Time-domain control of ultrahigh-frequency nanomechanical systems.

Nanoelectromechanical systems could have applications in fields as diverse as ultrasensitive mass detection and mechanical computation, and can also be used to explore fundamental phenomena such as quantized heat conductance and quantum-limited displacement. Most nanomechanical studies to date have been performed in the frequency domain. However, applications in computation and information storage will require transient excitation and high-speed time-domain operation of nanomechanical systems. Here we show a time-resolved optical approach to the transduction of ultrahigh-frequency nanoelectromechanical systems, and demonstrate that coherent control of nanomechanical oscillation is possible through appropriate pulse programming. A series of cantilevers with resonant frequencies ranging from less than 10 MHz to over 1 GHz are characterized using the same pulse parameters.

Physical constraints and functional characteristics of transcription factor-DNA interaction.

We study theoretical "design principles" for transcription factor (TF)-DNA interaction in bacteria, focusing particularly on the statistical interaction of the TFs with the genomic background (i.e., the genome without the target sites). We introduce and motivate the concept of programmability, i.e., the ability to set the threshold concentration for TF binding over a wide range merely by mutating the binding sequence of a target site. This functional demand, together with physical constraints arising from the thermodynamics and kinetics of TF-DNA interaction, leads us to a narrow range of "optimal" interaction parameters. We find that this parameter set agrees well with experimental data for the interaction parameters of a few exemplary prokaryotic TFs, which indicates that TF-DNA interaction is indeed programmable. We suggest further experiments to test whether this is a general feature for a large class of TFs.

Validity of predicting mean arterial blood pressure during exercise.

PURPOSE: Mean arterial blood pressure (mean arterial pressure (MAP)) at rest is conventionally estimated as the product of the diastolic pressure plus one-third of the pulse pressure. Since pulse wave forms and the duration of diastole change during exercise, one might question the validity of this prediction equation for the exercise state. Our purpose was to test this by directly measuring blood pressure over a wide range of exercise intensities. METHODS: Pressure was recorded by arterial catheterization in 29 subjects performing progressive exercise and/or constant-load exercise at different intensities. Actual MAP was measured by integrating the area under the pulse curve and compared it with the value which was predicted from systolic and diastolic measures over heart rates ranging from 100 to 200 beats x min(-1). RESULTS: Predicted values were quite close to actual MAP, and the accuracy of the prediction equation changed minimally with increased exercise intensity. CONCLUSION: This method provides a valid estimation of MAP during exercise.

Hypotension following mild bouts of resistance exercise and submaximal dynamic exercise.

Our purposes were (1) to examine resting arterial blood pressure following an acute bout of resistance exercise and submaximal dynamic exercise, (2) to examine the effects of these exercises on the plasma concentrations of atrial natriuretic peptide ([ANP]), and (3) to evaluate the potential relationship between [ANP] and post-exercise blood pressure. Thirteen males [24.3+/-(2.4) years] performed 15 min of unilateral leg press exercise (65% of their one-repetition maximum) and, I week later, approximately 15 min of cycle ergometry (at 65% of their maximum oxygen consumption). Intra-arterial pressure was monitored during exercise and for 1 h post-exercise. Arterial blood was drawn at rest, during exercise and at intervals up to 60 min post-exercise for analysis of haematocrit and [alphaANP]. No differences occurred in blood pressure between trials, but significant decrements occurred following exercise in both trials. Systolic pressure was approximately 20 mmHg lower than before exercise after 10 min, and mean pressure was approximately 7 mmHg lower from 30 min onwards. Only slight (non-significant) elevations in [alphaANP] were detected immediately following exercise, with the concentrations declining to pre-exercise values by 5 min post-exercise. We conclude that post-exercise hypotension occurs following acute bouts of either resistance or submaximal dynamic exercise and, in this investigation, that this decreased blood pressure was not directly related to the release of alphaANP.

Randomised double-masked placebo-controlled trial of a treatment for congenital nystagmus.

