ALBERT

Description: Intravenous injections of the indirect sympathetic amine, tyramine, are used as a test of peripheral adrenergic function. The authors measured the time course of increases in ejection fraction, heart rate, systolic and diastolic pressure, popliteal artery flow, and greater saphenous vein diameter before and after an injection of 4.0 mg/m(2) body surface area of tyramine in normal human subjects. The tyramine caused moderate, significant increases in systolic pressure and significant decreases in total peripheral resistance. The earliest changes were a 30% increase in ejection fraction and a 16% increase in systolic pressure, followed by a 60% increase in popliteal artery flow and a later 11% increase in greater saphenous vein diameter. There were no changes in diastolic pressure or heart rate. These results suggest that pressor responses during tyramine injections are primarily due to an inotropic response that increases cardiac output and pressure and causes a reflex decrease in vascular resistance. Thus, tyramine pressor tests are a measure of cardiac, but not vascular, sympathetic function.

Description: An axial extensometer able to measure global bone strain magnitudes and rates encountered during physiological activity, and suitable for use in vivo in human subjects, is described. The extensometer uses paired capacitive sensors mounted to intraosseus pins and allows measurement of strain due to bending in the plane of the extensometer as well as uniaxial compression or tension. Data are presented for validation of the device against a surface-mounted strain gage in an acrylic specimen under dynamic four-point bending, with square wave and sinusoidal loading inputs up to 1500 mu epsilon and 20 Hz, representative of physiological strain magnitudes and frequencies. Pearson's correlation coefficient (r) between extensometer and strain gage ranged from 0.960 to 0.999. Mean differences between extensometer and strain gage ranged up to 15.3 mu epsilon. Errors in the extensometer output were directly proportional to the degree of bending that occurs in the specimen, however, these errors were predictable and less than 1 mu epsilon for the loading regime studied. The device is capable of tracking strain rates in excess of 90,000 mu epsilon/s.

Description: No abstract available

Description: Parathyroid hormone (PTH) is an 84-amino-acid polypeptide hormone functioning as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. PTH and PTH-related protein (PTHrP) indirectly activate osteoclasts resulting in increased bone resorption. During this process, PTH changes the phenotype of the osteoblast from a cell involved in bone formation to one directing bone resorption. In addition to these catabolic effects, PTH has been demonstrated to be an anabolic factor in skeletal tissue and in vitro. As a result, PTH has potential medical application to the treatment of osteoporosis, since intermittent administration of PTH stimulates bone formation. Activation of osteoblasts by PTH results in expression of genes important for the degradation of the extracellular matrix, production of growth factors, and stimulation and recruitment of osteoclasts. The ability of PTH to drive changes in gene expression is dependent upon activation of transcription factors such as the activator protein-1 family, RUNX2, and cAMP response element binding protein (CREB). Much of the regulation of these processes by PTH is protein kinase A (PKA)-dependent. However, while PKA is linked to many of the changes in gene expression directed by PTH, PKA activation has been shown to inhibit mitogen-activated protein kinase (MAPK) and proliferation of osteoblasts. It is now known that stimulation of MAPK and proliferation by PTH at low concentrations is protein kinase C (PKC)-dependent in both osteoblastic and kidney cells. Furthermore, PTH has been demonstrated to regulate components of the cell cycle. However, whether this regulation requires PKC and/or extracellular signal-regulated kinases or whether PTH is able to stimulate other components of the cell cycle is unknown. It is possible that stimulation of this signaling pathway by PTH mediates a unique pattern of gene expression resulting in proliferation in osteoblastic and kidney cells; however, specific examples of this are still unknown. This review will focus on what is known about PTH-mediated cell signaling, and discuss the established or putative PTH-regulated pattern of gene expression in osteoblastic cells following treatment with catabolic (high) or anabolic (low) concentrations of the hormone.

Description: Previously, we determined that the activator protein-1 (AP-1)-binding site and the runt domain (RD)-binding site and their binding proteins, c-Fos.c-Jun and Cbfa, regulate the collagenase-3 promoter in parathyroid hormone-treated and differentiating osteoblasts. Here we show that Cbfa1 and c-Fos.c-Jun appear to cooperatively bind the RD- and AP-1-binding sites and form ternary structures in vitro. Both in vitro and in vivo co-immunoprecipitation and yeast two-hybrid studies further demonstrate interaction between Cbfa1 with c-Fos and c-Jun in the absence of phosphorylation and without binding to DNA. Additionally, only the runt domain of Cbfa1 was required for interaction with c-Jun and c-Fos. In mammalian cells, overexpression of Cbfa1 enhanced c-Jun activation of AP-1-binding site promoter activity, demonstrating functional interaction. Finally, insertion of base pairs that disrupted the helical phasing between the AP-1- and RD-binding sites also inhibited collagenase-3 promoter activation. Thus, we provide direct evidence that Cbfa1 and c-Fos.c-Jun physically interact and cooperatively bind the AP-1- and RD-binding sites in the collagenase-3 promoter. Moreover, the AP-1- and RD-binding sites appear to be organized in a specific required helical arrangement that facilitates transcription factor interaction and enables promoter activation.

