In-situ resource utilization technologies for Mars life support systems.

The atmosphere of Mars has many of the ingredients that can be used to support human exploration missions. It can be "mined" and processed to produce oxygen, buffer gas, and water, resulting in significant savings on mission costs. The use of local materials, called ISRU (for in-situ resource utilization), is clearly an essential strategy for a long-term human presence on Mars from the standpoints of self-sufficiency, safety, and cost. Currently a substantial effort is underway by NASA to develop technologies and designs of chemical plants to make propellants from the Martian atmosphere. Consumables for life support, such as oxygen and water, will probably benefit greatly from this ISRU technology development for propellant production. However, the buffer gas needed to dilute oxygen for breathing is not a product of a propellant production plant. The buffer gas needs on each human Mars mission will probably be in the order of metric tons, primarily due to losses during airlock activity. Buffer gas can be separated, compressed, and purified from the Mars atmosphere. This paper discusses the buffer gas needs for a human mission to Mars and consider architectures for the generation of buffer gas including an option that integrates it to the propellant production plant.

Adsorption processes in spacecraft environmental control and life support systems.

The environmental control and life support system on a spacecraft maintains a safe and comfortable environment in which the crew can live and work by supplying oxygen and water and by removing carbon dioxide, water vapor, and trace contaminants from cabin air. Although open-loop systems have been used successfully in the past for short-duration missions, the economics of current and future long-duration missions in space will make nearly complete recycling of air and water imperative. A variety of operations will be necessary to achieve the goal of nearly complete recycling. These include separation and reduction of carbon dioxide, removal of trace gas-phase contaminants, recovery and purification of humidity condensate, purification and polishing of wastewater streams, and others. Several of these can be performed totally or in part by adsorption processes. These processes are good candidates to perform separations and purifications in space due to their gravity independence, high reliability, relative high energy efficiency, design flexibility, technological maturity, and regenerative nature. For these reasons, adsorption has historically played a key role in life support on U.S. and Russian piloted spacecraft. Among the life support applications that can be achieved through use of adsorption technology are removal of trace contaminants and carbon dioxide from cabin air and recovery of potable water from waste streams. In each of these cases adsorption technology has been selected for use onboard the International Space Station. The requirements, science, and hardware for these applications are discussed. Human space exploration may eventually lead to construction of planetary habitats. These habitats may provide additional opportunities for use of adsorption processes, such as control of greenhouse gas composition, and may have different resources available to them, such as gases present in the planetary atmosphere. Separation and purification processes based on adsorption can be expected to continue to fulfill environmental control and life support needs on future missions.

Molecular analysis of C3 allotypes related to transplant outcome in human renal allografts.

The third component of complement (C3) exists in two main allotypic forms, C3S and C3F, which can be distinguished at the molecular level using a variation of the polymerase chain reaction. An increased frequency of the C3F allele has been noted in a number of autoimmune and inflammatory conditions affecting the kidney, including systemic vasculitis, IgA nephropathy, and type II mesangiocapillary nephritis. Recently, in an unrelated study, we found (with small numbers) an increased incidence of graft loss associated with the presence of the C3F allele. To further assess this, we analyzed the S/F polymorphism in 183 donor-recipient pairs of patients undergoing renal transplantation. Forty-one of 183 grafts were lost, but graft loss was not associated with the C3F allele over 14-month follow-up. However, the presence of the C3F allele predicted an increased risk of graft dysfunction (defined as serum creatinine > 150 mumol/L): 61/105 versus 36/78, with a relative risk of 1.4 (P < 0.05). The C3F allele predisposed toward graft dysfunction when present in either donor or recipient. The presence of two C3F alleles gave a relative risk for graft dysfunction of 1.8, suggesting a dose-dependent effect, although numbers were small. The presence of the C3F allele was not significantly correlated with the number of rejection episodes, serum creatinine, or duration of primary nonfunction. These findings suggest that C3F may be a susceptibility allele for allograft injury. Possible mechanisms for this association are discussed.

Expression and tissue localization of donor-specific complement C3 synthesized in human renal allografts.

Recent evidence suggests that the third component of complement, C3, is synthesized in renal tissue, and that increased C3 synthesis occurs in allograft rejection and immune complex-mediated nephritis. However, it is unclear whether intrinsic renal cells or migratory cells in the inflammatory infiltrate, possibly of recipient bone marrow origin, are the source of the C3 detected. This was investigated by determining the C3 allotypes of mRNA and protein produced by transplanted human kidney. Twenty donor-recipient pairs were examined, of which nine pairs had C3 allotypes that were informatively mismatched at the C3 F/S locus. Reverse transcriptase polymerase chain reaction (RT-PCR) followed by amplification refractory mutation system analysis showed intracellular donor-specific mRNA expression in six of these nine cases, at up to 61 days post-transplantation. Nested PCR reactions and the size of PCR products excluded contamination by genomic DNA. Allotype-specific staining of frozen sections of renal cortex demonstrated donor-derived C3 protein in both glomeruli and tubules of all biopsies examined, in a predominantly tubular distribution. These results imply that at least some of the pro-inflammatory effects of complement arise from intrinsic tissue synthesis of donor C3, and that this may represent a previously unrecognized source of tissue injury. The occurrence of local synthesis of C3 of donor allotype may have functional implications related to C3 allotype, and may also be relevant to strategies to inhibit intrarenal complement-mediated injury.

