The International Society for Gravitational Physiology (ISGP) was established in 1991. It evolved from the prior International Union of Physiological Sciences (IUPS) Commission on Gravitational Physiology, established in 1973. The annual meeting in Gravitational Physiology was inaugurated by the Commission with a meeting, held jointly with the Fall Meeting of the American Physiological Society (APS), in 1979 in New Orleans, Louisiana USA. This was an exciting and well-attended meeting, which presaged our annual meetings thereafter. Further, with funding from NASA, the Proceedings of the meeting were published for the Commission by the American Physiological Society in a special supplement of their journal, The Physiologist.

From 1979 through 1993, the annual Gravitational Meeting was sponsored by the IUPS, frequently jointly with other societies. The meeting structure evolved to a four-day scientific meeting with four half-day morning symposia with invited speakers, on topics previously identified by the Commission, and four half-day sessions composed of voluntary papers. In addition, there was a separate day reserved for non-scientific interactions among the meeting registrants. This allowed for further interactions of the participants and a great deal of scientific and cultural exchange occured regularly during this time. The meeting location was also purposely rotated in order to meet with both scientists and students who may have had difficulty traveling internationally. The typical rotation included Western Europe, Eastern Europe, North America and Asia. In 1991, the Commission was instrumental in establishing an independent international society, the ISGP. Today our membership numbers approximately 1,000 individuals, representing over thirty countries. The ISGP is the sponsor of the Annual Gravitational Meeting, in concert with local host institutions and funding agencies. This meeting still utilizes the same five-day format and rotates location regularly. The ISGP Council of Trustees now manages the agenda and format of the meeting. In 1994, the ISGP also established the Journal of Gravitational Physiology, which, in addition to publishing peer-reviewed articles in the field, also publishes the annual meeting Proceedings.

Columbus, the European Space Agency orbital facility laboratory has been launched in February 2008 and attached to the International Space Station. In its launch configuration, Columbus includes 4 multi-user facilities: one of them is the European Physiology Modules Facility, also called EPM. The EPM is devoted to Human Physiology; later, it will be collocated in the Columbus module with two other physiology racks, i.e. the HRF-1 and HRF-2 American racks (Human Research Facility).

The EPM has been launched with two active scientific modules: - Cardiolab which includes 10 individual biomedical instruments (such as Cardiopres, blood pressure and ECG Holters, a portable Doppler, an air plethysmograph, a limb volume measurement device, one centrifuge for hematocrit determination, a blood chemical analyser and a haemoglobin analyser). - MEEMM (Multi Electrode Electroencephalogram Mapping Module) contains equipment to record EEG (up to 128 electrodes) and measure evoked potentials, a portable device for ambulatory measurements while astronauts are sleeping for example. The portable device is also able to measure muscle activity by measuring EMG signals.

The EPM also includes a sample collection kit which allows making blood, urine and saliva samples collection. The content of the kit being tuned to the scientific protocol that needs to collect biological samples.

CADMOS is part of the French Space Agency, located in Toulouse; it has been designated by the European Space Agency as the Facility Responsible Centre for the EPM. As a User Support and Operations Centre, CADMOS main goal is to help the scientists to perform their experiments in Space. Thus, the EPM related CADMOS main tasks are as follows: to participate in the experiment selection board and giving advice on whether experiments are feasible, to design and to have complementary equipment developed if necessary, to write the operational flight and ground procedures, to manage interfaces with the operational teams preparing missions and the scientific teams, to provide support for crew training, to deliver the experiment before the launch, to support the baseline data collection before and after the flight, to perform real-time monitoring and commanding during experiment operations, to store and archive experiment data and distributing data to PI

NASA's Human Research Program (HRP) is in the process of prioritizing biomedical research to be performed on the International Space Station (ISS). A subset of this research will require sample (blood, urine, saliva, etc.) return after retirement of the Space Shuttle in 2010. HRP is seeking to reduce sample return cost and minimize the risk associated with stowage by reducing the samples returned to Earth or by preserving samples in ways that reduce the need for conditioned stowage or by performing more in-flight analysis. The ISS Sample Return Analysis (ISRA) task assigned to Ames Research Center was conducted at the direction of HRP management. The task included a Measurement Survey to identify measurements needed by HRP and alternative analysis options, a Transportation Survey to examine methods available for delivering supplies to ISS and returning samples to Earth, a study of the implications of implementing specific strategies for solving the sample return problem, and an implementation strategy for two technologies, Flow Cytometry and Dried Chemistry. Results of these studies indicate that transportation is the biggest determinant of risk associated with return of samples, as is availability of adequate cold stowage. Timeliness and regularity of frozen sample return cannot be sustained without regular transportation beginning immediately after the retirement of Shuttle.

Reliance on MELFI or other freezers without adequate backup represents a significant risk; the lack of on-orbit refrigeration for samples or reagents could seriously impact the ability to obtain real-time data. Analysis of samples in-flight or storage at ambient temperature could help mitigate these risks, assuming that instrumentation provides the flexibility and capability required for HRP research. A combination of in-flight analysis, optimized storage capacity, and conversion of samples to ambient-tolerant formats will significantly reduce risks associated with capabilities not under HRP control. In this presentation we will focus on the latest work completed in the Technology Development portion of the ISRA and follow-on work including updated logistics projections, on-orbit analysis options, sample handling and existing capabilities will be presented. Current information on the on-going development of Flow Cytometry and Dried Chemistry by HRP, as well as other options, challenges and requirements for on-orbit analysis.

In order to alter the influence of gravity, different experimental and technical approaches have been developed. Depending on the experimental demands different clinostat devices have been constructed: a) a clinostat for the parallel operation and fixation of up to ten samples, b) submersed clinostats for research of aquatic systems, c) a clinostat microscope for direct observation during rotation. In addition, after specific labelling of the sample, a horizontal confocal microscope enables the in vivo analysis of cellular components during gravitropic or gravitactic responses. Correspondingly, various centrifuge devices - such as NIZEMI, the slow rotating centrifuge microscope - complete our experimental scenario. Experimental results on different cellular systems (protists, lymphocytes, plant systems) have demonstrated the efficiency of the applied tools as a prerequisite for space experiments with respect to the identification of gravisensitive processes and the specific preparation of experiments in real microgravity. Our group provides access to these facilities.

Recently a new centrifuge has been developed to serve the life and physical science community in conducting hypergravity experiments in a very versatile environment. The centrifuge, with a diameter of about 8 meters, has four arms. A total of 6 free swinging gondola can be accommodated on the arms. Each gondola has a capacity of 80 kg. payload that can be exposed to 20g. Each gondola is equipped with a series of utilities for the experiments. It provides a 220V power line, data communication for both monitor and commanding based on RS-232 serial connection, ethernet and USB protocols. Each gondola has a video camera and sensors for temperature and acceleration. Different gasses can be supplied to each gondola. The gondola can house various instruments such as furnaces or modules for combustion sciences, fluid or plasma physics studies. The facility is also outfitted for long duration animal studies for basic research and in preparation for space flight experiments. Each gondola is provided with water and air lines. The gondolas are draft and light tight. In addition, a central, on-axes, gondola is foreseen for rotation controls. The facility is fully programmable. Both, rotation profiles as well as experiment monitoring and commanding is performed via standard (LabView) programs. The facility will become available for ground based research in physical and life sciences but also technology / hardware related studies and tests starting from beginning 2008. The LDC centrifuge facility is located at ESA-ESTEC in Noordwijk, The Netherlands. (For J. van Loon this work is support through the NWO-ALW grant MG-057 via the Netherlands Institute for Space Research, SRON.)

