnants of the ancient ocean. Details of the ALPH system, which is based on existing technology, are presented. ALPH units could be developed and demonstrated on Earth ice sheets within a few years. An Earth-Mars space transport architecture is described, in which Mars produced propellant and supplies for return journeys to Earth would be lifted with relatively low DeltaV to Mars orbit, and from there transported back to Earth orbit, enabling faster and lower cost trips from Earth to Mars. The exploration capability and quality of life in a mature Martian colony of 500 persons located on the North Polar Cap is outlined.

Carbon Dioxide↗

Planetary protection and the search for life beneath the surface of Mars.

The search for traces of extinct and extant life on Mars will be extended to beneath the surface of the planet. Current data from Mars missions suggesting the presence of liquid water early in Mars' history and mathematical modeling of the fate of water on Mars imply that liquid water may exist deep beneath the surface of Mars. This leads to the hypothesis that life may exist deep beneath the Martian surface. One possible scenario to look for life on Mars involves a series of unmanned missions culminating with a manned mission drilling deep into the Martian subsurface (approximately 3Km), collecting samples, and conducting preliminary analyses to select samples for return to earth. This mission must address both forward and back contamination issues, and falls under planetary protection category V. Planetary protection issues to be addressed include provisions stating that the inevitable deposition of earth microbes by humans should be minimized and localized, and that earth microbes and organic material must not contaminate the Martian subsurface. This requires that the drilling equipment be sterilized prior to use. Further, the collection, containment and retrieval of the sample must be conducted such that the crew is protected and that any materials returning to earth are contained (i.e., physically and biologically isolated) and the chain of connection with Mars is broken.

Containment of Biohazards↗

Alteration processes in volcanic soils and identification of exobiologically important weathering products on Mars using remote sensing.

Determining the mineralogy of the Martian surface material provides information about the past and present environments on Mars which are an integral aspect of whether or not Mars was suitable for the origin of life. Mineral identification on Mars will most likely be achieved through visible-infrared remote sensing in combination with other analyses on landed missions. Therefore, understanding the visible and infrared spectral properties of terrestrial samples formed via processes similar to those thought to have occurred on Mars is essential to this effort and will facilitate site selection for future exobiology missions to Mars. Visible to infrared reflectance spectra are presented here for the fine-grained fractions of altered tephra/lava from the Haleakala summit basin on Maui, the Tarawera volcanic complex on the northern island of New Zealand, and the Greek Santorini island group. These samples exhibit a range of chemical and mineralogical compositions, where the primary minerals typically include plagioclase, pyroxene, hematite, and magnetite. The kind and abundance of weathering products varied substantially for these three sites due, in part, to the climate and weathering environment. The moist environments at Santorini and Tarawera are more consistent with postulated past environments on Mars, while the dry climate at the top of Haleakala is more consistent with the current Martian environment. Weathering of these tephra is evaluated by assessing changes in the leachable and immobile elements, and through detection of phyllosilicates and iron oxide/oxyhydroxide minerals. Identifying regions on Mars where phyllosilicates and many kinds of iron oxides/oxyhydroxides are present would imply the presence of water during alteration of the surface material. Tephra samples altered in the vicinity of cinder cones and steam vents contain higher abundances of phyllosilicates, iron oxides, and sulfates and may be interesting sites for exobiology.

Evolution, Planetary↗

Surface characteristics of spacecraft components affect the aggregation of microorganisms and may lead to different survival rates of bacteria on Mars landers.

