On the origins of fatigue strength in crystalline metallic materials.

Metallic materials experience irreversible deformation with increasing applied stress, manifested in localized slip events that result in fatigue failure upon repeated cycling. We discerned the physical origins of fatigue strength in a large set of face-centered cubic, hexagonal close-packed, and body-centered cubic metallic materials by considering cyclic deformation processes at nanometer resolution over large volumes of individual materials at the earliest stages of cycling. We identified quantitative relations between the yield strength and the ultimate tensile strength, fatigue strength, and physical characteristics of early slip localization events. The fatigue strength of metallic alloys that deform by slip could be predicted by the amplitude of slip localization during the first cycle of loading. Our observations provide a physical basis for well-known empirical fatigue laws and enable a rapid method of predicting fatigue strength as reflected by measurement of slip localization amplitude.

All fiber-coupled, long-term stable timing distribution for free-electron lasers with few-femtosecond jitter.

We report recent progress made in a complete fiber-optic, high-precision, long-term stable timing distribution system for synchronization of next generation X-ray free-electron lasers. Timing jitter characterization of the master laser shows less than 170-as RMS integrated jitter for frequencies above 10 kHz, limited by the detection noise floor. Timing stabilization of a 3.5-km polarization-maintaining fiber link is successfully achieved with an RMS drift of 3.3 fs over 200 h of operation using all fiber-coupled elements. This all fiber-optic implementation will greatly reduce the complexity of optical alignment in timing distribution systems and improve the overall mechanical and timing stability of the system.

Chronic impairments in spatial learning and memory in rats previously exposed to chlorpyrfos or diisopropylfluorophosphate.

The acute toxicity of organophosphates (OPs) has been studied extensively; however, much less attention has been given to the subject of repeated exposures that are not associated with overt signs of toxicity (i.e., subthreshold exposures). The objective of this study was to determine if the protracted spatial learning impairments we have observed previously after repeated subthreshold exposures to the insecticide chlorpyrifos (CPF) or the alkylphosphate OP, diisopropylfluorophosphate (DFP) persisted for longer periods after exposure. Male Wistar rats (beginning at two months of age) were initially injected subcutaneously with CPF (10.0 or 18.0mg/kg) or DFP (0.25 or 0.75 mg/kg) every other day for 30 days. After an extended OP-free washout period (behavioral testing begun 50 days after the last OP exposure), rats previously exposed to CPF, but not DFP, were impaired in a radial arm maze (RAM) win-shift task as well as a delayed non-match to position procedure. Later experiments (i.e., beginning 140 days after the last OP exposure) revealed impairments in the acquisition of a water maze hidden platform task associated with both OPs. However, only rats previously exposed to DFP were impaired in a second phase of testing when the platform location was changed (indicative of deficits of cognitive flexibility). These results indicate, therefore, that repeated, subthreshold exposures to CPF and DFP may lead to chronic deficits in spatial learning and memory (i.e., long after cholinesterase inhibition has abated) and that insecticide and alkylphosphate-based OPs may have differential effects depending on the cognitive domain evaluated.

Acute hemodynamic changes after rapid intravenous bolus dosing of dexmedetomidine in pediatric heart transplant patients undergoing routine cardiac catheterization.

BACKGROUND: Dexmedetomidine is a highly selective α(2)-adrenoceptor agonist with sedative, anxiolytic, and analgesic properties that has minimal effects on respiratory drive. Its sedative and hypotensive effects are mediated via central α(2A) and imidazoline type 1 receptors while activation of peripheral α(2B)-adrenoceptors result in an increase in arterial blood pressure and systemic vascular resistance. In this randomized, prospective, clinical study, we attempted to quantify the short-term hemodynamic effects resulting from a rapid i.v. bolus administration of dexmedetomidine in pediatric cardiac transplant patients. METHODS: Twelve patients, aged 10 years or younger, weighing ≤40 kg, presenting for routine surveillance of right and left heart cardiac catheterization after cardiac transplantation were enrolled. After an inhaled or i.v. induction, the tracheas were intubated and anesthesia was maintained with 1 minimum alveolar concentration of isoflurane in room air, fentanyl (1 µg/kg), and rocuronium (1 mg/kg). At the completion of the planned cardiac catheterization, 100% oxygen was administered. After recording a set of baseline values that included heart rate (HR), systolic blood pressure, diastolic blood pressure, central venous pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, pulmonary artery wedge pressure, and thermodilution-based cardiac output, a rapid i.v. dexmedetomidine bolus of either 0.25 or 0.5 µg/kg was administered over 5 seconds. The hemodynamic measurements were repeated at 1 minute and 5 minutes. RESULTS: There were 6 patients in each group. Investigation suggested that systolic blood pressure, diastolic blood pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, pulmonary artery wedge pressure, and systemic vascular resistance all increased at 1 minute after rapid i.v. bolus for both doses and decreased significantly to near baseline for both doses by 5 minutes. The transient increase in pressures was more pronounced in the systemic system than in the pulmonary system. In the systemic system, there was a larger percent increase in the diastolic pressures than the systolic pressures. Cardiac output, central venous pressure, and pulmonary vascular resistance did not change significantly. HR decreased at 1 minute for both doses and was, within the 0.5 µg/kg group, the only hemodynamic variable still changed from baseline at the 5-minute time point. CONCLUSION: Rapid i.v. bolus administration of dexmedetomidine in this small sample of children having undergone heart transplants was clinically well tolerated, although it resulted in a transient but significant increase in systemic and pulmonary pressure and a decrease in HR. In the systemic system, there is a larger percent increase in the diastolic pressures than the systolic pressures and, furthermore, these transient increases in pressures were more pronounced in the systemic system than in the pulmonary system.