Objective This study was aimed to investigate the expression of integrin subunits in osteoblasts during simulated microgravity induced by clinostat. Method Calvarial osteoblasts of neonate rats were cultured under conditions of normal gravity(1G) and simulated microgravity induced by clinostat respectively. The total RNA in cells was isolated in different time points (24, 48, 72 h). Reverse transcription PCR analysis was made to examine the gene expression of α₅, α_v and β₁ integrin subunits. Each value was normalized against that of β-actin mRNA. Moreover, the protein expressions of all kinds of integrin subunits were also detected with Western blotting.Results The gene expression of 3 integrin subunits started to change from 24 h of rotation in clinostat but not in stationary cultures. The expression of integrin α₅ mRNA decreased at 24, 48 and 72 h of rotation by 11.3%, 18.7% and 9.8%, respectively. The same trend was seen in the expression of integrin α_v mRNA as 23.0%, 12.3% and 16.7%, respectively. Moreover, the expression of integrin β₁ mRNA in different periods also declined by 15.3%, 11.4% and 26.4%, respectively. The differences were all statistically significant as compared with controls (P<0.05).The protein expression of 3 integrin subunits also started to change from 24 h of rotation in clinostat. The expression of integrin α₅ at 24, 48 and 72 h decreased by 13.1%, 20.3% and 11.9%, respectively. The same trend was seen in the expression of integrin α_v as 7.4%, 18.2% and 25.2%, respectively. Moreover, the expression of integrin β₁ protein in different periods also decreased by 18.6%, 25.9% and 27.5%, respectively. The differences were all statistically significant as compared with controls(P<0.05).Conclusion The expression of α₅, α_v, β₁ integrin subunits decrease in simulated microgravity. *Supported by National Natural Science Foundation of China (30300398, 30570456, 30600132, 30700141)

In the first part of gestation the human fetus develops under conditions similar to neutral floating and has an apparent weight which is about 5% of its actual weight. During the last 100 days of gestation the apparent body weight of the fetus is 70-80% of its actual weight. By the beginning of the third trimester the process of endochondral ossification has spread to all extremity bones and the vertebras, and at the time of delivery the total amount of calcium increases from the original 5g to 30g. Reduction of the mechanical stress caused by decreased apparent weight and muscle inactivity may significantly affect bone development and ossification during the last 100 days of gestation. Polyhydramnios increases the effects of buoyant forces on the fetus and decreases its apparent weight in the last trimester of gestation. Considering that in this period the specific weight of the fetus varies from 1200 kg/m³ to 1100 kg/m³, and of amniotic fluid from 1010 kg/m³ to 1020 kg/m³, polyhydramnios can reduce the apparent weight of the fetus to 10%-20% of its actual weight.

There is no data in the literature about the degree of bone formation and mineralization in newborns from these gestations. This paper presents a proposal for a study of bone development in gestations complicated by polyhydramnios. The inclusion criterion would be idiopathic polyhydramnios diagnosed by routine ultrasound examination. The apparent weights of fetuses would be determined by three-dimensional computer processing of the MRI images. After birth, the condition of bony tissue would be determined by evaluating bone mineral density and content using dual energy x-ray absortiometry (DXA) or alternatively ultrasound at various skeletal sites (femoral, tibial, radial and lumbar bones). Assessment of the bone turnover markers would provide further insights into the osteoblastic and osteoclastic processes. The degree of any deviation from the physiological bone development would be correlated with the degrees of polyhydramnios and fetal submergence in the amniotic fluid. On control examinations, performed at five years of age, any dynamics in the bony tissue would be recorded. Additionally, the critical period of fetal exposure to polyhydramnios after which the changes in bone development become irreversible would be defined. Studying the effects of hypogravity on prenatal bone development using the proposed model may have significant implications for future colonization of the solar system.

ε Basing on the analysis of available literature and the results of our own electron microscopic and radioautographic researches the data are presented about the morpho-functional peculiarities and succession of cellular interactions in adaptive remodeling of bone structures under normal conditions and after exposure of animals (rats, monkeys) to microgravity (SLS-2, Bion-11). The probable cellular mechanisms of the development of osteopenia and osteoporosis are considered. Our conception on remodeling proposes the following sequence in the development of cellular interactions after decrease of the mechanical loading: a primary response of osteocytes (mechanosensory cells) to the mechanical stimulus; osteocytic remodeling (osteolysis); transmission of the mechanical signals through a system of canals and processes to functionally active osteoblasts and surface osteocytes as well as to the bone-marrow stromal cells and to those lying on bone surfaces. As a response to the mechanical stimulus (microgravity) the system of stromal cell–preosteoblast–osteoblast shows a delay in proliferation, differentiation and specific functioning of the osteogenetic cells, some of the osteoblasts undergo apoptosis. Then the osteoclastic reaction occurs (attraction of monocytes and formation of osteoclasts and bone matrix resorption in the loci of apoptosis of osteoblasts and osteocytes). The macrophagal reaction is followed by osteoblastogenesis, which appears to be a rehabilitating process.

However, during prolonged absence of mechanical stimuli (microgravity, long-time immobilization) the adaptive activization of osteoblastogenesis doesn’t occur (as it is the case during the physiological remodeling of bone tissue) or it occurs to a smaller degree. The loading deficit leads to an adaptive differentiation of stromal cells to fibroblastic cells and adipocytes in these remodeling loci. These cell reactions are considered as adaptive-compensatory, but they don’t result in rehabilitation of the resorbed bone tissue. This sequence of events is considered as a mechanism of bone tissue loss which underlies the development of osteopenia and osteoporosis under the mechanical loading deficit.

Space flight results in bone loss due to decreased bone formation accompanied with unaltered or increased bone resorption. In addition, skeletal unloading leads to altered blood flow in bone and changes oxygen homeostasis in bone cells. These effects induce the expression of angiogenic factors, including vascular endothelial growth factor (VEGF), which affect bone remodeling. Placental growth factor (PlGF), a homolog of VEGF, not only amplifies the angiogenic response of VEGF in pathological conditions but exerts also pleiotropic effects on several cell types. We therefore investigated whether PlGF affected unloading-induced bone loss by analyzing the bone phenotype of PlGF^-/- and wild-type (WT) mice under basal conditions and after skeletal unloading by tail suspension.

PlGF^-/- mice were viable, fertile and did not display any developmental abnormalities. However, bone turnover was decreased in ageing PlGF-deficient mice compared to WT mice without a manifest effect on bone mass. Accordingly, serum osteocalcin levels and urinary excretion of collagen cross-links were reduced in the absence of PlGF. In vitro assays demonstrated that PlGF promoted osteoblast as well as osteoclast differentiation. Further studies elucidated that PlGF acted as an autocrine factor during osteoclastogenesis stimulating especially the later stages of osteoclast differentiation. These data suggest that PlGF functions as a positive regulator of bone remodeling by affecting both bone formation and bone resorption.

Unloading-induced bone loss is caused by unbalanced bone remodeling. Given PlGF's function in bone remodeling, we therefore questioned whether PlGF is involved in this process. Four weeks of skeletal unloading by tail suspension significantly reduced trabecular and cortical bone in WT mice, whereas only a moderate decrease was observed in PlGF^-/- mice. As expected in a condition of physical inactivity, dynamic bone formation parameters were drastically reduced in unloaded WT mice but not in PlGF^-/- mice compared to controls. Correspondingly, in vitro osteogenic differentiation of bone marrow stromal cells, isolated 2 weeks after tail suspension, was highly reduced in WT but not in PlGF^-/- cultures. In agreement, the reduction in serum osteocalcin levels, due to unloading, was more pronounced in WT mice compared to PlGF^-/- mice. Taken together, PlGF deficiency reduced unloading-induced bone loss.