Description: NASA has concluded from previous studies that the twin engine tiltrotor is the most economical and technologically viable rotorcraft for near-term civil applications. Twin engine civil rotorcraft must be able to hover safely on one engine in an emergency. This emergency power requirement generally results in engines 20 to 50 percent larger than needed for normal engine operation, negatively impacting aircraft economics. This study identifies several contingency power enhancement concepts, and quantifies their potential to reduce aircraft operating costs. Many unique concepts were examined, and the selected concepts are simple, reliable, and have a high potential for near term realization. These engine concepts allow extremely high turbine temperatures during emergency operation by providing cooling to the power turbine and augmenting cooling of both turbines and structural hardware. Direct operating cost are reduced 3 to percent, which could yield a 30 to 80 percent increase in operating profits. The study consists of the definition of an aircraft economics model and a baseline engine, and an engine concept screening study, and a preliminary definition of the selected concepts. The selected concepts are evaluated against the baseline engine, and the critical technologies and development needs are identified, along with applications for this technology.

Description: OBJECTIVE: The objective of this study was to determine the effects of spaceflight duration on immune cells and their relationship to catecholamine levels. METHODS: Eleven astronauts who flew aboard five different US Space Shuttle flights ranging in duration from 4 to 16 days were studied before launch and after landing. RESULTS: Consistent with prior studies, spaceflight was associated with a significant increase in the number of circulating white blood cells (p 〈.01), including neutrophils (p 〈.01), monocytes (p 〈.05), CD3+CD4+ T-helper cells (p 〈.05), and CD19+ B cells (p 〈.01). In contrast, the number of CD3-CD16+56+ natural killer cells was decreased (p 〈.01). Plasma norepinephrine levels were increased at landing (p 〈.01) and were significantly correlated with the number of white blood cells (p 〈.01), neutrophils (p 〈.01), monocytes (p 〈.01), and B cells (p 〈.01). Astronauts who were in space for approximately 1 week showed a significantly larger increase on landing in plasma norepinephrine (p =.02) and epinephrine (p =.03) levels, as well as number of circulating CD3+CD4+ T-helper cells (p 〈.05) and CD3+CD8+ T-cytotoxic cells (p 〈.05) as compared with astronauts in space for approximately 2 weeks. CONCLUSIONS: The data suggest that the stress of spaceflight and landing may lead to a sympathetic nervous system-mediated redistribution of circulating leukocytes, an effect potentially attenuated after longer missions.

Description: A computational heat transfer methodology was developed to study the dual-engine linear aerospike plume induced base-heating environment during one power-pack out, in ascent flight. One power-pack out results in reduction of power levels for both engines. That, in turn, reduces the amount of base-bleed and changes the distribution of base-bleed on the two pillows. Hence, the concern of increased base-heating during power-pack out. The thermo-flowfield of the entire vehicle was computed. The computational methodology for the convective heating is based on a three-dimensional, finite-volume, viscous, chemically reacting, and pressure-based computational fluid dynamics formulation. The computational methodology for the radiative heating is based on a three-dimensional, finite-volume, and spectral-line-based weighted-sum-of-gray-gases absorption computational radiation heat transfer formulation. A separate radiation model was used for diagnostic purposes. The computational methodology was systematically benchmarked. In this study, near-base radiative heat fluxes were computed and they compared well with those measured from an installed linear aerospike engine tests. The base-heating environment of 18 trajectory points selected from three power-pack out ascent scenarios was computed and is presented here. The power-pack out condition has the most impact on convective base-heating when it happens early in flight. The some of its impact comes from the asymmetric and reduced base-bleed.

Description: Airport capacity is constrained, in part, by spacing requirements associated with the wake vortex hazard. NASA's Wake Vortex Avoidance Project has a goal to establish the feasibility of reducing this spacing while maintaining safety. Passive acoustic phased array sensors, if shown to have operational potential, may aid in this effort by detecting and tracking the vortices. During August/September 2003, NASA and the USDOT sponsored a wake acoustics test at the Denver International Airport. The central instrument of the test was a large microphone phased array. This paper describes the test in general terms and gives an overview of the array hardware. It outlines one of the analysis techniques that is being applied to the data and gives sample results. The technique is able to clearly resolve the wake vortices of landing aircraft and measure their separation, height, and sinking rate. These observations permit an indirect estimate of the vortex circulation. The array also provides visualization of the vortex evolution, including the Crow instability.

Description: Collagenase-3 mRNA is initially detectable when osteoblasts cease proliferation, increasing during differentiation and mineralization. We showed that this developmental expression is due to an increase in collagenase-3 gene transcription. Mutation of either the activator protein-1 or the runt domain binding site decreased collagenase-3 promoter activity, demonstrating that these sites are responsible for collagenase-3 gene transcription. The activator protein-1 and runt domain binding sites bind members of the activator protein-1 and core-binding factor family of transcription factors, respectively. We identified core-binding factor a1 binding to the runt domain binding site and JunD in addition to a Fos-related antigen binding to the activator protein-1 site. Overexpression of both c-Fos and c-Jun in osteoblasts or core-binding factor a1 increased collagenase-3 promoter activity. Furthermore, overexpression of c-Fos, c-Jun, and core-binding factor a1 synergistically increased collagenase-3 promoter activity. Mutation of either the activator protein-1 or the runt domain binding site resulted in the inability of c-Fos and c-Jun or core-binding factor a1 to increase collagenase-3 promoter activity, suggesting that there is cooperative interaction between the sites and the proteins. Overexpression of Fra-2 and JunD repressed core-binding factor a1-induced collagenase-3 promoter activity. Our results suggest that members of the activator protein-1 and core-binding factor families, binding to the activator protein-1 and runt domain binding sites are responsible for the developmental regulation of collagenase-3 gene expression in osteoblasts.