The physiological significance of p-Aminobenzoic Acid

Thesis submitted for the Degree of Doctor of Medicine in the University of the Witwatersrand, JohannesburgThe interest of the biochemist in para-aminobenzoic acid is very recent and, indeed, only goes back about five years, but in this time quite a voluminous literature has accumulated on the biological aspects and importance of this aniline derivative. Attention was originally focussed on it indirectly as a result of the intensive research devoted to the understanding of the mode of action of the various sulphonamides, which were shown during the last decade to be very powerful chemothera-peutic agents against many bacteria. Fildes (1940, propounded the hypothesis that p-aminobenzoic acid was an essential meta-bolite for bacteria, that it was normally associated with an enzyme system in the bacterial cell, and that sulphanilamide, being structurally similar to p-aminobenzoic acid, was capable in sufficient concentration of displacing p-aminobenzoic acid from its enzyme and stopping this essential line of metabolism. Fildes further suggested that a substance which was found to be an essential metabolite for bacteria would also be essential in the animal kingdom, so that such a substance might be found to act as a vitamin in the higher animals and even in man. In 19U1 interest in p-aminobenzoic acid was intensified with the announcement by Ansbacher (19U1J that p-eminobenzoic acid was actually a vitamin and should be included in the vita¬min B complex. In this thesis, studies on the absorption and excretion of p-aminobenzoic acid are reported, the estimation of p-amino- bensoic acid being based on its property of antagonising the Bulphonamides. Evidence is presented that p-arainobenzoic acid la excreted ae p-acetylaminobenzoic acid, and that its conjuga- tion with the acetyl radical probably takeB place in the liver. Further it is suggested that the experiments performed do not lend support to the view that p-aminobenzolc acid is a vitamin for man. Finally the various physiological effects of p-aminobenzoic acid are discussed and an attempt is made to gauge its function in the living organism. Preliminary experiments indicating a new, hitherto unreported, role of p-aminobenzoic acid are re¬corded, namely its ability in large doses to increase the re¬sistance of animals to disease.IT201

An examination of risk and resource sharing behavior between LTL trucking companies and warehouse providers

Increased demand for third-party logistics providers who can offer multiple services to their customers has encouraged many entities to explore innovative ways to expand service offerings. The current research examines Class I LTL motor carriers who have expanded their services to include warehousing. While there are several ways to achieve a service expansion into warehousing, the current research focuses on firms who have elected to expand by creating a strategic alliance type relationship with an external warehouse provider. The research examines carriers attitudes about risk and resource sharing in the alliance relationship. The results indicate that carriers are moderately receptive to sharing resources with their warehouse partner and relatively less interested in sharing risks with the warehouse partner

First principles numerical model of avalanche-induced arc discharges in electron-irradiated dielectrics

The model consists of four phases: single electron dynamics, single electron avalanche, negative streamer development, and tree formation. Numerical algorithms and computer code implementations are presented for the first three phases. An approach to developing a code description of fourth phase is discussed. Numerical results are presented for a crude material model of Teflon

Visual Acuity During Treadmill Walking

An awareness of the physical world is essential for successful navigation through the environment. Vision is the means by which this awareness is made possible for most people. However, without adequate compensation, the movements of the body during walking could impair vision. Previous research has shown how the eyes, head and trunk movements are coordinated to provide the compensation necessary for clear vision, but the overall effectiveness of these coordinated movements is unknown. The goal of the research presented here was to provide a direct measure of visual performance during locomotion, while also investigating the degree to which coordinated head and body movements can be altered to facilitate the goal of seeing clearly

Spaceflight-Induced Cardiovascular Changes and Recovery During NASA's Functional Task Test