In conclusion, deficiency of PlGF results in low bone turnover due to decreased osteoclast and osteoblast differentiation and hereby attenuates bone loss induced by skeletal unloading.

Introduction: We investigated the behavior of human chondrocytes exposed to simulated microgravity (μg) in vitro. The effects of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were evaluated. Materials and Methods: Human chondrocytes were cultured either on a tabletop random positioning machine (RPM) or under static 1g conditions. After 24 hours, cellular contents of apoptosis markers, growth factors and components of extracellular matrix proteins were determined.

Results: We could not detect activated caspase-3, nor enhanced production of p53, bax and bcl-2. VEGF and its receptor fetal liver kinase-1 (flk-1) were significantly elevated in chondrocytes, which had been cultured on the tabletop RPM. In addition, simulated μg induced enhanced amounts of chondroitin sulfate and aggrecan, no change in collagen type II and IV, but less quantities of collagen type I, X and of laminin, as compared with static 1g controls. The production of collagen type II/X, chondroitin sulfate and aggrecan was modified, when external bFGF or VEGF had been added to the cultures.

Morphology was changed by simulated microgravity. While the control chondrocytes (1g) grew as monolayers up to 18 days without changing their cytoskeletal structures, chondrocytes cultured under simulated μg conditions started to form elongated three-dimensional aggregates during the first five days. During further exposure to simulated microgravity, the aggregates thickened, incorporated collagens, secreted components of the cartilage and simultaneously rearranged their microtubules (alpha-tubulin) and intermediate filaments (vimentin).

Conclusions: Simulated microgravity using a tabletop RPM represents a new method for tissue engineering of cartilage.

Introduction: The prospect of sending a man to Mars is getting closer to reality, however long-term space travels induce physiological disorders. Bone loss is the major one because of its uncomplete recovery after come back on Earth. Our previous work suggested that vestibular deafferentation would participate in bone loss (BL) in male rats (Levasseur et al. J Vest Res 2004). Here we studied the long-term effect of bilateral vestibular deafferentation on BL in rat by measuring: 1) proportion and localization of BL, 2) sex related effect. The second objective was to test a pharmacological countermeasure (Risedronate, a recent bisphosphonate with low side-effects).

Method: Female and male groups were experimented respectively as followed: i) 5 pseudo-ovariectomized rats (Sh ovx) and 7 ovariectomized rats (Ovx) ± risedronate, 5 pseudo-bilabyrinthectomized rats (Sh bilab) and 7 bilabyrinthectomized rats (Bilab) ± risedronate; ii) 5 pseudo-orchidectomized rats (Sh orch) and 7 orchidectomized rats (Orch) ± risedronate, 5 pseudo-bilabyrinthectomized rats and 7 bilabyrinthectomized rats ± risedronate. BL was evaluated by tomography (Bone Mineral Density, g/cm²) for whole body (WB), spine at L3-L4 level (Spine), distal femoral metaphysis (DFM), femoral diaphysis (FD) and compared for each group at 0, 1 and 2 months. Serum bone alkaline phosphatase level (BAP; bone formation marker) and Cross-linked C-terminal telopeptides (CTX; bone resorption marker) was also measured at 0, 1 and 2 months. Bilabyrinthectomy was performed by bilateral injection of p-Arsanilic acid and vestibular dysfunction were confirmed using a clinical vestibular scale previously validated (Boadas-Vaello et al. Neurosci 2005), at 1 and 2 months.

Results: Diffuse (WB) and spine BL were significantly reported in Ovx group (-3.0%,-11% respectively), tended to decrease in Orch group, but remained unchanged in Bilab group at 1 and 2 months. BL of gonadectomized groups were over couterbalanced by Risedronate at 1 and 2 months for spine and WB. BL was regionally observed on DFM in Bilab and gonadectomized groups (-13.0% vs -24.0% in female and -11.9% vs -7.3% in male respectively) at 1 month. Risedronate over couterbalanced BL in gonadectomized and Bilab groups at 1 month. BL in Bilab male and female groups was not significantly observed at 2 months. BAP was significantly increased in female (+41.13%) and male (+24.70%) Bilab groups compared to Sh Bilab at 1 month. BAP was also increased in Ovx (+52.09%) compared to Sh ovx at 1 month. (BAP at 2 months and CTX levels are in progress).

Discussion: In our model of bilateral vestibular deafferentation, we showed that vestibular system induced transitory (1 month) regional BL on bearing bones compared to a model of diffuse osteoporosis (gonadectomized). The lack of regional BL at 2 months in Bilab groups suggests compensatory mechanisms requiring further investigations. Previous studies reported that vestibular system preferentially modulated vascular resistance of lower limb suggesting a regionalized organization of vestibular responses mediated by the autonomous nervous system. The mechanism of BL induced by the vestibular system is not known but could be mediated by the same way regarding the regional response of BL. Whatever the mechanism of BL-related vestibular system, bisphosphonate is an effective coutermeasure and which could be used in long-term space travels.

Traveling in space affects the whole human body. One of the most striking findings from prolonged space travel is the rapid bone loss because of lack of "loading forces", increasing risk of fracture and irreversible damage to the skeleton. To reproduce zero g environment in laboratory animals, localized disuse of the extremity has been induced in different ways (denervation [1], amputation [2], or devascularization [3]) leading to a permanent immobilization and inducing a rapid bone loss. However, it has been shown that this bone loss also results from a regional acceleratory phenomenon (RAP) caused by the surgical trauma [4]. At the present time, nonsurgical methods (immobilization by casting, bandaging or botulinium toxin type A injection [5-7]) have become more popular. Is the bone loss caused by a decrease in formation rates or by an increase in degradation rates? The aim of the present study was to elucidate the molecular events that occur in bone loss phenomenon due to localized disuse. Botox (BTX) injections have been used to induce the paralysis of the right hindlimb in the swiss mouse; saline injection in the left side was used as control. Left and right femur bone marrows were extracted at 0, 7, 14, 21 and 28 days after BTX injection and RNA were extracted to performed Q-PCR analyses. At the same time, the bone loss was assessed by microtomography on the tibias.

3D measurements showed a significant decrease of BV/TV (%)(control: 11.75 ±0.95; BTX: 8.5 ±0.67; p<0.05) and a significant increase of Tb/Pf (control:16.5 ± 1.9, BTX: 24.6 ±1; p<0.001) and of SMI (Control: 1.75 ± 0.08, BTX: 2.1 ± 0.02; p<0.001) from 7 days after BTX injection. Q-PCR revealed no modification in the expression of TGF-â and Runx2, implicated in non-Wnt ostegenesis pathway whereas differences were observed in genes involved in the Wnt pathway. Among them, the expression of LRP5 and LRP6 were significantly lower expressed from 7 days (LRP5 control: 224.7 ± 50.1, BTX:60 ± 15.2; p<0.001; LRP6 control:175.4±14.6, BTX: 98.2±22.3; p<0.001). From 14 days, Q-PCR revealed a significant increase of IL1-â expression (control: 53.9 ± 22.1, BTX:175.8 ± 49.2; p<0.01), an indicator of bone resorption. In conclusion, a zero g environnement, modelized by a localized disuse, induce modifications in the expression profile of bone microenvironnement leading to an rapid bone loss. Q-PCR showed an earlier decrease of Wnt pathway osteogenesis pursued by an late increase in bone resorption.