Molecular analysis of C3 allotypes in Chinese patients with immunoglobulin A nephropathy.

The third component of complement (C3) exists in two main allotypic forms, C3S and C3F. An increased frequency of the rarer C3F allele has been reported in several autoimmune conditions, including immunoglobulin A nephropathy (IgAN), in white patients. C3F is known to be rare in the Chinese population, but C3 allotypes have not been studied in Chinese patients with IgAN. The molecular basis of the S/F polymorphism has been established recently: a single base change at the DNA level encodes a single amino acid substitution in the protein. A second polymorphism, closely linked to the first, is defined by the monoclonal antibody HAV 4-1, and also is due to a single base change. These polymorphisms therefore can be analyzed at the DNA level. We have used the amplification refractory mutation system, a modification of the polymerase chain reaction, to analyze these two C3 polymorphisms on genomic DNA from 133 Hong Kong Chinese individuals: 54 patients with IgAN and 79 controls. No C3F alleles were present in either group: all individuals were homozygous C3S. Twenty-six patients were also allotyped for the HAV 4-1 polymorphism; all 26 were homozygous HAV 4-1 negative, as would be predicted from the close linkage of this allotype to C3S in other populations. These data indicate that C3F is not a susceptibility allele for IgAN in Hong Kong Chinese individuals, and confirm in a large DNA-based study the rarity of C3F in this population.

Molecular analysis of C3 allotypes in patients with systemic vasculitis.

The third component of complement (C3) exists in two main allotypic forms, C3S and C3F, distinguished at the DNA level by a single base change. An increased frequency of the rarer C3F allele has been reported in patients with the autoantibody nephritic factor and in several other autoimmune conditions such as rheumatoid arthritis and IgA nephropathy. Studies of the immunogenetic factors predisposing to the development of systemic vasculitis have produced conflicting results and no major genetic predisposing factors have been identified. We have studied the C3S/F polymorphism in 63 patients with systemic vasculitis using DNA allotyping by the amplification refractory mutation system, a modification of the polymerase chain reaction. The allele frequency in these patients was C3S 0.71, C3F 0.29 (expected C3S 0.8, C3F 0.19; chi-squared = 5.1, P < 0.025), with the average relative risk for the development of systemic vasculitis associated with the presence of a C3F allele being 2.6. Moreover, there was a marked excess of C3FF homozygotes (11/63, [17.5%], versus 4% expected: chi-squared = 9.5, p < 0.01). The average relative risk for the development of systemic vasculitis in C3F homozygotes was 5.1, indicating a gene dosage effect. These data indicate that the C3F allele is associated with a predisposition to the development of systemic vasculitis and that C3F homozygotes are at particularly high risk. This association is the strongest genetic factor reported so far for this group of diseases.

Molecular analysis of C3 allotypes in patients with nephritic factor.

The autoantibody nephritic factor (NeF) leads to complement consumption in vivo and is associated with type II mesangiocapillary glomerulonephritis (MCGN II) and partial lipodystrophy (PLD). The third component of complement (C3) exists in two common allotypic forms, C3S and C3F, distinguished at the protein level by electrophoresis. An increased frequency of the rarer C3F allele has been reported in several autoimmune conditions, including one small series of patients with NeF. However, patients with NeF have low levels of circulating C3 so that allotyping at the protein level is difficult. The molecular basis of the S/F polymorphism has recently been established: a single base change at the DNA level encodes a single amino acid substitution at the protein level. A second polymorphism, closely linked to the first, is defined by the MoAb HAV 4-1, and is also due to a single base change. These polymorphisms can therefore be analysed at the DNA level. We have used the amplification refractory mutation system (ARMS), a modification of the polymerase chain reaction (PCR), to analyse these two C3 polymorphisms at the DNA level in 26 patients with NeF. The allele frequencies of C3S and C3F were 0.673 and 0.327 (predicted values 0.79 and 0.2, chi 2 = 4.813, P < 0.05), giving a relative risk of 2.1 for the development of NeF conferred by the presence of a C3F allele. The HAV 4-1 allele frequencies were (-) 0.71 and (+) 0.29, i.e. not significantly different than predicted from the linked C3S/F allele frequencies. This is the largest series of patients with NeF yet published, and our data confirm an association between C3F and NeF. Possible mechanisms for for this link are discussed.