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At least 379 records · Page 21

Hemodynamics, renal function, plasma renin, and aldosterone in man after 5 to 14 days of bedrest

Continuous bedrest for 5 to 14 days had no significant effect on resting heart rate, blood pressure, or cardiac output in six normal men. Head-up tilt induced greater tachycardia in 5 of 6 patients after bed rest than in the control period. Propranolol diminished both tachycardia and the incidence of hypotension and faintness in upright posture. Plasma volume fell, extracellular fluid volume increased, and plasma renin activity was significantly elevated following bedrest. Unusually large increases in plasma renin followed head-up tilt or administration of isoproterenol during bedrest and after resuming normal activity. During bedrest, plasma aldosterone was often increased in the early morning. It is concluded that after bedrest, upright posture evokes strong beta-adrenergic activity as well as exaggerated metabolic and circulatory responses which can be reduced or abolished by the beta-adrenergic blocker, propranolol.

Melada, G. A.↗

Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans

Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.

Clinical Trial↗

Role of the calcium sensing receptor in cardiomyocyte apoptosis via mitochondrial dynamics in compensatory hypertrophied myocardium of spontaneously hypertensive rat

Calcium sensing receptor (CaSR) mediates pathological cardiac hypertrophy. Mitochondria maintain their function through fission and fusion and disruption of mitochondrial dynamic is linked to various cardiac diseases. This study examined how inhibition of CaSR by the inhibitor Calhex{sub 231} affected the mitochondrial dynamics in a hypertensive model in rats. Spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were used in this study. Cardiac function and blood pressure was evaluated at the end of the study. SHRs showed increases in the ratio of heart weight to body weight and the levels of CaSR; all of these increases were suppressed by Calhex{sub 231}. Additionally, Calhex{sub 231} treatment of SHRs changed the expression of proteins involved in mitochondrial dynamics. Our results demonstrated that CaSR activation induced cardiomyocyte apoptosis through the mitochondrial dynamics mediated apoptotic pathway in hypertensive hearts.

60 APPLIED LIFE SCIENCES↗

SU-F-T-187: Quantifying Normal Tissue Sparing with 4D Robust Optimization of Intensity Modulated Proton Therapy

Purpose: To report an approach to quantify the normal tissue sparing for 4D robustly-optimized versus PTV-optimized IMPT plans. Methods: We generated two sets of 90 DVHs from a patient’s 10-phase 4D CT set; one by conventional PTV-based optimization done in the Eclipse treatment planning system, and the other by an in-house robust optimization algorithm. The 90 DVHs were created for the following scenarios in each of the ten phases of the 4DCT: ± 5mm shift along x, y, z; ± 3.5% range uncertainty and a nominal scenario. A Matlab function written by Gay and Niemierko was modified to calculate EUD for each DVH for the following structures: esophagus, heart, ipsilateral lung and spinal cord. An F-test determined whether or not the variances of each structure’s DVHs were statistically different. Then a t-test determined if the average EUDs for each optimization algorithm were statistically significantly different. Results: T-test results showed each structure had a statistically significant difference in average EUD when comparing robust optimization versus PTV-based optimization. Under robust optimization all structures except the spinal cord received lower EUDs than PTV-based optimization. Using robust optimization the average EUDs decreased 1.45% for the esophagus, 1.54% for the heart and 5.45% for the ipsilateral lung. The average EUD to the spinal cord increased 24.86% but was still well below tolerance. Conclusion: This work has helped quantify a qualitative relationship noted earlier in our work: that robust optimization leads to plans with greater normal tissue sparing compared to PTV-based optimization. Except in the case of the spinal cord all structures received a lower EUD under robust optimization and these results are statistically significant. While the average EUD to the spinal cord increased to 25.06 Gy under robust optimization it is still well under the TD50 value of 66.5 Gy from Emami et al. Supported in part by the NCI U19 CA021239.

