Orbital Payload Reductions Resulting from Booster and Trajectory Modifications for Recovery of a Large Rocket Booster

An analysis was made to determine the reduction in payload for a 300 nautical mile orbit resulting from the addition of inert weight, representing recovery gear, to the first-stage booster of a three-stage rocket vehicle. The values of added inert weight investigated ranged from 0 to 18 percent of gross weight at lift off. The study also included the effects on the payload in orbit and the distance from the launch site at burnout and at impact caused by variation in the vertical rise time before the programmed tilt. The vertical rise times investigated ranged from 16-7 to 100 percent of booster burning time. For a vertical rise of 16.7 percent of booster burning time it was found that a 50-percent increase in the weight of the empty booster resulted in only a 10-percent reduction of the payload in orbit. For no added booster weight, increasing vertical rise time from 16-7 to 100 percent of booster burning time (so that the spent booster would impact in the launch area) reduced the payload by 37 percent. Increasing the vertical rise time from 16-7 to 50 percent of booster burning time resulted in about a 15-percent reduction in the impact distance, and for vertical rise times greater than 50-percent the impact distance decreased rapidly

Lift, Drag, and Pitching Moments of an Arrow Wing Having 80 Degree of Sweepback at Mach Numbers from 2.48 to 3.51 and Reynolds Numbers up to 11.0 Million

Measurements were made of the lift, drag, and pitching moments on an arrow wing (taper ratio of zero) having an aspect ratio of 1.4 and a leading-edge sweepback of 80 (degrees). The wing was designed to have a subsonic leading-edge and a Clark-Y airfoil with a thickness ratio of 12 percent of the chord perpendicular to the wing leading edge. The wing was tested both with and without the wing tips bent upward in an attempt to alleviate possible flow separation in the vicinity of the wing tips. Small jets of air were used to fix transition near the wing leading edge. Force results are presented for Mach numbers of 2.48, 2.75, 3.04, 3.28, and 3.51 at Reynolds numbers of 3.5 and 9.0 million and for a Mach number of 3.04 at a Reynolds number of 11.0 million. The measured aerodynamic characteristics are compared with those estimated by linear theory. The maximum lift-drag ratio measured was much less than that predicted. This difference is attributed to lack of full leading-edge thrust and to the experimental lift-curve slope being about 20 percent below the theoretical value

Brief Embryonic Strychnine Exposure in Zebrafish Causes Long-Term Adult Behavioral Impairment with Indications of Embyronic Synaptic Changes

Zebrafish provide a powerful model of the impacts of embryonic toxicant exposure on neural development that may result in long-term behavioral dysfunction. In this study, zebrafish embryos were treated with 1.5mM strychnine for short embryonic time windows to induce transient changes in inhibitory neural signaling, and were subsequently raised in untreated water until adulthood. PCR analysis showed indications that strychnine exposure altered expression of some genes related to glycinergic, GABAergic and glutamatergic neuronal synapses during embryonic development. In adulthood, treated fish showed significant changes in swimming speed and tank diving behavior compared to controls. Taken together, these data show that a short embryonic exposure to a neurotoxicant can alter development of neural synapses and lead to changes in adult behavior

Reliability and Feasibility of the Four Square Step Test for Use in Children with Cerebral Palsy: A Pilot Study

Purpose: The ability to maintain standing balance with a moving base of support and while making rapid postural adjustments is important for independence in various functional activities. Clinical tests and measures have not addressed this ability in children with disability. This pilot study examined the feasibility and reliability of the Four Square Step Test (FSST) as a test of dynamic balance in children with cerebral palsy (CP). Method: Four children with CP (Gross Motor Function Classification Scale levels I-II) were tested on the FSST by 3 assessors on the first occasion (interrater reliability) and repeat-tested by 1 assessor after 2 weeks (test-retest reliability). Six children with typical development (TD) were tested on a separate occasion to explore any between-group difference in performance. Results: The FSST was easy to setup, required no specialized equipment, could be completed in 5 minutes, and might be carried out by clinicians with limited experience in pediatric therapy. It demonstrated excellent interrater reliability (ICC = 0.832) and test-retest reliability (ICC = 0.979) in children with CP. Compared with FSST times for children with TD (mean = 9.12 ± 2.67 seconds), times for children with CP (mean = 18.38 ± 9.02 seconds) were significantly slower (p = 0.019, Mann-Whitney U = -2.345). Conclusions and Recommendations: The pilot study provides initial evidence on the potential usefulness of the FSST as a test of dynamic standing balance in children with CP. This warrants further investigation of the clinimetric properties of the FSST using an adequate sample size

Different Lines of Rats Selectively-Bred for High Alcohol-Drinking Demonstrate Disparate Preferences for Nicotine Self-administration

Background. Alcohol and nicotine are commonly co-abused. The search for a common core of neural, behavioral, and genetic factors underlying addiction has been the goal of addiction research. Purpose. Genetic predisposition to high alcohol intake has been studied in rats by selectively breeding rats that have high preference for alcohol. The current experiments were conducted to determine if the level of intravenous nicotine administration for the various lines of alcohol-preferring rats differs from that for nonalcohol-preferring controls. Study design. Adult alcohol-naïve selectively-bred alcohol-preferring male rats from four lines (P, AA, HAD-1, sP) and their control nonalcohol-preferring rats (NP, ANA, LAD-1, sNP) were trained and given access to self-administer nicotine (0.03 mg/kg/infusion). Results. The results show that the P rats self-administered significantly more nicotine than NP rats. In contrast, there were no significant differences in nicotine self-administration between the sP and sNP or the AA and ANA rats. Unexpectedly, high alcohol-drinking HAD-1 rats self-administered significantly less nicotine than low alcohol-drinking LAD-1 rats. Conclusion. This suggests that some genetic factors that underlie high-alcohol intake have more general effects in promoting high nicotine intake tendencies, while other genetic factors are more specific to only heavy drinking