Layers of dormant endospores of Bacillus subtilis HA101 were applied to eight different spacecraft materials and exposed to martian conditions of low pressure (8.5 mbar), low temperature (-10 degrees C), and high CO(2) gas composition and irradiated with a Mars-normal ultraviolet (UV-visible- near-infrared spectrum. Bacterial layers were exposed to either 1 min or 1 h of Mars-normal UV irradiation, which simulated clear-sky conditions on equatorial Mars (0.1 tau). When exposed to 1 min of Mars UV irradiation, the numbers of viable endospores of B. subtilis were reduced three to four orders of magnitude for two brands of aluminum (Al), stainless steel, chemfilm-treated Al, clear-anodized Al, and black-anodized Al coupons. In contrast, bacterial survival was reduced only one to two orders of magnitude for endospores on the non-metal materials astroquartz and graphite composite when bacterial endospores were exposed to 1 min of Mars UV irradiation. When bacterial monolayers were exposed to 1 h of Mars UV irradiation, no viable bacteria were recovered from the six metal coupons listed above. In contrast, bacterial survival was reduced only two to three orders of magnitude for spore layers on astroquartz and graphite composite exposed to 1 h of Mars UV irradiation. Scanning electron microscopy images of the bacterial monolayers on all eight spacecraft materials revealed that endospores of B. subtilis formed large aggregates of multilayered spores on astroquartz and graphite composite, but not on the other six spacecraft materials. It is likely that the formation of multilayered aggregates of endospores on astroquartz and graphite composite is responsible for the enhanced survival of bacterial cells on these materials.

Bacillus subtilis↗

Potassium ferrate [Fe(VI)] does not mediate self-sterilization of a surrogate Mars soil.

BACKGROUND: Martian soil is thought to be enriched with strong oxidants such as peroxides and/or iron in high oxidation states that might destroy biological materials. There is also a high flux of ultraviolet radiation at the surface of Mars. Thus, Mars may be inhospitable to life as we know it on Earth. We examined the hypothesis that if the soil of Mars contains ferrates [Fe(VI)], the strongest of the proposed oxidizing species, and also is exposed to high fluxes of UV radiation, it will be self-sterilizing. RESULTS: Under ambient conditions (25 degrees C, oxygen and water present) K2FeO4 mixed into sand mineralized some reactive organic molecules to CO2, while less reactive compounds were not degraded. Dried endospores of Bacillus subtilis incubated in a Mars surrogate soil comprised of dry silica sand containing 20% by weight K2FeO4 and under conditions similar to those now on Mars (extreme desiccation, cold, and a CO2-dominated atmosphere) were resistant to killing by the ferrate-enriched sand. Similar results were observed with permanganate. Spores in oxidant-enriched sand exposed to high fluxes of UV light were protected from the sporocidal activity of the radiation below about 5 mm depths. CONCLUSION: Based on our data and previously published descriptions of ancient but dormant life forms on Earth, we suggest that if entities resembling bacterial endospores were produced at some point by life forms on Mars, they might still be present and viable, given appropriate germination conditions. Endospores delivered to Mars on spacecraft would possibly survive and potentially compromise life detection experiments.

Bacillus subtilis↗

Preparing for Mars: the physiologic and medical challenges.

As the twentieth century closes, retrospectives cite the Apollo moon missions as one of the important events of the past 100 years. A trip to Mars, however, would be even more challenging and significant. A round-trip Mars journey would require nearly three years away from Earth, a significant leap in complexity compared to the two week long Moon trips or the record-breaking fourteen-month flight on Mir. What would be the physiologic and medical challenges of a Mars flight? Two key areas of physiology present the greatest potential problems--calcium metabolism and radiation exposure. Data from Mir missions show that bone loss continues in space despite an aggressive countermeasure program. Average losses were 0.35% per month, but some load bearing areas lost >1% per month. A 1% loss rate, if it continued unabated for 30 months, could produce osteoporosis. Smaller losses could still increase fracture risk. Some bone loss can be well tolerated, particularly if the bone can be regained after the mission. But the effectiveness of post-flight rehabilitation to restore the density and quality of bone after spaceflight is not well known. Bone loss estimates are based on continuous weightlessness exposure, but this is not a requirement for a Mars trip. Most of the time on a Mars trip will be spent in the 1/3 Earth's gravity environment on Mars, and either intermittent or continuous artificial gravity can be provided for the transit between planets (although at an engineering cost). The dosing of the gravity exposure (e.g. the level and duration), however, has not been established. Radiation protection also requires a balance between engineering cost and human health. Excessive shielding could add billions of dollars to the cost of a mission. Trips in interplanetary space, however, expose the crew to heavy high-energy particles from cosmic rays (HZE particles), which have a high linear energy transfer. This high energy leads to significant biological damage (e.g. chromosomal aberrations, cancer induction). A recent report from the Committee on Space Biology and Medicine notes that only one systematic study of cancer induction from high-energy particles has been conducted (using the mouse Harderian gland). Predictions of cancer risk and acceptable radiation exposure in space are extrapolated from minimal data. Other areas of physiology also present problems, such as muscle loss, cardiovascular deconditioning, and vestibular adaptation. Despite all the issues, however, a focussed, aggressive research program that uses the resources of the International Space Station should pave the way for mankind's greatest adventure--a trip to Mars.