Objective: Pilots are usually suffered from cervical syndrome induced by their daily activities in the flight. The aim of this study is to explore the association of cervical syndrome£ CS£©in pilots with +Gz exposure by analyzing the effects of different sustained time of +Gz exposure on the intervertebral disc in rabbits.

Method: Twenty five rabbits from the laboratory animal center of FMMU were randomly divided into five groups: 1)control group, 2)£«6Gz/1 d group, 3)£«6Gz/2 wk group, 4)£«6Gz/4 wk group and 5)£«6Gz/6 wk group. The rabbits in group 2~5 were exposed to +6Gz/45s(5 times every day) for 1d, 2wks, 4wks and 6wks respectively. The rabbits in control group did not receive any +Gz exposure. Lateral Cervical Radiographies of each rabbit were performed with self-control method. Pathological changes of the cervical 3~7 vertebrae were observed by light microscope after staining with hematoxylin-eosin and picro-sirius. And the expression of BMP was examined with ABC immunohistochemical staining.

Results: As compared with control, the X-ray film revealed that there were no changes in the rabbits of 1 d and 2 wk group, while the changes such as intervertebral foramina shrink and intervertebral space obscure can be observed 4wk after +6Gz exposure. Besides the changes in the +6Gz/4wk group, articular surface sclerosis can be seen 6wk after +6Gz exposure. Histological results showed that irregular arrangement and some fissures occurred in fibrous ring of cervical intervertebral disc after 2 wk, 4 wk and 6wk after +6Gz exposure. Nucleus pulposus shrunken or became smaller in 4 wk and 6wk group and a few chondrocytes with BMP expression were diffusedly distributed in some specimens of annular fibrosus in rabbits of 6wk after +6Gz exposure. The collagen ¢ò migrated into the inner annular fibrosus gradually from the nucleus pulposus with the time of +Gz exposure.

Conclusion: This study confirmed that the degeneration of intervertebral disc can be promoted after repeated + 6 Gz exposures for 4wk or 6wk. This will facilited our understanding of mechanisms of +Gz exposure- induced CS and provide new protective measures.

The study of the relationship between the heart beat duration (QQ) and ventricular repolarization is important for the clinical evaluation of possible risks of acquired or congenital arrhythmias. While cardiac rhythm alterations were reported during previous space flights, no studies have been focused on the evaluation of T wave morphologic changes due to gravity (Gz), and their relationship with QQ. Our goal was to evaluate venticular repolarization during parabolic flight, in order to test the hypothesis that short-term exposure to microgravity induces alteration in ventricular repolarization. Methods. ECG recordings (Cardionics, 12 leads, 500 Hz) were obtained in 12 normal unmedicated male subjects (age 41±11 yrs) in upright position during twelve consecutive parabolas (Airbus A-300 Zero-G, Novespace, ESA-CNES, Bordeaux, France), with lower-body negative pressure (LBNP) at –50 mmHg activated at 0Gz in 4 randomly chosen parabolas.

Each heartbeat was classified according to the gravity level (Gz) at its time occurrence (1Gz, 1.8Gz, 0Gz, 1Gz recovery); then, for each Gz, a QQ duration histogram (10 msec bin amplitude) was calculated. For each bin, the corresponding beats were located on the ECG signal, and averaged to obtain a template representative of all the beats with that particular duration and Gz. For each averaged waveform, T-wave maximum amplitude (Tmax) was automatically extracted. Differences in Tmax among the gravity phases were tested (ANOVA, p<0.05). Results. At 0Gz, Tmax showed a significant increase (15%±4%) for each QQ, compared to 1Gz. With LBNP, the increase in Tmax at 0Gz was only 8% ±4%. At 1Gz recovery, Tmax was increased by 5%±2%, while no changes were found during 1.8Gz. Conclusion. Short-term exposure to microgravity during parabolic flight seems able to influence ventricular repolarization by increasing T wave amplitude. This fact could be related to: 1) augmented parasympathetic activation during 0Gz, that increases action potential dispersion in myocardial cells; 2) increased venous return, which causes cardiac dilation and increased conductibility in the thorax; 3) changes in heart position in respect of the electrodes. Further investigations are suggested to determine the effects of prolonged 0Gz exposure on ventricular repolarization.

To study the combined biological effects of cosmic radiation and microgravity on human cells, live biological samples of human fibroblasts were sent to space with the Foton-M3 mission on September, 14, 2007 from the Baikonur Cosmodrome in Kazakhstan with a Soyuz-U rocket launcher.

Cosmic rays contain heavy Z (mass) energy particles, also referred to as HZE. These particles are characterized by dense ionizations along the particles' travel paths (tracks). The Foton-M3 contained cell culture units that are designed for growing human cells on top of plastic track detectors. These plastic track detectors are specifically designed to colocalize HZE tracks with the expression of repair proteins for single and double strand DNA breaks in individual fibroblast nuclei after fluorescent immunostaining.

Fluorescently labelled gamma-H2AX and XRCC1 antibodies were used to measure synthesis and localization of proteins linked to DNA repair of double and single strand breaks, respectively. High Content Mosaic fluorescence recordings were made on a fully automated epifluorescence microscope, equipped with a sensitive EM-CCD camera. Prior to the flight mission, the general radiation sensitivity of the fibroblasts was measured by means of immunofluoresence and flow cytometry after exposure to increasing doses of X-rays. On average, cells in space were exposed to 4.28 ± 0.05 mGy compared to 0.35 ± 0.02 mGy in the ground controls. The HZE fluence rate was 1,5 tracks/cm²/day which equals a probability of all HZE impacts traversing a nucleus of around 8.4%. Preliminary results indicate that the general damage response expressed as mean fluorescence intensity of the fibroblasts is not influenced by global space conditions; however at the level of the single cell significant upregulation of DNA repair proteins was observed. Further analysis to quantify bystander effects in non-hit cells still has to be performed.

We know very little about the biological effects of long-term exposure to the various types and doses of radiation in space. We need a better understanding of these effects in order to protect travelers to the Moon and Mars. Because the wide range of radiation sources needed to reproduce space environments are not available on Earth, it is necessary to do space-based experiments. We are using the microscopic nematode Caenorhabditis elegans to increase our understanding of the effects of long-duration radiation exposure. The nematode is an excellent model organism for biological experiments due to its basic similarities to humans. C. elegans has a similar number of genes as humans (with approximately 60% that are orthologous) and uses conserved repair systems to protect against radiation induced DNA damage. In addition, each has neuromuscular systems and hormonal regulatory systems. C. elegans experiments have been to space on several missions ranging from a few days to a multi-generation trip spanning several months. Since the first NASA experiments in the early 1990's, to the 2004 collaborative ICE-First mission and most recently a six month NASA mission that returned to Earth June 22, 2007.