Developmental Exposure of Rats to Chlorpyrifos Leads to Behavioral Alterations in Adulthood, Involving Serotonergic Mechanisms and Resembling Animal Models of Depression

Developmental exposure to chlorpyrifos (CPF) causes persistent changes in serotonergic (5HT) systems. We administered 1 mg/kg/day CPF to rats on postnatal days 1–4, a regimen below the threshold for systemic toxicity. When tested in adulthood, CPF-exposed animals showed abnormalities in behavioral tests that involve 5HT mechanisms. In the elevated plus maze, males treated with CPF spent more time in the open arms, an effect seen with 5HT deficiencies in animal models of depression. Similarly, in an anhedonia test, the CPF-exposed group showed a decreased preference for chocolate milk versus water. Developmental CPF exposure also has lasting effects on cognitive function. We replicated our earlier finding that developmental CPF exposure ablates the normal sex differences in 16-arm radial maze learning and memory: during acquisition training, control male rats typically perform more accurately than do control females, but CPF treatment eliminated this normal sex difference. Females exposed to CPF showed a reduction in working and reference memory errors down to the rate of control males. Conversely, CPF-exposed males exhibited an increase in working and reference memory errors. After radial-arm acquisition training, we assessed the role of 5HT by challenging the animals with the 5HT(2) receptor antagonist ketanserin. Ketanserin did not affect performance in controls but elicited dose-dependent increases in working and reference memory errors in the CPF group, indicating an abnormal dependence on 5HT systems. Our results indicate that neonatal CPF exposures, classically thought to be subtoxic, produce lasting changes in 5HT-related behaviors that resemble animal models of depression

Long-Term Effects of Chronic Intermittent Ethanol Exposure in Adolescent and Adult Rats: Radial-Arm Maze Performance and Operant Food Reinforced Responding

Background: Adolescence is not only a critical period of late-stage neurological development in humans, but is also a period in which ethanol consumption is often at its highest. Given the prevalence of ethanol use during this vulnerable developmental period we assessed the long-term effects of chronic intermittent ethanol (CIE) exposure during adolescence, compared to adulthood, on performance in the radial-arm maze (RAM) and operant food-reinforced responding in male rats. Methodology/Principal Findings: Male Sprague Dawley rats were exposed to CIE (or saline) and then allowed to recover. Animals were then trained in either the RAM task or an operant task using fixed- and progressive- ratio schedules. After baseline testing was completed all animals received an acute ethanol challenge while blood ethanol levels (BECs) were monitored in a subset of animals. CIE exposure during adolescence, but not adulthood decreased the amount of time that animals spent in the open portions of the RAM arms (reminiscent of deficits in risk-reward ntegration) and rendered animals more susceptible to the acute effects of an ethanol challenge on working memory tasks. The operant food reinforced task showed that these effects were not due to altered food motivation or to differential sensitivity to the nonspecific performance-disrupting effects of ethanol. However, CIE pre-treated animals had lower BEC levels than controls during the acute ethanol challenges indicating persistent pharmacokinetic tolerance to ethanol after the CIE treatment. There was little evidence of enduring effects of CIE alone on traditional measures of spatial and working memory. Conclusions/Significance: These effects indicate that adolescence is a time of selective vulnerability to the long-term effects of repeated ethanol exposure on neurobehavioral function and acute ethanol sensitivity. The positive and negative findings reported here help to further define the nature and extent of the impairments observed after adolescent CIE and provide direction for future research

Liver genomic responses to ciguatoxin: evidence for activation of Phase I and Phase II detoxification pathways following an acute hypothermic response in mice

Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p ≤ 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Data were filtered (|fold change| ≥ 1.5 and p ≤ 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4°C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice

Comparative Developmental Neurotoxicity of Organophosphate Insecticides: Effects on Brain Development Are Separable from Systemic Toxicity

A comparative approach to the differences between systemic toxicity and developmental neurotoxicity of organophosphates is critical to determine the degree to which multiple mechanisms of toxicity carry across different members of this class of insecticides. We contrasted neuritic outgrowth and cholinergic synaptic development in neonatal rats given different organophosphates (chlorpyrifos, diazinon, parathion) at doses spanning the threshold for impaired growth and viability. Animals were treated daily on postnatal days 1–4 by subcutaneous injection so as to bypass differences in first-pass activation to the oxon or catabolism to inactive products. Evaluations occurred on day 5. Parathion (maximum tolerated dose, 0.1 mg/kg) was far more systemically toxic than was chlorpyrifos or diazinon (maximum tolerated dose, 1–5 mg/kg). Below the maximum tolerated dose, diazinon impaired neuritic outgrowth in the forebrain and brainstem, evidenced by a deficit in the ratio of membrane protein to total protein. Diazinon also decreased choline acetyltransferase activity, a cholinergic neuronal marker, whereas it did not affect hemicholinium-3 binding to the presynaptic choline transporter, an index of cholinergic neuronal activity. There was no m(2)-muscarinic acetylcholine receptor down-regulation, as would have occurred with chronic cholinergic hyper-stimulation. The same pattern was found previously for chlorpyrifos. In contrast, parathion did not elicit any of these changes at its maximum tolerated dose. These results indicate a complete dichotomy between the systemic toxicity of organophosphates and their propensity to elicit developmental neurotoxicity. For parathion, the threshold for lethality lies below that necessary for adverse effects on brain development, whereas the opposite is true for chlorpyrifos and diazinon