Several therapies have been developed for congenital nystagmus (CN) but without placebo-controlled trials. We investigated a treatment which combined two therapies that had been advocated by several authors and were reported to improve visual acuity (VA). A placebo treatment was designed to mimic the time, attention, 'high tech' apparatus, and the explanation used in the experimental treatment. To each group, 38 subjects with CN were randomly allocated. Their VA and contrast sensitivity (CS) were assessed three times before undergoing treatment for 6 weeks and then once more. An improvement in VA occurred, however, this was not significantly different in the two groups. The improvement in CS was greater in the experimental than in the control group, but the difference failed to reach significance in most statistical tests. We conclude that putative therapies for CN should be assumed to be placebos until proven otherwise with randomized controlled trials.

Bilateral deficit in plantar flexion: relation to knee joint position, muscle activation, and reflex excitability.

Six male subjects made maximal isometric plantar flexions unilaterally (UL) and bilaterally (BL), with the knee joint angle positioned at 90 degrees and 0 degrees (full extension) and the ankle joint kept at 90 degrees. Plantar flexion torque and electromyogram (EMG) of the lateral gastrocnemius (LG) and the soleus (Sol) muscles were recorded. There was a deficit in torque in BL compared to UL (P<0.05), and the deficit was greater when the knee was extended than when bent to 90 degrees (13.9% vs 6.6%). The integrated EMG (iEMG) of UL and BL did not differ when the knee was at 90 degrees. On the other hand, when the knee was extended iEMG of LG was smaller for BL than for UL, suggesting that the larger bilateral deficit when the knee was extended was due to a reduced activity of the LG motor units. In addition, the H-reflex recorded from Sol when the contralateral leg was performing a maximal unilateral plantarflexion was reduced. This would indicate that the force deficit was associated with a reduction of motoneuron excitability.

Dynamically stabilized pores in bilayer membranes.

Zhelev and Needham have recently created large, quasistable pores in artificial lipid bilayer vesicles. Initially created by electroporation, the pores remain open for up to several seconds before quickly snapping shut. This result is surprising, in light of the large line tension for holes in bilayer membranes and the rapid time scale for closure of large pores. We show how pores can be dynamically stabilized via a new feedback mechanism. We also explain quantitatively the observed sudden pore closure as a tangent bifurcation. Finally, we show how Zhelev and Needham's experiment can be used to measure accurately the pore line tension, an important material parameter. For their stearoyloleoylphosphatidylcholine/cholesterol mixture we obtain a line tension of 2.6 x 10(-6) dyn.

Torsional directed walks, entropic elasticity, and DNA twist stiffness.

DNA and other biopolymers differ from classical polymers because of their torsional stiffness. This property changes the statistical character of their conformations under tension from a classical random walk to a problem we call the "torsional directed walk." Motivated by a recent experiment on single lambda-DNA molecules [Strick, T. R., Allemand, J.-F., Bensimon, D., Bensimon, A. & Croquette, V. (1996) Science 271, 1835-1837], we formulate the torsional directed walk problem and solve it analytically in the appropriate force regime. Our technique affords a direct physical determination of the microscopic twist stiffness C and twist-stretch coupling D relevant for DNA functionality. The theory quantitatively fits existing experimental data for relative extension as a function of overtwist over a wide range of applied force; fitting to the experimental data yields the numerical values C = 120 nm and D = 50 nm. Future experiments will refine these values. We also predict that the phenomenon of reduction of effective twist stiffness by bend fluctuations should be testable in future single-molecule experiments, and we give its analytic form.

The effects of variations in the anti-G straining maneuver on blood pressure at +Gz acceleration.

The increase in blood pressure provided by the standard AGSM is caused by both the contraction of the muscles of the lower body and by an increased intrathoracic pressure due to a respiratory straining (Valsalva) maneuver. This study examined the relative effectiveness and fatigability of the two components at +1 Gz and during +Gz acceleration in a human centrifuge. Brachial arterial pressure was recorded from a pressure-tip transducer in six subjects performing isometric leg presses only and on a separate occasion while performing respiratory straining only. Measurements were made over a range of intensities for the leg press contractions and Valsalva maneuvers and were conducted at +1 Gz and during slow and rapid onset runs up to +5 Gz in a human centrifuge. Blood pressure was also recorded during pulsing or intermittent contractions of the legs. We found it difficult to completely separate the blood pressure response to the leg press component from that of the respiratory straining alone component, since a moderate respiratory straining maneuver usually accompanied forceful contractions of the legs. We conclude, however, that a major portion of the elevation in blood pressure caused by the AGSM can be attributed to contraction of the muscles of the lower body and that this component is less fatiguing than the respiratory straining component. At +1 Gz a pulsing isometric contraction of the legs was no more effective in elevating blood pressure than a constant isometric contraction over the same duration.