In these missions, four C. elegans mutagen testing systems have been used to analyze the effects of radiation: 1) poly-G/poly-C tract modifications; 2) assaying for dominant unc-22 mutations; 3) identifying alterations in telomere length; and 4) capturing and analyzing mutations using the eT1-system. The eT1 balancer samples approximately 1/6 of the entire genome and has been widely documented for mutagen testing. We have adapted the eT1-system into a "biological accumulating dosimeter" to be used to capture and analyze space radiation induced mutations. We are using NimbleGen micro-array chips to analyze the mutations from the ICE-First and subsequent six-month missions. Our results show it to be very effective for determining the molecular basis of captured deficiency and duplication mutations. In future, we will extend our analysis to Illumina Sequence Analyzer (a massively parallel sequencing instrument) to do whole genome resequencing of space derived genomes. In this way, we will be able to comprehensively look at the spectrum of changes following exposure to space radiation. These analyzes will help to inform the development of countermeasures necessary for protection on the ISS and long-duration manned space-flights to the Moon and Mars.

Space radiation has been long acknowledged as a potential showstopper for long duration manned interplanetary missions. Our knowledge of biological effects of cosmic radiation in deep space is almost exclusively derived from ground-based accelerator experiments with heavy ions in animal or in vitro models. In an effort to gain more information on space radiation risk and to develop countermeasures, NASA started several years ago a Space Radiation Health Program, which is currently supporting biological experiments performed at the Brookhaven National Laboratory (Upton, NY). Accelerator-based radiobiology research in the field of space radiation research is also under way in Russia and Japan.

Space radiation research in Europe has been mostly driven by flight experiments, and remarkable results were gathered in the field of space radiation dosimetry in low-Earth orbit. The European Space Agency (ESA) has recently established an ambitious exploration program (AURORA), and within this program it has been decided to start a ground-based space radiation biology program. Europe has a wide tradition in radiobiology research at accelerators, generally focussing on charged-particle cancer therapy. This expertise can be adapted to address the issue of space radiation risk.

To support research in this field in Europe, ESA issued in 2005 a call for tender for a preliminary study of investigations on biological effects of space radiation (IBER). The study group has recommended ESA to support a research program on biological effects of heavy ions using GSI in Darmstadt (Germany) as main facility. The new accelerator currently under construction at GSI, FAIR, will be able to provide beams at very high energy in the future, thus covering an energy range (2-20 GeV/n) of great importance in space but poorly explored so far. New biology research topics identified as possible targets for large integrated projects were noncancer later effects, acute effects by large solar particle events, and interaction of space radiation with other space environment stressors. An announcement of opportunity has been issued by ESA in March 2008, and this represent the first step toward a European Space Radiation Health Program.

In space, living organisms, including cells, are mainly affected by two new environmental conditions with regard to the Earth environment, namely: microgravity and high levels of radiations. Several experiments already demonstrated the influence of microgravity on "in vitro" mitogenic activation of T cells that were found remarkably depressed at low gravity. Here we assessed the effect of ionizing radiations on human blood cells by exposing cultured T lymphocytes from peripheral blood to the radiation environment previously measured inside the international space station (ISS). This ISS simulated radiation environment (available at SCKCEN) was obtained by applying similar ISS dose rates using a mixture of gamma (Cs-137) and neutron (Cf-252) sources.

In order to evaluate the effects of ionizing radiations on the T lymphocyte activation process, two kinds of experiments were conducted. A first kind of experiments mimicked a stratospheric balloon flight (SBF) in which T cells were irradiated for 24 hours in both non-activated and activated conditions by addition of Con A and anti-CD28.

In the second kind of experiments, we simulated a journey inside the ISS in which T lymphocytes were exposed to simulated radiations for either 30 min or 4 h after above activation. Concomitantly, T cells were also exposed to continuous radiation for 48h before activation.

Assuming that ionizing radiation causes direct and indirect cellular effects, partially by causing damage to the DNA structure or altering the signal transduction pathways that may consequently induce cell cycle arrest and apoptotic cell death, T cells were analyzed by flow cytometry for various parameters: cell size and granularity, caspase-3 activity, Bcl-2 regulation, cell counting, cell cycle and 8-oxo-2-guanosine staining (8-oxo-G).

In the simulated balloon experiment, we observed that activated cells were more sensitive to radiation than non-activated cells as shown by the decrease of cell numbers observed 24 hours after irradiation coupled with the increase of caspase-3 activity. However, Bcl-2 activity did not seem to be affected by the activation nor by the radiation. Furthermore, activation of cells induced an increase of the cell size and a parallel loss of cellular morphology. Cell cycle as well as 8-oxo-G were also modified upon radiation and activation and a final analysis is under progress. The experiments leading to better understanding the effects of cosmic radiation on board ISS, showed also a decrease in the cell number induced by the irradiation coupled with an important upregulation of Bcl-2. Caspase-3 was also shown to be more activated after irradiation.

In conclusion, we show that ISS like ionizing radiation environment induces a different response to activated and non-activated human T cells in terms of apoptosis. Gene expression studies are currently under progress in order to unravel the specific genes that are activated or repressed upon irradiation and activation. This will be discussed during this presentation. Research supported by Italian Space Agency (ASI)

Exposure of astronauts to space radiation, together with the reduced gravity level, represents the limiting factor for long duration space missions. There is increasing evidence that basic cellular functions are sensitive not only to radiation but also to microgravity. Previous space flight experiments have reported additive (neither sensitization nor protection) as well as synergistic (increased radiation effect under microgravity) interactions of radiation and microgravity in different cell systems. DNA repair studies in space on bacteria, yeast cells, and human fibroblasts, which were irradiated before flight, gave contradictory results: from inhibition of repair by microgravity to enhancement, whereas others did not detect any influence of microgravity on repair. The International Space Station (ISS) as the most important space-based research platform offers the possibility to perform relevant experiments. The space experiment CERASP (Cellular Responses to Radiation in Space) is scheduled to be performed using the BIOLAB facility onboard the COLUMBUS laboratory module. It is aimed to supply basic information on the cellular response in microgravity to radiation applied during flight and different biological end-points will be investigated after recovery of flown samples on ground.

CERASP makes use of recombinant human cell lines as reporters for cellular signal transduction modulation by genotoxic environmental conditions. The main biological endpoints under investigation will be gene activation based on green fluorescent protein (EGFP) expression controlled by DNA damage-dependent promoter elements which reflect the activity of the nuclear factor kappa B (NF-κB) pathway. NF-κB proteins comprise a family of structurally-related eukaryotic transcription factors that are involved in the control of a large number of cellular and systemic processes, such as immune and inflammatory responses, cellular growth, and apoptosis. In most normal cells, NF-κB is present as an inactive, IκB-bound complex in the cytoplasm. Activation by extracellular signals involves its release from the inhibitor protein IκBα and its nuclear translocation, where it acts as a transcriptional enhancer for target genes such as GADD45β, COX-2, Mn-SOD, Bcl-2, IL-6, and IκBα. Thereby it displays anti-apoptotic functions which lead to enhanced survival of affected cells in response to toxic stimuli. Results obtained with accelerated heavy ions (Ar, C) in ground-based studies (GANIL, Caen) show that high LET radiation activates NF-κB dependent on initial nuclear DNA damage followed by cytoplasmic signalling events. Expression of NF-κB dependent genes was followed after irradiation with sparsely and densely ionising radiation, using a qPCR approach. These results suggest a role of the NF-κB pathway as modulator of the radiation response. Therefore, regulation of this pathway may allow developing effective countermeasures for acute and late effects of radiation exposure during long-term space missions.