60 APPLIED LIFE SCIENCES↗

Amplitude distributions of the spider heartpulse in response to gravitational stimuli

The arachnid Nuctenea sclopetaria (Clerck) which possesses a neurogenic heart, measuring the heartbeat is under efferent control through a dorsal nerve arising from a brain center is discussed. It was shown that the heartrate of this spider is also modulated by an afferent input associated with small increments of gravity. A compressive force on the order of 40 micron is sufficient to elicit a threshold change in heart rate for a typical (100mg) spider. This obtains in a hyper-Gz field less than 1.001. The functional relationship between gravity and heartrate is logarithmic between the absolute threshold and at least 1.5 Gz. A model was proposed in which equilibrium and movement are maintained by changes in blood pressure. It is concluded that the arachnid equilibrium system is like a weight detector which employs a hydraulic compensatory mechanism.

Finck, A.↗

AGENDA: A task organizer and scheduler

AGENDA will be the main tool used in running the SPOT 4 Earth Observation Satellite's Operational Control Center. It will reduce the operator's work load and make the task easier. AGENDA sets up the work plan for a day of operations, automatically puts the day's tasks into sequence and monitors their progress in real time. Monitoring is centralized, and the tasks are run on different computers in the Center. Once informed of any problems, the operator can intervene at any time while an activity is taking place. To carry out the various functions, the operator has an advanced, efficient, ergonomic graphic interface based on X11 and OSF/MOTIF. Since AGENDA is the heart of the Center, it has to satisfy several constraints that have been taken into account during the various development phases. AGENDA is currently in its final development stages.

Fratter, Isabelle↗

The influence of central command on baroreflex resetting during exercise

The arterial baroreflex functions as a negative feedback system regulating blood pressure around an established operating point. Paradoxically, a parallel increase in heart rate and blood pressure manifests during exercise. Experimental evidence suggests these events are caused, in part, by a rapid resetting of the baroreflex by central command.

Non-NASA Center↗

Nature's Autonomous Oscillators

Nonlinearity is required to produce autonomous oscillations without external time dependent source, and an example is the pendulum clock. The escapement mechanism of the clock imparts an impulse for each swing direction, which keeps the pendulum oscillating at the resonance frequency. Among nature's observed autonomous oscillators, examples are the quasi-biennial oscillation and bimonthly oscillation of the Earth atmosphere, and the 22-year solar oscillation. The oscillations have been simulated in numerical models without external time dependent source, and in Section 2 we summarize the results. Specifically, we shall discuss the nonlinearities that are involved in generating the oscillations, and the processes that produce the periodicities. In biology, insects have flight muscles, which function autonomously with wing frequencies that far exceed the animals' neural capacity; Stretch-activation of muscle contraction is the mechanism that produces the high frequency oscillation of insect flight, discussed in Section 3. The same mechanism is also invoked to explain the functioning of the cardiac muscle. In Section 4, we present a tutorial review of the cardio-vascular system, heart anatomy, and muscle cell physiology, leading up to Starling's Law of the Heart, which supports our notion that the human heart is also a nonlinear oscillator. In Section 5, we offer a broad perspective of the tenuous links between the fluid dynamical oscillators and the human heart physiology.

Mayr, H. G.↗

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.

Clinical Trial↗

Transforming our understanding of chloroplast-associated genes through comprehensive characterization of protein localizations and protein-protein interactions