Humans↗

The nanophase iron mineral(s) in Mars soil.

A series of surface-modified clays containing nanophase (np) iron oxide/oxyhydroxides of extremely small particle sizes, with total iron contents as high as found in Mars soil, were prepared by iron deposition on the clay surface from ferrous chloride solution. Comprehensive studies of the iron mineralogy in these "Mars-soil analogs" were conducted using chemical extractions, solubility analyses, pH and redox, x ray and electron diffractometry, electron microscopic imaging, specific surface area and particle size determinations, differential thermal analyses, magnetic properties characterization, spectral reflectance, and Viking biology simulation experiments. The clay matrix and the procedure used for synthesis produced nanophase iron oxides containing a certain proportion of divalent iron, which slowly converts to more stable, fully oxidized iron minerals. The clay acted as an effective matrix, both chemically and sterically, preventing the major part of the synthesized iron oxides from ripening, i.e., growing and developing larger crystals. The precipitated iron oxides appear as isodiametric or slightly elongated particles in the size range 1-10 nm, having large specific surface area. The noncrystalline nature of the iron compounds precipitated on the surface of the clay was verified by their complete extractability in oxalate. Lepidocrocite (gamma-FeOOH) was detected by selected area electron diffraction. It is formed from a double iron Fe(II)/Fe(III) hydroxy mineral such as "green rust," or ferrosic hydroxide. Magnetic measurements suggested that lepidocrocite converted to the more stable maghemite (gamma-Fe2O3) by mild heat treatment and then to nanophase hematite (alpha-Fe2O3) by extensive heat treatment. After mild heating, the iron-enriched clay became slightly magnetic, to the extent that it adheres to a hand-held magnet, as was observed with Mars soil. The chemical reactivity of the iron-enriched clays strongly resembles, and offers a plausible mechanism for, the somewhat puzzling observations of the Viking biology experiments. Their unique chemical reactivities are attributed to the combined catalytic effects of the iron oxide/oxyhydroxides and silicate phase surfaces. The reflectance spectrum of the clay-iron preparations in the visible range is generally similar to the reflectance curves of bright regions on Mars. This strengthens the evidence for the predominance of nanophase iron oxides/oxyhydroxides in Mars soil. The mode of formation of these nanophase iron oxides on Mars is still unknown. It is puzzling that despite the long period of time since aqueous weathering took place on Mars, they have not developed from their transitory stage to well-crystallized end-members. The possibility is suggested that these phases represent a continuously on-going, extremely slow weathering process.

Aluminum Silicates↗

High affinity MAR-DNA binding is a common property of murine and human mutant p53.

We recently reported that murine MethA mutant but not wild-type p53 specifically binds to MAR-DNA elements (MARs) with high affinity. Here we show that this DNA binding activity is exerted not only by MethA mutant p53 but also by other murine mutant p53 proteins isolated from the transformed murine BALB/c cell lines 3T3tx and T3T3 and differing in their conformational status. High affinity MAR-DNA binding was not restricted to the Xbal-IgE-MAR-DNA fragment from the murine immunoglobulin heavy chain gene enhancer locus [Cockerill et al. (1987): J Biol Chem 262:5394-5397] used in previous studies, as MethA p53 also specifically interacted with other A/T-rich bona fide MARs. Not only murine but also human mutant p53 proteins carrying the mutational hot spot amino acid exchanges 175Arg-->His, 273Arg-->Pro, or 273Arg-->His bound to the Xbal-IgE-MAR-DNA fragment. We therefore conclude that high affinity MAR-DNA binding is a property common to a variety of mutant p53 proteins.

3T3 Cells↗

Life on Mars? The Viking labeled release experiment.