During long-term space travel astronauts are exposed to a complex mixture of different radiation types under conditions of dramatically reduced weight-bearing activity. Astronauts loose a considerable amount of bone mass at a rate up to one to two percent per month in space. Bone remodelling is a life-long process performed by balanced action of cells from the osteoblast and osteoclast lineages. Osteoblasts differentiate either into bone-lining cells or into osteocytes and play a crucial role in bone matrix synthesis. The balance between bone matrix assembly by osteocytes and bone degradation by osteoclasts may be modulated by microgravity as well as by ionizing radiation. Therapeutic doses of ionizing radiation cause bone damage and increase fracture risks after treatment for head-and-neck cancer and in pelvic irradiation. For low radiation doses, the possibility of a disturbed healing potential of bone was described. Cell lines with the potential to differentiate into bone-forming osteoblasts (OCT-1, MC3T3-E1 S24, and MC3T3-E1 S4) were used for studying radiation response after exposure to simulated components of cosmic radiation.

Cells were exposed to 150 kV X-rays, α-particles and accelerated heavy carbon or argon ions. Biological end-points under investigation were: cell survival (colony forming ability), cell cycle progression (FACS analysis of PI-stained DNA), and DNA damage (γH2AX-staining). Osteoblastogenesis was estimated by measurement of alkaline phosphatase (ALP) activity and production of mineralized matrix (von-Kossa staining). During osteoblastic cell differentiation, the expression of the bone specific marker genes osteocalcin (OCN) and osteopontin (OPN) was recorded (qRT-PCR). During differentiation induced by osteo-inductive media additives (50 µg/ml ascorbic acid, 10 mmol/l β-glycero phosphate) or by sparsely ionizing radiation (X-rays) OCN and OPN were highly expressed. After 21 days of post-irradiation incubation bone-like nodules were formed for OCT-1 and MC3T3-E1 S4 cells but nor for MC3T3-E1 S24 cells. A radiation-induced cell cycle arrest was resolved dose- and time dependently, accompanied by regulation of the cyclin kinase inhibitor CDKN1A (p21/WAF) and transforming growth factor beta 1 (TGF-β1). For exposure with high LET radiation (α-particles and accelerated C and Ar ions) a pronounced cell cycle block was evident. The results on the expression of differentiation markers OCN and Osterix (OSX) during radiation-induced premature differentiation of bone cells of the osteoblast lineage (OCT-1 cells) show that densely ionizing radiation results in expression of proteins essential for bone formation and consequently in an increase in bone volume. As radiation dependent permanent cell cycle blocks lead to a depletion of proliferation-competent cells from the osteoblastic precursor pool in the body, a gradual decrease of bone mass in weightlessness may be attributed to synergistic effects of radiation and weightlessness.

It is well documented that the cardiovascular system is influenced by weightlessness induced by spaceflight. It might be expected that the cardiovascular system adapts to six months of weightlessness during long-duration spaceflight in two phases: an early adjustment within the first weeks and a long-term acclimatization. However, data on cardiovascular adaptation during long-duration spaceflight are rare and conflicting.

Spaceflight induced changes in intravascular volume distribution and cardiovascular structure might affect autonomic cardiovascular control. Due to the similarity in blood volume redistribution, autonomic control during early spaceflight is expected to be similar to the autonomic control in supine position on earth. We hypothesized that during prolonged stay in space, autonomic cardiovascular control would adapt to changes in the cardiovascular system and total blood volume, reaching a new operating point which is no longer similar to preflight supine autonomic control.

Six male astronauts participated in this study of the evolution of autonomic cardiovascular modulation during 6 months of weightlessness during their stay on board of the ISS. ECG and continuous blood pressure were measured. Each subject performed the measurements 4 times during their space mission, on day 10, day 60, day 100 and day 160 after launch. Preflight reference measurements in supine and standing position were performed 30 days before launch. On day 10, heart rate was 64±6 bpm which is equal to heart rate in supine position before preflight (supine : 66±5 bpm; p=0.614). Also, results at day 10 in space did not differ from supine preflight values for mean arterial pressure (supine : 86±6 mmHg vs day10 = 85±6 mmHg ; p=0.848) and baroreflex sensitivity (supine : 11.3±2.2 ms/mmHg vs day10 = 13.3±3.4 ms/mmHg ; p=0.365). During six months of weightlessness, there was no significant evolution of heart rate (HR), mean arterial blood pressure (MAP) and baroreflex sensitivity (BRS) found using repeated measures ANOVA (HR : p=0.166 ; MAP : p=0.681 ; BRS : 0.697). It can be concluded that in space, autonomic cardiovascular control is similar to autonomic control in the supine position on earth. Autonomic cardiovascular control has already reached a stable operating point after 10 days of spaceflight and no further evolution during six months of weightlessness is seen.

Spaceflight induces changes in cardiovascular regulation. These can affect the astronaut’s ability to stand upright after return to earth. Previous studies of the impact of exposure to weightlessness during short-duration missions of 10 days in space have shown a altered cardiovascular autonomic respons to orthostatic stress. The first days after return, vagal modulation is decreased resulting in a sympathetic dominance.

In this study, the recovery of cardiovascular autonomic modulation after long-duration spaceflight (6 months) is evaluated over a period of 30 days. Six male astronauts who spent 6 months in space participated in the study. ECG and continuous blood pressure were measured for 10 minutes both in standing and supine position. The astronauts were asked to pace their breathing at 12 breaths per minute, guided by an audio stimulus with visual feed-back, in order to eliminate the possible influence of different breathing frequencies during different measurements. Measurements toke place 30 days before spaceflight (L-30) and on day 1 (R+1), day 5 (R+5), day 10 (R+10) and day 30 (R+30) after return from space.

None of the astronauts experienced difficulties to stand upright after landing. For each subject, postflight arterial blood pressure was comparable with preflight pressure and was maintained stable during standing indicating an adequate compensatory elevation in vascular resistance. First day after landing, in standing position, both low frequency and high frequency powers of RRI oscillations were depressed compared to preflight conditions (p<0.05). In supine position, only high frequency oscillations were depressed (p<0.05). In standing position, heart rate was significantly higher after return (103±14 bpm at R+1 ; 75±7 bpm at L-30 ; p<0.05) but restored quickly to preflight values (88±16 bpm at R+1 ; 75±7 bpm at L-30 ; p=NS). However, differences in heart rate and high frequency power of RRI oscillations were already recovered at R+5, postflight baroreflex sensitivity was decreased compared to preflight values until R+10 (5.9±1.6 ms/mmHg at L-30 ; 2.8±0.6 ms/mmHg at R+1 ; 3.5±1.2 ms/mmHg at R+5 ; 3.5±1.1 ms/mmHg at R+10 ; p<0.05 for each postflight measurement compared to L-30). It can be concluded that changes in cardiac autonomic control at day 1 after spaceflight are comparable between short-duration and long-duration spaceflight. While standing, vagal withdrawal and sympathetic dominance result in higher heart rates. Surprisingly, recovery of vagal control and heart rate after long duration spaceflight seems to be as fast as after short duration spaceflight (R+9). This may be the result of differences in exercise and countermeasures against cardiovascular deconditioning during the time spent on board of the spacecraft.