Bioenergy crops are a renewable source of fuels and are a critical base for building a carbon-neutral economy. Rational engineering of bioenergy crops has the potential to enhance the yields. However, our ability to engineer plants is limited because the functions of most genes remain unknown. Systematic characterization of gene function in plants thus has the potential to greatly accelerate bioenergy research. Here, we focus on the chloroplast, an underexplored energy-producing organelle that is a hallmark of plants. The chloroplast is one of the promising targets of biofuel crop engineering efforts because of its central role in photosynthesis, metabolism, and intracellular signaling. However, the protein composition of the chloroplast and the functions of most of its proteins remain poorly characterized. At the core of this project, we sought to comprehensively determine the localization of chloroplast-associated proteins and generate a spatially defined protein-protein interaction network for chloroplast. For this purpose, we used the leading model alga Chlamydomonas reinhardtii, which greatly increased experimental speed and throughput. We illustrated the value of our findings to land plants by determining the localization of Arabidopsis thaliana land plant homologs of the Chlamydomonas proteins. Altogether, we were successful in determining the localization of 1,034 chloroplast-associated proteins in Chlamydomonas. The localizations provide numerous insights into the spatial organization of chloroplasts and how they function to support photosynthesis. The localization patterns of distinct proteins revealed new chloroplast structures and revealed new spatial organization inside the chloroplast. We also identified new components of known chloroplast structures, such as the chloroplast envelope, nucleoid, plastoglobuli, and pyrenoid. We identified these new components by investigating the interacting partners of known proteins. Many proteins localized in both the chloroplast and other cellular structures, thereby hinting at new functions and communication between cellular structures. We also applied machine learning on the atlas to generate predictions for the location of all of the proteins in Chlamydomonas. This enabled us to assign putative functions to many uncharacterized proteins based on their cellular location. Altogether, this research establishes a rich resource that opens new avenues of investigation and guides future work in deciphering and manipulating chloroplast function. Next, we developed an extensive protein-protein interaction network for the chloroplast by performing affinity purification-mass spectrometry on ~1,150 tagged chloroplast-associated proteins, the first such large-scale study in any photosynthetic organism. This dataset reveals 4,694 high-confidence protein-protein interactions, offering insights into the functions of thousands of conserved poorly-characterized chloroplast proteins. This systematic identification of protein-protein interactions in the chloroplast also provides multiple exciting new research directions and a detailed blueprint of the chloroplast's operation. This research lays the groundwork to decipher the inner workings of the chloroplast, the cell structure at the heart of photosynthesis. The spatial atlas and protein-protein interactions reveal chloroplast organizational features that would not have been accessible with traditional approaches. The localization mapping, insights into the function, and research materials generated further provide a rich resource for the research community to advance the understanding of how the chloroplast is organized to enable engineering of enhanced photosynthetic organisms.

59 BASIC BIOLOGICAL SCIENCES↗

Correction to: The effect of beta blocker withdrawal on adenosine myocardial perfusion imaging

Regrettably the original version of the above article contained errors in Table 2 and wrong values in the text. The corrected table is presented here and the values which have been corrected now appear in bold text. Page 1223 abstract Global MBF showed an increase from 180.2 ± 59.9 to 193.6 ± 60.8 mL minute/100 g (P = .002) after beta blocker withdrawal. Page 1225 Mean systolic and mean diastolic blood pressure during adenosine were nearly identical (P = .77 and P = .79) with and without beta blocker. Mean heart rate and mean RPP during adenosine significantly increased after beta blocker withdrawal by 15.2% ± 17% (P = .001) and 16.2% ± 23% (P = .004), respectively. Page 1226 The data are listed in Table 2, lower third. Global MBF showed a significant increase by 7.4% ± 10% (P = .002) after beta blocker withdrawal. The individual data are depicted in Figure 1. All but three patients had a lower global MBF without beta blocker than with. The segmental MBF values (Figure 2) demonstrated a strong correlation over the entire range of perfusion values. The average effect was a slight perfusion shift of about 1015 mL minute-1/100 g in the range of 100-300 mL minute-1/100 g. The mCR under adenosine declined by 8.1% ± 11% (P = .038) and the normalized RPP by 16.2% ± 21% (P = .004) after betablocker discontinuation. Table 2 Hemodynamic response under adenosine, perfusion, and left-ventricular function.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Microvascular dysfunction in infiltrative cardiomyopathies

Infiltrative heart diseases are characterized by myocardial tissue alterations leading to mechanical dysfunction which in turn develops into bi-ventricular congestive heart failure. Also the coronary microvasculature undergoes significant remodeling and dysfunction. The effects of the unbalance of the mechanical cross-talk between cardiac muscle and vessels and of the impairment of vasodilatory function can be measured non-invasively by means of positron emission tomography and cardiac magnetic resonance.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Novel distribution of calreticulin to cardiomyocyte mitochondria and its increase in a rat model of dilated cardiomyopathy