Viking radiorespirometry ("Labeled Release" [LR]) experiments conducted on surface material obtained at two sites on Mars have produced results which on Earth would clearly establish the presence of microbial activity in the soil. However, two factors on Mars keep the question open. First, the intense UV flux striking Mars has given rise to several theories postulating the production of highly oxidative compounds. Such compounds might be responsible for the observed results. Second, the molecular analysis experiment has not found organic matter in the Mars surface material, and therefore, does not support the presence of roganisms. However, sensitivity limitations of the organic analysis instrument could permit as many as one million terrestrial type bacteria to go undetected. Terrestrial experiments with UV irradiation of Mars Analog Soil did not produce Mars type LR results. Gamma irradiation of silica gel did produce positive results, but not mimicking those on Mars. The life question remains open.

Carbon↗

Multivariate adaptive regression splines (MARS) in chromatographic quantitative structure-retention relationship studies.

The multivariate adaptive regression splines (MARS) methodology was applied to build quantitative structure-retention relationships (QSRRs). The response (dependent variable) in the MARS models consisted of the logarithms of the extrapolated retention factors (log k(w)) of 83 structurally diverse drugs on a Unisphere PBD column, using isocratic elutions at pH 11.7. A set of 266 molecular descriptors was used as predictor (independent) variables in the MARS model building. The optimal MARS model uses 34 basis functions to describe the retention and has acceptable predictive properties for new objects. The molecular descriptors included in the model describe hydrophobicity, molecular size, complexity, shape and polarisability. Some additional MARS models were created using alternative strategies. These include models with log P as the single predictor and models obtained with only the three most important molecular descriptors. The use of classification and regression trees (CART) as feature selection technique for predictor variables used in the MARS model was also investigated. Further, it is also studied whether allowing quadratic terms instead of interaction terms might lead to better MARS models.

Chromatography, Liquid↗

Mixed erythrocyte-spermatozoa antiglobulin reaction (MAR test) for IgA antisperm antibodies in subfertile males.

A mixed antiglobulin reaction (MAR test), using antibody-coated red cells and spermatozoa, has been used to detect the presence of either IgA or IgG on he surface of the spermatozoa. Group O Rh-positive red cells were sensitized with serum containing anti-D, which was partly IgA, though mainly IgG. Spermatozoa were added to the sensitized red cells and tested either with anti-IgA or anti-IgG. MAR (IgA) test results were negative or doubtful in 42 (44%) of 94 samples with positive or strongly positive MAR (IgG) tests. Positive MAR (IgA) tests showed a highly significant correlation with the presence of antisperm antibodies in seminal plasma. Significantly impaired sperm penetration of cervical mucus was demonstrated for 15 patients, 12 of whom had positive MAR (IgA) tests, whereas good sperm penetration was observed for 5 patients with negative or dubious MAR (IgA) tests; all 20 patients had strongly positive MAR (IgG) tests and positive serum antisperm antibody tests.

Autoantibodies↗

Economic evaluation and 1-year survival analysis of MARS in patients with alcoholic liver disease.

Objective of this study was to determine 1-year survival, costs and cost-effectiveness of the artificial liver support system Molecular Adsorbent Recirculating System (MARS) in patients with acute-on-chronic liver failure (ACLF) and an underlying alcoholic liver disease. In a case-control study, 13 patients treated with MARS were compared to 23 controls of similar age, sex and severity of disease. Inpatient hospital costs data were extracted from patients' files and hospital's internal costing. Patients and treating GPs were contacted, thus determining resource use and survival 1-year after treatment. Mean 1-year survival time in MARS group was 261 days and 148 days in controls. Kaplan-Meier analysis shows advantages of MARS patients (Logrank: P=0.057). Direct medical costs per patient for initial hospital stay and 1-year follow-up from a payer's perspective were Euro 18,792 for MARS patients and Euro 9638 for controls. The costs per life-year gained are Euro 29,719 (time horizon 1 year). From a societal perspective, the numbers are higher (costs per life-year gained: Euro 79,075), mainly because of the fact that there is no regular reimbursement of MARS and therefore intervention costs were not calculated from payer's perspective. A trade-off between medical benefit and higher costs has to be made, but 1-year results suggest an acceptable cost-effectiveness of MARS. Prolonging the time horizon and including indirect costs, which will be done in future research, would probably improve cost-effectiveness.

Adult↗