The lakes of Titan.

The surface of Saturn's haze-shrouded moon Titan has long been proposed to have oceans or lakes, on the basis of the stability of liquid methane at the surface. Initial visible and radar imaging failed to find any evidence of an ocean, although abundant evidence was found that flowing liquids have existed on the surface. Here we provide definitive evidence for the presence of lakes on the surface of Titan, obtained during the Cassini Radar flyby of Titan on 22 July 2006 (T16). The radar imaging polewards of 70 degrees north shows more than 75 circular to irregular radar-dark patches, in a region where liquid methane and ethane are expected to be abundant and stable on the surface. The radar-dark patches are interpreted as lakes on the basis of their very low radar reflectivity and morphological similarities to lakes, including associated channels and location in topographic depressions. Some of the lakes do not completely fill the depressions in which they lie, and apparently dry depressions are present. We interpret this to indicate that lakes are present in a number of states, including partly dry and liquid-filled. These northern-hemisphere lakes constitute the strongest evidence yet that a condensable-liquid hydrological cycle is active in Titan's surface and atmosphere, in which the lakes are filled through rainfall and/or intersection with the subsurface 'liquid methane' table.

Titan Radar Mapper observations from Cassini's T3 fly-by.

Cassini's Titan Radar Mapper imaged the surface of Saturn's moon Titan on its February 2005 fly-by (denoted T3), collecting high-resolution synthetic-aperture radar and larger-scale radiometry and scatterometry data. These data provide the first definitive identification of impact craters on the surface of Titan, networks of fluvial channels and surficial dark streaks that may be longitudinal dunes. Here we describe this great diversity of landforms. We conclude that much of the surface thus far imaged by radar of the haze-shrouded Titan is very young, with persistent geologic activity.

The sand seas of Titan: Cassini RADAR observations of longitudinal dunes.

The most recent Cassini RADAR images of Titan show widespread regions (up to 1500 kilometers by 200 kilometers) of near-parallel radar-dark linear features that appear to be seas of longitudinal dunes similar to those seen in the Namib desert on Earth. The Ku-band (2.17-centimeter wavelength) images show approximately 100-meter ridges consistent with duneforms and reveal flow interactions with underlying hills. The distribution and orientation of the dunes support a model of fluctuating surface winds of approximately 0.5 meter per second resulting from the combination of an eastward flow with a variable tidal wind. The existence of dunes also requires geological processes that create sand-sized (100- to 300-micrometer) particulates and a lack of persistent equatorial surface liquids to act as sand traps.

Cassini radar views the surface of Titan.

The Cassini Titan Radar Mapper imaged about 1% of Titan's surface at a resolution of approximately 0.5 kilometer, and larger areas of the globe in lower resolution modes. The images reveal a complex surface, with areas of low relief and a variety of geologic features suggestive of dome-like volcanic constructs, flows, and sinuous channels. The surface appears to be young, with few impact craters. Scattering and dielectric properties are consistent with porous ice or organics. Dark patches in the radar images show high brightness temperatures and high emissivity and are consistent with frozen hydrocarbons.

Effect of steroids and nitric oxide on pituitary hormone release in ovariectomized, peripubertal rats.