Highlights: • Calreticulin can also be found in cardiomyocyte mitochondria. • The mitochondrial content of calreticulin is increased in DCM hearts. • Increased expression of mitochondrial CRT may induce mitochondrial damage. • Mitochondrial CRT may inhibit the phosphorylation of mitochondrial STAT3. - Abstract: Background: Calreticulin (CRT), a Ca{sup 2+}-binding chaperone of the endoplasmic reticulum, can also be found in several other locations including the cytosol, nucleus, secretory granules, the outer side of the plasma membrane, and the extracellular matrix. Whether CRT is localized at mitochondria of cardiomyocytes and whether such localization is affected under DCM are still unclear. Methods and results: The DCM model was generated in rats by the daily oral administration of furazolidone for thirty weeks. Echocardiographic and hemodynamic studies demonstrated enlarged left ventricular dimensions and reduced systolic and diastolic function in DCM rats. Immuno-electron microscopy and Western blot showed that CRT was present in cardiomyocyte mitochondria and the mitochondrial content of CRT was increased in DCM hearts (P < 0.05). Morphometric analysis showed notable myocardial apoptosis and mitochondrial swelling with fractured or dissolved cristae in the DCM hearts. Compared with the control group, the mitochondrial membrane potential level of the freshly isolated cardiac mitochondria and the enzyme activities of cytochrome c oxidase and succinate dehydrogenase in the model group were significantly decreased (P < 0.05), and the myocardial apoptosis index and the caspase activities of caspase-9 and caspase-3 were significantly increased (P < 0.05). Pearson linear correlation analysis showed that the mitochondrial content of CRT had negative correlations with the mitochondrial function, and a positive correlation with myocardial apoptosis index (P < 0.001). The protein expression level of cytochrome c and the phosphorylation activity of STAT3 in the mitochondrial fraction were significantly decreased in the model group compared with the control group (P < 0.05). Conclusions: These data demonstrate that CRT is localized at cardiomyocyte mitochondria and its mitochondrial content is increased in DCM hearts.

60 APPLIED LIFE SCIENCES↗

Functional Task Tests in Partial Gravity During Parabolic Flight

BACKGROUND Understanding how critical mission tasks are performed in partial gravity such as on the moon or Mars is necessary to define effective and comprehensive countermeasure strategies for preserving crew performance during exploration missions. We studied the performance of tasks such as standing, walking, and jumping during the partial gravity phases of parabolic flight. We hypothesized that the acute effects of partial gravity on vestibular, proprioceptive, and sensorimotor functions would negatively impact performance. METHODS Twelve subjects were tested over three flights of 30 parabolas each, including 10 parabolas at 0.25g, 10 parabolas at 0.5g, and 10 parabolas at 0.75g. Subjects also performed tests in 1g between parabolas. During the sit-to-stand with obstacle walk task, subjects rose from a seated position and walked as quickly as possible straight ahead towards a cone (4 m distance), walked around the cone making a 180° left turn, returned, and sat in the chair. On the way to and from the cone, subjects stepped over a 30 cm high obstacle. For the recovery from fall task, subjects lay prone for the pull-up phase and initial 10 sec of the parabola. Then they were asked to rise as quickly as possible and maintain a quiet stance for 10 sec. The tandem rail balance task involved standing with both feet on a 4.5 cm wide rail. The time ended when subjects either stepped off the rail or grabbed on to support straps. The jump down task started with the subjects standing on a 30 cm high platform, then the subjects were instructed to step off the platform, land with both feet simultaneously, and settle in a quiet stance. The cone of stability task involved subjects leaning about the ankles as far as they could in the anterior, posterior, and lateral directions without unfolding their arms or taking a step. The center of pressure distance between endpoints was calculated. Data were collected using inertial measurement units (Opal V2, APDM, Portland, OR) worn on the head and trunk, heart rate monitors (RS800CX, Polar, Kempele, Finland), and a force plate (Bertec, Columbus, OH). RESULTS Gravity level had a significant effect on performance, with the greatest changes from 1g tending to be at the 0.25g level (Table 1). Lower gravity levels were associated with increased times to complete the sit-to-stand obstacle walk task and the recovery from fall task, decreased change in heart rate during the recovery from fall task, decreased rail balance times, and increased cone of stability distance in the anterior-posterior direction. Table 1. Functional task performance at different gravity levels during parabolic flight. Measure0.25g0.5g0.75g1gp-valueSit-to-stand with obstacle walk time (sec)9.8 ±1.4*7.2 ±0.76.9 ±0.8*7.4 ±0.9<0.001Recovery from fall time to settle (sec)5.3 ± 0.9*4.6 ± 0.84.2 ± 0.64.3 ± 0.70.002Recovery from fall change in heart rate (bpm)6.0 ± 7.3*11.2 ± 6.5*14.9 ± 4.915.9 ± 6.5<0.001Rail balance with eyes open time (sec)2.7 ±0.8*4.8 ±2.16.6 ±4.78.4 ±6.70.031Rail balance with eyes closed time (sec)1.6 ±0.4*2.1 ±0.42.4 ±0.62.6 ±0.8<0.001Jump down time to settle (sec)2.1 ± 0.41.9 ± 0.42.0 ± 0.31.8 ± 0.30.328Cone of stability –anterior-posterior (cm)20.8 ±2.7*18.8 ±2.218.6 ±1.717.9 ±2.00.039Cone of stability –lateral (cm)26.8 ±6.624.4 ±2.123.0 ±2.123.8 ±2.30.215p-value: one-way repeated measures analysis of variance; *Significant pairwise difference from 1g (p<0.05). DISCUSSION These data suggest that there is a dose-response relationship between gravity level and functional task performance. The largest changes in performance were expected at the lowest gravity level (0.25g) because subjects would no longer be able to use the gravitational reference for the perception of upright. Understanding the extent of performance deficits informs the risks and design of countermeasures for exploration spaceflight missions. ACKNOWLEDGEMENT This work is supported by NASA’s Human Research Program Human Health Countermeasures Element.

