Space flight-induced bone loss has been attributed to a decrease in osteoblast function, without a significant change in bone resorption. To determine the effect of microgravity (MG) on bone, we used the Rotary Cell Culture System [developed by the National Aeronautics and Space Administration (NASA)] to model MG. Cultured mouse calvariae demonstrated a 3-fold decrease in alkaline phosphatase (ALP) activity and failed to mineralize after 7 d of MG. ALP and osteocalcin gene expression were also decreased. To determine the effects of MG on osteoblastogenesis, we cultured human mesenchymal stem cells (hMSC) on plastic microcarriers, and osteogenic differentiation was induced immediately before the initiation of modeled MG. A marked suppression of hMSC differentiation into osteoblasts was observed because the cells failed to express ALP, collagen 1, and osteonectin. The expression of runt-related transcription factor 2 was also inhibited. Interestingly, we found that peroxisome proliferator-activated receptor gamma (PPARgamma2), which is known to be important for adipocyte differentiation, adipsin, leptin, and glucose transporter-4 are highly expressed in response to MG. These changes were not corrected after 35 d of readaptation to normal gravity. In addition, MG decreased ERK- and increased p38-phosphorylation. These pathways are known to regulate the activity of runt-related transcription factor 2 and PPARgamma2, respectively. Taken together, our findings indicate that modeled MG inhibits the osteoblastic differentiation of hMSC and induces the development of an adipocytic lineage phenotype. This work will increase understanding and aid in the prevention of bone loss, not only in MG but also potentially in age-and disuse-related osteoporosis.

With the advances of power electronic technology, direct-driven permanent magnet synchronous generators (PMSGs) have increasingly drawn the interest of wind turbine manufacturers. At the present time, a commercial PMSG wind turbine primarily makes use of a passive rectifier followed by an insulated gate bipolar transistor (IGBT) inverter. Although a PMSG wind turbine with two back-to-back voltage source IGBT converters is considered more efficient, it has not been widely adopted by the wind power industry. This paper investigates both the conventional and a novel vector control mechanism for a PMSG wind turbine that has two side-by-side voltage source pulsewidth modulation converters. The proposed approach is based on a directcurrent vector control mechanism for control of both machineand grid-side converters of a PMSG wind turbine. Then, an optimal control strategy is developed for integrated control of PMSG maximum power extraction, reactive power, and grid voltage support controls. A transient system simulation using SimPowerSystem is built to investigate the performance of the conventional and proposed control techniques for the PMSG wind turbine under steady and gusty wind conditions. This paper shows that when using the direct-current vector control structure, a PMSG system has excellent performance in various aspects.Index Terms-DC-link voltage control, direct-current vector control, grid voltage support control, maximum wind power extraction, optimal control, permanent magnet synchronous generator (PMSG) wind turbine, reactive power control, voltage source converter (VSC).

Immunofluorescent techniques were used t o examine several aspects of B cell ontogeny in humans. Large lymphoid cells containing intracytoplasmic IgM (pre-B cells) were present in fetal liver as early as 7 weeks of gestation, approximately 2 weeks prior t o the appearance of surface IgM positive (sIgM+) B lymphocytes. Pre-B cells outnumbered sIgM+ B lymphocytes in fetal liver u p until the 13th week of gestation. In fetuses older than 13 weeks, pre-B cells and sIgM+ B lymphocytes were present in approximately equal proportions in liver and bone marrow. Pre-B cells in fetal liver, and fetal and adult marrow, were large and small (indicating a heterogeneous population of cytoplasmic IgM+. sIg-cells in these sites), while only the small pre-B cells were present i n fetal spleen, blood and lymph node. Lymphocytes bearing sIgG were detected earlier than those bearing sIgD o r sIgA, which were present by the 12th gestational week. Using double-staining techniques, we determined that during fetal life, (a) the proportion of B lymphocytes bearing only sIgM, as opposed t o those bearing both sIgM and sIgD, was much higher in liver and bone marrow than in spleen, blood and lymph node, and ( b ) sIgG, sIgA and sIgD appear independently on lymphocytes bearing sIgM. Studies of the frequency of doublestained cells for each combination of the four sIg isotypes indicated that B lymphocytes from neonatal humans may simultaneously bear three o r more sIg isotypes, whereas sIgG+ and sIgA+ B lymphocytes in adult blood usually express only the single isotype. Lower concentrations of anti+ antibodies were required for modulation of sIgM from B lymphocytes of fetal liver and adult bone marrow than for equivalent removal of sIgM from circulating B cells of mature individuals.In conjunction with data obtained in mice, our observations indicate that (a) the presence of large and small pre-B cells, (b) a high ratio of sIgM single t o sIgM.sIgD double B lymphocytes, and (c) increased sensitivity t o modulation of B cell sIgM by divalent anti-p antibodies define the fetal liver and adult bone marrow as bursa-equivalent sites in humans. Our results are consistent with a model o f isotype diversification in which immature sIgM+ cells give rise to B cell sublines devoted t o synthesis of each of the Ig classes, and sIgD is secondarily expressed on unstimulated B cells of all of these sublines.

2Spaceflight leads to reduced bone mineral density in weight bearing bones that is primarily attributed to a reduction in bone formation. We have previously demonstrated severely reduced osteoblastogenesis of human mesenchymal stem cells (hMSC) following seven days culture in modeled microgravity. One potential mechanism for reduced osteoblastic differentiation is disruption of type I collagen-integrin interactions and reduced integrin signaling. lntegrins are heterodimeric transmembrane receptors that bind extracellular matrix proteins and produce signals essential for proper cellular function, survival, and differentiation. Therefore, we investigated the effects of modeled microgravity on integrin expression and function in hMSC.We demonstrate that seven days of culture in modeled microgravity leads to reduced expression of the extracellular matrix protein, type I collagen (Col I). Conversely, modeled microgravity consistently increases Col I-specific a2 and PI integrin protein expression. Despite this increase in integrin subunit expression, autophosphorylatior! of adhesion-dependent kinases, focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 ( P Y U ) , is significantly reduced. Activation of Akt is unaffected by the reduction in FAK activation. However, reduced downstream signaling via the Ras-MAPK pathway is evidenced by a reduction in Ras and ERK activation. Taken together, our findings indicate that modeled microgravity decreases integrin/MAPK signaling, which likely contributes to the observed reduction in osteoblastogenesis. 3Altered human bone homeostasis during spaceflight results in severe decreases in bone mineral density, the severity of which directly correlates with flight duration [Bikle and Halloran, 19991. It has been estimated that 1-2% site-specific bone loss occurs in the human skeleton each month during spaceflight [Tilton et al., 19801. Investigations of the potential mechanisms underlying this phenomenon will provide insight into the causes of disuse and age-related osteoporosis. Several independent studies of humans during spaceflight have detected decreased serum levels of bone formation markers, including alkaline phosphatase, osteocalcin, and the C-terminal peptide of pro-collagen type I [Caillot-Augusseau et al., 2000; Collet et al., 19971. Previous in vitro studies of osteosarcoma cells in microgravity have also identified a reduction in markers of osteoblast function, including type I collagen, alkaline phosphatase, and osteocalcin gene expression [Carmeliet et al., 1998; Landis et al., 20001. Due to payload constraints, flight frequency, and cost, spaceflight experiments are limited. Therefore, NASA has developed a commercially available rotary cell culture system (RCCS) to model microgravity in ground-based experiments. We have previously used and described this system in detail [Zayzafoon et al., 20041. The high aspect ratio vessels (HARVs), used in the RCCS, provide two essential components of optimized suspension culture: 1) Solid body rotation an...