Microgravity is known to cause loss of bone and muscle mass. Current evidences indicate that impact loading, bone stress and muscular work, as implied by exercises such as treadmill running, are important countermeasures for maintaining bone and muscular mass. In microgravity, such an exercise requires a means to hold the subject down onto the surface of a treadmill while he/she runs. This report documents the current state of the second version of a prototype subject loading system, SLSv2, developed by the Université catholique de Louvain (UCL) and Arsalis (Belgium) in cooperation with the support of Verhaert Space (Belgium), the European Space Agency (ESA) and Prodex, specifically for the second generation treadmill (T2) on the International Space Station (ISS). Various designs have been theoretically assessed against the functional, size, mass and electrical power requirements set by the ISS International Partners. A pneumatic pressure design was retained. The pull-down force is applied via two cords attached to a harness worn by the subject and originating from two sub-surface exit pulleys located to either side of the running surface along its centerline. A test rack, including a motor that functions as a 'human', was built in order to assess the SLSv2 performance across its whole range of operation (pull-down force, displacement and step frequency) as well as its life cycle. The current SLSv2 can apply a total vertical pull-down force of 180 to 980 N to a subject running at a velocity of 2.4 to 20 km/h with a step frequency of <1.0 to 3.0 Hz. The SLSv2 attaches to the subject with a Technora cord (similar to Kevlar), allows vertical displacements of up to ±12.5 cm and accommodates a subject's fore-aft and medio-lateral displacement across the entire tread surface. The pull-down force remains within ±15 % of the average load for all loads, displacements and step frequencies, with a median value of ±8.2 %.

The current SLSv2 prototype meets or exceeds all functional requirements with one exception, the rate of change of load, which can easily be improved. The system was designed with an expected operational life of 10 years assuming a weekly usage of 16 hours. All bearings and bushings have an operational life exceeding requirements. It is expected that the piston seal and Technora cord will have to be replaced during routine annual maintenance. The actual life cycle and maintenance requirements of the SLS are still to be determined.

Respiratory Sinus Arrhythmia (RSA), usually the high frequency (HF) component of heart rate variability (HRV), is a cardiorespiratory interaction mediated by the vagus nerve. RSA is thus considered a marker of the parasympathetic modulation of heart rate. Previous studies reported decrease in RSA after spaceflight. Whether this can be due to autonomic adaption to microgravity or only result from a decreased blood volemia is still a matter of debate. The ESA Short-Arm Human Centrifuge (SAHC : outer radius = 2.82m, 2 tilting bed nacelles radially oriented + 2 chairs) was used to expose 6 male subjects to 3 different G-levels allong the head-to-feet axis (Gz). It is hypothesized that hyper-G can generate blood pooling in the legs that can mimic the post-spaceflight autonomic response as the one observed through the analysis of RSA during imposed and controlled breathing (ICB) protocols. Results from SAHC experiments are compared to results from similar ICB experiments performed before, during and after a short-duration (the 11 days odISSea) space mission.

When lying on the horizontally oriented bed, the heart was at ~1.05 m from the center. With rotations of 24, 29 and 32 rpm, Gz at heart level were 0.7, 1 and 1.2 g; and Gz at the head, and the feet, were 0.47, 0.66, 0.80 g and 1.5, 2.2, 2.6, respectively. For the 3 G-load, ECG, continuous blood pressure and respiration were recorded during 5 repetitions of a series of 3 ICB protocols. The breathing period (Tresp) was set at 6, 9 and 15 breaths per min (bpm) for at least 9 breaths. Per Gz level, test time lasted ~ 20 min. A dark environment canopy was placed over the head to ensure that the subjects had no cue of moving reference. Control measurements were obtained in standing and supine position. Similar ICB experiments were performed before, during, and after (days 1, 2, 4, 9, 15, 19 and 25 after landing) the 11 days odISSea mission on 3 male subjects. Tresp was set at 6, 7.5, 9, 12 and 15 bpm for 180s with the subject in supine and standing positions. The response of the Autonomic Nervous Systemto (ANS) to the orthostatic challenge (OC) was assessed by means of the use of a time domain algorithm, the "polar representation of the RSA". The slope of the regression of RSA amplitude and phase vs Tresp was used to assess the dynamic range of response.

Results on the SAHC show that the G-load lead to significant increased HR and decreased RSA amplitude at all Tresp. Results from the spaceflight experiments shows that early postflight HR was increased and RSA amplitude was decreased at all Tresp, and the slope of the regression of RSA amplitude with Tresp was decreased (all p<0.05).

The response of the ANS to the OC was thus evidenced by a sympathetic activation and/or parasympathetic withdrawal as well as a decreased dynamic range of response. Repetition of the protocol on the SAHC (duration of exposure to G-load) accentuates these differences, thus evidencing a cumulative effect with a very short time constant. The Gz-gradient seems to be an important factor of OC: even at a moderate 0.7 Gz at the heart, HR was significantly increased compared to supine and at 1.2 Gz this difference was even much more accentuated. This study demonstrate that blood pooling in the legs achieved by centrifugation has a a large influence on HRV and more particularly on RSA, and that this can partially reproduce the observed changes after a short-duration spaceflight.

The project MDS (Multifunctional Dynamometer for Application in Space) is an international collaboration of the University of Vienna (Department of Sport and Exercise Physiology), the Russian Academy of Sciences (Institute of Biomedical Problems) and the Technical University of Vienna (Institute for Engineering Design and Logistics Engineering) with the aim to develop a training and diagnostic device that counteracts the muscle and bone loss during long term space flights.

Due to the scientific results of the last years research in space medicine, it is well known, that the muscles and bones of the lower extremities and the trunk are most affected by the atrophy.

Based on this knowledge a various number of resistance exercises can be done in order to train the muscles of these parts of the body and to increase the efficiency of the training by intra- and intermuscular coordination (e.g. Squat, Bench Press, Dead Lift, Lat Pull, Calf Raise, Back Extension, Abdominal, Rowing exercise ...). All these exercises and a lot of variations of them can be done under ergonomic conditions, both by women and men with a body size from 150 cm to 190 cm (4,92ft to 6,23ft).

The resisting power for the training is provided by an electric motor, which is linked to a training-bar with two ropes. With the motor control the force, the position and the speed of the bar can be well-regulated for an isotonic, isometric and isokinetic training. These are requirements for the evaluation of the physical condition of the user.

An eccentric training mode is possible to provide higher stimulation of bones.

The daily training (isotonic) can be fulfilled with the load of 5 kg to 250 kg adjustable in steps of 5 kg via the user interface (touch screen). This is feasible by the torque control which allows the mode of operation as motor (eccentric) as well as generator (concentric).

In the 12-day flight of the Russian automatic spacecraft Foton-M3 (September 14-26, 2007) we performed a successful experiment with 12 Mongolian gerbils. Foton-M3 was not equipped with an air supply system. Due to this, we developed a self-contained Kontur module equipped with its own system of oxygen supply and removal of CO2 and other contaminants. Oxygen was delivered from a high pressure container through an electric valve turned on by the controlling gas analyzer. CO2 and other contaminants were scrubbed continuously by filter absorbents. The module developers had to meet stringent power consumption and mass requirements: the mass of the loaded module was 62 kg and total power consumption was 61 W/day.

The animals were housed in a cage of 125 x 255 x 370 mm (height x width x depth). The linear velocity of the constant top-to-bottom air flow was 0.3 m/s. The cage was made of 8 x 8 mm stainless steel mesh. The animals were provided with food bars made of natural products (cereals, dried fruit, supplements) and containing about 20% water. This moisture met gerbils’ requirements in water; therefore, the module was not equipped with a water supply system. Two 55 g food bars were provided once a day. Wastes were removed once a day using a special mechanism. The cage was equipped with yellow LEDs and the day/night cycle was 12:12 hours. The module was equipped with a digital video recorder located on the outside surface in front of a transparent window. In the module the environmental parameters were as follows: pO2 = 143-156 (mean 150) mm Hg, pCO2 - not more than 0.76 (mean 0.64) mm Hg, temperature = 23-28 (mean 26.7) 0C, and RH = 29% at the beginning and 57% at the end of flight (mean 39%). Throughout the entire flight video recording of the animals was performed continuously during the daytime. The authors express their gratitude to A. T. Logunov and S. A. Ivanov (Special Design Bureau at RF SRC IMBP RAS) who were responsible for the hardware and documentation development.