T R Macaulay↗

Ion dynamics in an E × B Hall plasma accelerator

We show the time evolution of the ion velocity distribution function in a Hall plasma accelerator during a 20 kHz natural, quasi-periodic plasma oscillation. We apply a time-synchronized laser induced fluorescence technique at different locations along the channel midline, obtaining time- and spatially resolved ion velocity measurements. Strong velocity and density fluctuations and multiple ion populations are observed throughout the so-called “breathing mode” ionization instability, opening an experimental window into the detailed ion dynamics and physical processes at the heart of such devices.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Does Mckuer's Law Hold for Heart Rate Control via Biofeedback Display?

Some persons can control their pulse rate with the aid of a biofeedback display. If the biofeedback display is modified to show the error between a command pulse-rate and the measured rate, a compensatory (error correcting) heart rate tracking control loop can be created. The dynamic response characteristics of this control loop when subjected to step and quasi-random disturbances were measured. The control loop includes a beat-to-beat cardiotachmeter differenced with a forcing function from a quasi-random input generator; the resulting error pulse-rate is displayed as feedback. The subject acts to null the displayed pulse-rate error, thereby closing a compensatory control loop. McRuer's Law should hold for this case. A few subjects already skilled in voluntary pulse-rate control were tested for heart-rate control response. Control-law properties are derived, such as: crossover frequency, stability margins, and closed-loop bandwidth. These are evaluated for a range of forcing functions and for step as well as random disturbances.

Courter, B. J.↗

Analytical Models of Exoplanetary Atmospheres. IV. Improved Two-stream Radiative Transfer for the Treatment of Aerosols

We present a novel generalization of the two-stream method of radiative transfer, which allows for the accurate treatment of radiative transfer in the presence of strong infrared scattering by aerosols. We prove that this generalization involves only a simple modification of the coupling coefficients and transmission functions in the hemispheric two-stream method. This modification originates from allowing the ratio of the first Eddington coefficients to depart from unity. At the heart of the method is the fact that this ratio may be computed once and for all over the entire range of values of the single-scattering albedo and scattering asymmetry factor. We benchmark our improved two-stream method by calculating the fraction of flux reflected by a single atmospheric layer (the reflectivity) and comparing these calculations to those performed using a 32-stream discrete-ordinates method. We further compare our improved two-stream method to the two-stream source function (16 streams) and delta-Eddington methods, demonstrating that it is often more accurate at the order-of-magnitude level. Finally, we illustrate its accuracy using a toy model of the early Martian atmosphere hosting a cloud layer composed of carbon dioxide ice particles. The simplicity of implementation and accuracy of our improved two-stream method renders it suitable for implementation in three-dimensional general circulation models. In other words, our improved two-stream method has the ease of implementation of a standard two-stream method, but the accuracy of a 32-stream method.

79 ASTRONOMY AND ASTROPHYSICS↗