Strength-velocity relationship and fatiguability of unilateral versus bilateral arm extension.

Strength-velocity relations and fatigue resistance in an arm bench press manoeuvre were compared between conditions of bilateral (BL, both arms acting together) and unilateral muscle contraction in 9 young men. BL and UL (sum of the 2 arms acting singly) strength was similar for isometric and slow isokinetic maximal voluntary contractions (MVC); at high velocities BL MVC declined more than UL. In both types of contractions a curvilinear relation was observed between strength and velocity, with significantly higher peak torques (PT) being produced under isometric conditions than for slow velocity efforts (p less than 0.01). Mean declines in PT during 100 repetitive MVCs of approximately 70s were to 25% of initial values for the BL fatigue test and to 37% for UL (p less than 0.01). In contrast to results of a similar investigation of leg extension in the same subjects, the arms showed no BL deficit of strength in the initial part of the strength-velocity curve and approximately twice as much fatigue in repetitive contractions. These physiological differences may stem from the varying habitual activity patterns of the arms and legs.

Arterial blood pressure response to heavy resistance exercise.

The purpose of this study was to record the blood pressure response to heavy weight-lifting exercise in five experienced body builders. Blood pressure was directly recorded by means of a capacitance transducer connected to a catheter in the brachial artery. Intrathoracic pressure with the Valsalva maneuver was recorded as mouth pressure by having the subject maintain an open glottis while expiring against a column of Hg during the lifts. Exercises included single-arm curls, overhead presses, and both double- and single-leg presses performed to failure at 80, 90, 95, and 100% of maximum. Systolic and diastolic blood pressures rose rapidly to extremely high values during the concentric contraction phase for each lift and declined with the eccentric contraction. The greatest peak pressures occurred during the double-leg press where the mean value for the group was 320/250 mmHg, with pressures in one subject exceeding 480/350 mmHg. Peak pressures with the single-arm curl exercise reached a mean group value of 255/190 mmHg when repetitions were continued to failure. Mouth pressures of 30-50 Torr during a single maximum lift, or as subjects approached failure with a submaximal weight, indicate that a portion of the observed increase in blood pressure was caused by a Valsalva maneuver. It was concluded that when healthy young subjects perform weight-lifting exercises the mechanical compression of blood vessels combines with a potent pressor response and a Valsalva response to produce extreme elevations in blood pressure. Pressures are extreme even when exercise is performed with a relatively small muscle mass.

Comparison of motor unit activation during unilateral and bilateral leg extension.

Possible differences between the extent of muscle utilization during leg extensions performed bilaterally (BL, both legs acting together) and unilaterally were investigated in young males in college. Significantly less integrated electromyographic activity was recorded from the quadriceps muscles of the dominant leg during BL compared with UL maximal voluntary contractions (MVC). BL strength was significantly lower than the summed (UL; sum of 2 legs acting singly) UL value under isometric conditions [BL = 91 +/- 2.5% (mean +/- SE) of UL; P less than 0.01, n = 9]. By use of a modified isokinetic dynamometer, it was also shown that the effect of increasing the velocity of concentric contraction was significantly greater (P less than 0.001) on BL than UL force development; thus at 424 degrees/s mean BL MVC was only 51 +/- 3.5% of UL. Greater resistance to fatigue was shown in the BL condition in repeated concentric contractions (% decline over 100 MVC at 105 degrees/s was 28 +/- 2.7% for BL vs. 38 +/- 2.9% for UL, P less than 0.001). Results indicated that the extent of motor unit activation appeared to be reduced in BL relative to UL MVC. Compatible evidence from the strength-velocity and fatigability comparisons suggested that this reduction was due to a lesser utilization of the fast-twitch fatigable type of motor unit.

Maximal aerobic capacity of Canadian schoolchildren: prediction based on age-related oxygen cost of running.