Microgravity-induced physiological changes could impair a crewmember s performance upon return to a gravity environment. The Functional Task Test (FTT) is designed to correlate these physiological changes to performance in mission-critical tasks. The Recovery from Fall/Stand Test (RFST) simulates one such task, measuring the ability to recover from a prone position and the cardiovascular response to orthostasis. The purpose of this study was to evaluate spaceflight-induced cardiovascular changes during the FTT. METHODS: Five astronauts participated in the FTT before 10-15 day missions, on landing day (R+0), and one (R+1), six (R+6) and thirty (R+30) days after landing. The RFST consisted of a 2-minute prone rest followed by a 3-minute stand during which heart rate (HR, Holter) and continuous blood pressure (BP, Finometer) were measured. Spectral heart rate variability (HRV) was calculated during the RFST to approximate autonomic function. Statistical analysis was performed with two-factor repeated measures ANOVA. RESULTS: During RFST, HR was higher on R+0 than preflight (p<0.004). This increase in HR persisted on R+1 and R+6 during the stand portion of RFST (p<0.026). BP was well-regulated on all test days. Parasympathetic activity was diminished on R+0 (p=0.035). Sympathovagal balance tended to be affected by spaceflight (main effect, p=0.072), appearing to be slightly elevated during postflight RFST except on R+30. Additionally, analysis of HR during the functional tasks yielded a higher HR on R+0 than preflight during 8 of 11 tasks analyzed, where all tasks had HR return to preflight values by R+30 (p<0.05). CONCLUSION: Spaceflight causes an increase in HR, decrease in parasympathetic activity, and increase in sympathovagal balance, which we confirmed during RFST. These spaceflight-induced changes seen in the RFST, along with the increased postflight HR in most functional tasks, can be used to assess functional performance after short-duration spaceflight

Sex differences in functional limitations and the role of socioeconomic factors: a multi-cohort analysis

Background: Women are more likely to have functional limitations than are men, partly because of greater socioeconomic disadvantage. However, how sex differences vary by severity of functional limitations remains unclear. We examined sex differences in functional limitations, with attention to socioeconomic factors and severity of limitations. Methods: Longitudinal data on limitations in basic activities of daily living (ADL) and instrumental activities of daily living (IADL) and mobility activities were drawn from 62 375 participants from 14 countries. For ADL, IADL, and mobility, participants were categorised based on number of limited activities (0, 1, 2, or ≥3). Sex differences in limitations in four birth cohorts (1895–1929, 1930–38, 1939–45, and 1946–60) were analysed before and after adjustment for socioeconomic factors (education and labour force status). Findings: The prevalence of IADL and ADL limitations was higher in women than in men. After adjustment for socioeconomic factors, this sex difference was attenuated. The sex difference in IADL limitations at age 75 years (in the 1895–1929 cohort) was 3·7% before adjustment for socioeconomic factors (95% CI 2·6–4·7) and 1·7% (1·1–2·2) after adjustment. For ADL, the sex difference in limitations at age 75 years (in the 1895–1929 cohort) was 3·2% (2·3–4·1) before adjustment for socioeconomic factors and 1·4% (0·9–1·8) after adjustment. Sex differences in mobility limitations (16·1%, 95% CI 14·4–17·7) remained after adjustment for socioeconomic factors (14·3%, 12·7–15·9). After age 85 years, women were more likely to have three or more IADL or mobility limitations and men were more likely to have one or two limitations. Interpretation: Socioeconomic factors largely explain sex differences in IADL and ADL limitations but not mobility. Sex differences in mobility limitations in midlife are important targets for future research and interventions. Funding: National Institute on Aging, UK National Institute for Health Research, European Commission, and US Social Security Administration

Developing Personalized Sensorimotor Adaptability Countermeasures for Spaceflight

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. In this paper we will be presenting results from our ground-based study that show how behavioral, brain imaging and genomic data may be used to predict individual differences in sensorimotor adaptability to novel sensorimotor environments. This approach will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive capacity, brain structure, functional capacities, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes

Locomotor Dysfunction after Spaceflight: Characterization and Countermeasure Development