The project supported by the European Space Agency (ESA) in the frame of the "Microgravity Application Promotion Programme (MAP)" deals with the development and application of a new respiratory sensor system (RSS) for human respiratory investigations. Eight institutions, including three Industrial partners from different areas, combine their expertise by focusing on two selected applications in the field of ergospirometric exercise testing and lung function diagnostics with subsequent medication. The main goals of this project are to develop miniaturised oxygen and carbon dioxide sensors, to use their capability for simultaneous detection of total flow rates, to integrate them into a mask for the in-situ measurement of respiratory parameters, and to perform first qualification tests.

The key element for these investigations is the new miniaturised sensor system that enables a simultaneous in-situ measurement of O2, CO2 and volume/mass flow rates. This allows for direct in-situ measurements inside a mask during cardio-respiratory examinations of astronauts, athletes, and medical patients. Because of the in-situ measurement of the sensor inside the mask an adverse sample transport as necessary for other existing technologies can be avoided. Due to the very low response times of the sensor system, the possibility for a very accurate breath-by-breath analysis is also given.

For many manned space missions, and especially on the International Space Station, there is a need for a small, light-weight, portable, potentially body-mounted, metabolic gas analyser with which periodic fitness or scientific evaluations could be performed by the astronauts. The new system offers therefore a high flexibility for the astronauts, who will be able to conduct experiments at every location on-board the ISS while wearing a mask with an integrated sensor system and performing respiratory experiments in parallel. Furthermore, the sensor system shall be capable of being a stand-alone system providing real-time data display to permit evaluators to monitor data and archiving the metabolic data for post analysis.

The working principle of the developed gas sensors is based on the ion conductivity of ceramic materials. For ion conducting solid state electrolytes, e.g. yttria-doped zirconia, the conductivity starts at a temperature above 400°C. Therefore, the sensor is heated by an electrical resistance. Corresponding to the used sensor material and electrical circuits either a current or a voltage is measured that is directly dependent to the partial pressure of the specific gas.

The flow rate measurement profits from the high operating temperature gas sensors. By measuring the electrical power consumed to keep the sensor temperature constant, the original volume flow rate can be derived (similar to hot wire anemometry).

Project partners: TU Dresden - German Sport University Cologne - Karolinska Institutet, Stockholm - University Rostock - Univers. Libre de Bruxelles - Medisoft S.A. - ESCUBE GmbH

Severe storage limitations and low power requirements for spaceflight place an intense burden on the development of microminiaturized analytical technology for point-of-analysis use during space flight. Microfluidic devices can form the core of portable analytical systems having a minimal footprint and power consumption. The accurate manipulation of micro-, nano- and even picoliter volumes of sample and reagents within the nanospace of the microfluidic architecture allows for rapid analytical separations, both electrophoretic and chromatographic. In addition, because of fluidic interconnects with zero dead-volume, on-chip sample preparation can be carried out in a seamless manner.

The microfluidic chips and the accompanying instrumentation can be designed with sample-in/answer-out capabilities amenable to accepting real-world samples, execute multiple, sequential sample preparation steps, and then provide an interpretable read-out following separation and detection. With many of the chemistry challenges met for complicated integrated analysis, efforts are underway to minimize external hardware, simplify valving solutions for accurate fluidic control, and package into a portable system with improved detection sensitivity. The result - a bona fide micro-total analysis system – provides a technology ripe for translation to in-space flight analysis.

Spaceflight mediated changes in the physiology of biological systems is an intriguing area of research. Progress in this area has been limited, mainly due to lack of automated and easily transportable technologies that can be utilized for basic research in space. The space biologists' dream would be to have all the capabilities available on earth, based on current large scale laboratory instrumentation, but be automated, portable, and provide remote data access. With the advent of the Micro-Electro-Mechanical-Systems (MEMS) era, devices are now being developed which promise to fulfill the space biologists’ dream to enable next generation research capacities in spaceflight systems. By adopting a MEMS device approach, our lab is actively engaged in developing next generation Lab-on-a-chip (LOC) technologies for space biology research. We recently reported on the development and successful implementation of an in silico Cell Electrophysiology Lab-on-a-chip or CEL-C biochip. This biochip was developed for the basic science objective of understanding the role of asymmetric transcellular Ca²⁺ currents in gravisensing in Ceratopteris richardii fern spores. These currents play a key role in polarity development and subsequent growth of this single cell plant system. These currents were initially determined using the Self Referencing Ion Selective Electrode (SRIS) technology, which is based on large scale laboratory equipment, which prohibits microgravity and space flight experiments necessary to study this system. The CEL-C biochip which utilizes our specialized well-electrode technology enables measurement of transcellular Ca²⁺ currents, on 16 fern spores simultaneously, all on a biochip which is 9mm x 11mm.

The operation of the CEL-C biochip is completely automated after integration with our Bio HD-DAQ system. The technology was flown on a NASA C-9 parabolic flight and for the first time revealed detailed insight into the biophysical mechanisms of gravity perception in this system. Next generation technology is in development, including the CEL-C Advanced bioCD which will centrifugally simulate variable gravity for control and experimental treatments in microgravity environments. This technology will be integrated with microelectronics, motor and wireless telemetry and packaged in a <50kg GeneSat type microsatellite platform. The ImmunoSat platform is another biochip technology being developed in our lab which will focus on the understanding the effects of spaceflight environment on macrophage physiology. Called the 3N biochip, this technology combines a microfluidic cell culture platform with NO, nitrate and nitrite sensors and is aimed at understanding real time fluctuations in these key physiological parameters of macrophage immune response to the spaceflight environment. For biomedical monitoring, we are also developing the CCUP-ELISA biochip, an integrated platform for measuring Ca²⁺, creatine, urea, peroxide, NTx and CTx as key parameters of astronaut health in long duration missions. We expect that these technologies will become indispensable tools for ground and space based physiological research and will potentially lead to development of a generalized platform for biological research and medical diagnostics.

Since August 2006 several experiments have been performed in the European Modular Cultivation System (EMCS) on ISS. With a retrospect view this paper analyses the integration and operation of these past experiments and provides some lessons learned.

The paper aims to provide the research teams preparing experiments in the EMCS on ISS with an understanding of the key decision points in the integration and operations process.

All experiments have their unique science requirements and often the scientific strength of an experiment is anchored in the distinctive thoughts and approach each research team have to the research process.

With this in mind the integration and operation process has been tailored for each experiment to ensure that the recourses are used where they are needed the most.

The timeframe between each ISS crew rotations are named increments and the experiment integration is driven by the increment integration due-dates given by ESA and NASA.

Aspects that often cause questions difficult to answer by the research teams are related to the requirements for ground model testing and timing related to biological processes. Due to the unique nature of the EMCS and ISS environment it is often difficult to identify what type of tests will be required. The biological development stage are often used to determine when and experiment should be ended or move into a new phase while the increment planning is always based on the time between two activities.

It is expected that the conclusions of this paper will be instrumental for the future work of integration and experiment development teams as well as the science teams.