Timed distance runs were administered to a random sample of 2,683 schoolchildren aged 7--16 years. Oxygen uptake was then measured during level treadmill running over a range of submaximal speeds in a randomly selected subsample of 134 children with approximately equal representation according to age and sex. The VO2--running speed relationship was found to be related to age with the younger children having a greater VO2 per kg body weight than the older children when running at the same absolute speed. Based on the relationship found between measured VO2max and VO2max predicted according to field test performance, corrected for age-related differences in running efficiency, VO2max was predicted for all 2,683 children. When expressed per kg of body weight, VO2max was highest in girls at age 11 (approximately 44 ml/kg) and in boys at age 14 (approximately 54 ml/kg); however, differences among ages were nonsignificant. At all ages VO2max for the boys was significantly higher than that for the girls. At all ages, values were higher than those previously reported for Canadian schoolchildren.

[Intensive treatment of subarachnoid hemorrhage with objective worsening of patient status]. / Intensywne leczenie chorych po krwotoku podpajeczynówkowym przebiegajacym z pogorszeniem stanu przedmiotowego.

In the years 1971-1978 a group of 915 patients with subarachnoideal haemorrhage were treated at the Department of Neurosurgery, Medical Academy in Cracow. Surgical treatment was applied in 584 cases (63.82%). In 92 cases (10.05%) intensive treatment vas applied in view of deterioration in the course of the disease. The patients requiring intensive treatment were divided into 3 groups depending on the time of deterioration development (recurrence of subarachnoideal haemorrhage--27%, after angiography--11%, after surgical elimination of the aneruysm from the circulation--62%). The authors discuss the clinical symptoms and signs of deterioration, therapeutic management and nutrition. In the group with deterioration 76.08% of patients died, including 47.82% after operations. Deterioration was survived by 23.91%.

Effects of strength training and immobilization on human muscle fibres.

Seven healthy male subjects were studied under control conditions and following 5-6 months of heavy resistance training and 5-6 weeks of immobilization in elbow casts. Cross-sectional fibre areas and nuclei-to-fibre ratios were calculated from cryostat sections of needle biopsies taken from triceps brachii. Training resulted in a 98% increase in maximal elbow extension strength as measured by a Cybex dynamometer, while immobilization resulted in a 41% decrease in strength. Both fast twitch (FT) and slow twitch (ST) fibre areas increased significantly with training by 39% and 31%, respectively. Immobilization resulted in significant decreases in fibre area by 33% for FT and 25% for ST fibres. The observed nuclei-to-fibre ratio was 10% greater following the training programme. However, this change was non-significant. There was also a non-significant correlation between the magnitude of the changes in fibre size and the changes in maximal strength following either training or immobilization.

Mitochondrial volume density in human skeletal muscle following heavy resistance training.

Needle biopsies were taken from triceps brachii of 6 healthy males before and after a 6 month intensive weight training programme. The tissue was sectioned, photographed under a Philips EM200 and subjected to stereological analysis. Cross sectional fibre areas were also calculated from cryostat sections stained for ATPase activity. Morphometric analysis indicated that training resulted in a significant 26% reduction in mitochondrial volume density and a 25% reduction in the mitochondrial volume to myofibrillar volume ratio. These changes were accompanied by significant increases in fibre area for both FT (33%) and ST (27%) fibres as determined from the light microscope. There was a significant correlation between the reduction in mitochondrial volume density and the increase in FT fibre area following training (r=0.845). It was concluded that heavy resistance training leads to a dilution of the mitochondrial volume density through an increase in myofibrillar size with hypertrophy.

The energy cost of cross-country skiing among elite competitors.

The energy costs of skiing with the diagonal stride technique was investigated in 15 members of the men's and women's national cross-country ski teams and in 5 recreational skiers. Oxygen uptake was measured directly by means of a portable bag-method for each subject during level skiing at 3 different skiing speeds. The oxygen cost of double poling vs. diagonal stride techniques was also measured in 3 subjects during level skiing. Although a strong linear relationship was found between VO2 and speed of skiing (r = 0.868, p less than 0.001), there was considerable variation even among elite competitors. The VO2-skiing speed relationship was parallel to that obtained for running, but the O2 cost of skiing was found to be 10--12 ml/kg in excess of that predicted for level running at the same speed. On flat terrain, the O2 cost of the double poling technique as used in fast skiing was found to be higher than that for diagonal striding.