Astronauts returning from space flight show disturbances in locomotor control manifested by changes in various sub-systems including head-trunk coordination, dynamic visual acuity, lower limb muscle activation patterning and kinematics (Glasauer, et al., 1995; Bloomberg, et al., 1997; McDonald, et al., 1996; 1997; Layne, et al., 1997; 1998, 2001, 2004; Newman, et al., 1997; Bloomberg and Mulavara, 2003). These post flight changes in locomotor performance, due to neural adaptation to the microgravity conditions of space flight, affect the ability of crewmembers especially after a long duration mission to egress their vehicle and perform extravehicular activities soon after landing on Earth or following a landing on the surface of the Moon or Mars. At present, no operational training intervention is available pre- or in- flight to mitigate post flight locomotor disturbances. Our laboratory is currently developing a gait adaptability training program that is designed to facilitate recovery of locomotor function following a return to a gravitational environment. The training program exploits the ability of the sensorimotor system to generalize from exposure to multiple adaptive challenges during training so that the gait control system essentially "learns to learn" and therefore can reorganize more rapidly when faced with a novel adaptive challenge. Ultimately, the functional goal of an adaptive generalization countermeasure is not necessarily to immediately return movement patterns back to "normal". Rather the training regimen should facilitate the reorganization of available sensorimotor sub-systems to achieve safe and effective locomotion as soon as possible after space flight. We have previously confirmed that subjects participating in adaptive generalization training programs, using a variety of visuomotor distortions and different motor tasks from throwing to negotiating an obstacle course as the dependent measure, can learn to enhance their ability to adapt to a novel sensorimotor environment (Roller et al., 2001; Cohen et al. 2005). Importantly, this increased adaptability is retained even one month after completion of the training period. Our laboratory is currently developing adaptive generalization training procedures and the associated flight hardware to implement such a training program, using variations of visual flow, subject loading, and treadmill speed; during regular in-flight treadmill operations

A Hypothetical Perspective on the Relative Contributions of Strategic and Adaptive Control Mechanisms in Plastic Recalibration of Locomotor Heading Direction

We have previously shown that viewing simulated rotary self-motion during treadmill locomotion causes adaptive modification of the control of position and trajectory during over-ground locomotion, which functionally reflects adaptive changes in the sensorimotor integration of visual, vestibular, and proprioceptive cues (Mulavara et al., 2005). The objective of this study was to investigate how strategic changes in torso control during exposure to simulated rotary self-motion during treadmill walking influences adaptive modification of locomotor heading direction during over-ground stepping

Effect of Passive Horizontal Rotations and Vertical Oscillations on Dynamic Visual Acuity

Astronauts experience sensorimotor disturbances after long duration space flight. These crewmembers may need to egress the vehicle within a few minutes for safety and operational reasons in various sea state conditions following a water landing. Exposure to even low frequency motions induced by sea conditions surrounding a vessel can cause significant fine and gross motor control problems affecting critical functions. The objective of this study was to document human motor and visual performance during simulated wave motion in the 0.1 to 2.0 Hz range. We examined in 12 healthy subjects the changes in accuracy when performing a seated visual target acquisition task in which the location of target was offset vertically during horizontal full body rotation at an oscillating frequency of 0.8 Hz (peak velocity of 160 deg/s). The main finding was that the accuracy of performance degraded in 7 of 12 subjects when acquiring vertical targets at perturbing frequencies of 0.8 Hz in the horizontal plane by one step size. We also examined in a separate study on 12 healthy subjects seated dynamic visual acuity (DVA) task performance during vertical full body oscillations at perturbing frequencies of 2 Hz (peak to peak motion of 5 cm). The main finding was that DVA was significantly reduced when acquiring targets at perturbing oscillations at frequencies of 2 Hz in the vertical plane by approximately 1 chart line. Thus low frequencies of perturbations in the horizontal and vertical planes can cause decrement in visual performance