The purpose of this study was to determine the effects of the duration of steroid depletion on the steroid-induced luteinizing hormone and prolactin surges in ovariectomized, peripubertal female rats. Additionally, the role of nitric oxide (NO) in mediating the surge responses was determined. Peripubertal, 6-week-old, female Sprague-Dawley rats were ovariectomized. One or three weeks later, animals were injected with 17 beta-estradiol (50 microg, sc) followed 48 h later by progesterone (2.5 mg, sc). Effects of NO were examined by administering L-arginine (300 mg/kg, ip). The response of ovariectomized, adult females to steroid treatment was also determined. One and three weeks after ovariectomy, steroid replacement produced an LH and prolactin surge in peripubertal animals. However, both the magnitude and duration of the LH surge was greater 3 weeks after ovariectomy. While L-arginine significantly enhanced the magnitude of the LH surge 1 week after ovariectomy, by 3 weeks L-arginine caused a decrease in the duration, but not the magnitude of the surge. In contrast, L-arginine did not affect either the magnitude or duration of the prolactin surge one week after ovariectomy, but diminished the magnitude after 3 weeks of steroid depletion. In adults, steroids induced significant increases in both LH and prolactin. These results demonstrate that sensitivity to NO stimulation of LH, but not prolactin secretion, is modulated by the duration of gonadal steroid hormone depletion. The differences in the responsiveness of LH and prolactin to steroid-induced stimulation in peripubertal animals demonstrate that these hormones are regulated by NO through different mechanisms.

Effects of cyclic steroid hormone replacement on prolactin and luteinizing hormone surges in female rats.

The ability of steroid hormones to produce an LH or prolactin (PRL) surge was determined in rats ovariectomized at 6, 9 or 13 weeks of age and subjected to one, three or six cycles of estrogen and progesterone replacement. Sensitivity to steroid replacement was dependent on the age of the animal at the time of ovariectomy. Repeated cyclic steroid hormone replacement significantly increased the magnitude of the PRL response, but not the LH response, in animals ovariectomized at 6 weeks. The LH response was significantly altered by cyclic steroid replacement only in animals ovariectomized at 13 weeks. These results indicate that the mechanisms involved in the regulation of PRL secretion are influenced by steroid hormone replacement and that cyclic steroid hormone exposure increases the magnitude of the PRL secretory response.

Mechanisms of reproductive suppression in female pine voles (Microtus pinetorum).

In co-operatively breeding birds and mammals, philopatric females are often reproductively suppressed. Many studies have focused on the functional significance of reproductive suppression, but further investigation of the mechanisms involved is required for a complete understanding of this process. This study investigated whether reproductive suppression in non-reproductive female pine voles (Microtus pinetorum) occurs as a result of lack of gamete maturation or lack of increase in LH. The behaviour of male pine voles was also examined to determine whether they show a preference for the mother versus her daughter, as lack of male stimulation may inhibit an increase of LH in daughter pine voles. Ovarian development and circulating LH concentrations were investigated in females housed with a prospective mate in the presence or absence of a parent. Maturation of gametes was not affected by the presence of a parent. In the presence of the mother, there was no increase in LH, as was observed in females housed with or exposed to a novel male. Males spent more time with mothers and possibly showed a preference for mating with the mother. These results are consistent with the contention that ovulation does not occur in female pine voles housed in the presence of their mother; however, it is not clear whether the lack of ovulation is caused by lack of stimulation from the male or suppression by the mother.

Design and evaluation of a breath-analysis system for biological monitoring of volatile compound.

To ensure the health and safety of workers, integrated industrial hygiene methodologies often include biological monitoring of the workers to help understand their exposure to chemicals. To this end, a field-portable breath-analysis system was developed and tested to measure selected solvents in exhaled air. The exhaled breath data were evaluated using a physiologically based pharmacokinetic (PBPK) model to relate exposure to tissue dose. The system was designed to monitor workers every time they entered or left a work environment--a vast improvement over current 8-hour integrated monitoring strategies. The system combines (1) chemical dosimeters to measure airborne contaminant levels (analyzed in the field/ workplace); (2) real-time breath analysis to quantitate exposure; and 3) PBPK models to estimate internal target tissue dose. To evaluate the system, field tests were conducted at two locations: (1) at an incinerator in Tennessee monitoring benzene and toluene exposures; and (2) a waste repackaging facility in Washington State where hexane, trimethylbenzene, and methylene chloride was monitored. Exhaled breath was sampled and analyzed before and after each specific job task, which ranged from 15 min to 8 hours in duration. In both field studies several volunteers had posttask breath levels higher than pretask levels. The greatest increase corresponded to 573 ppb for methylene chloride and 60 ppb for toluene. Compared with breath analysis, the chemical dosimeters underpredicted the dosimetry, particularly for longer sampling intervals when the volume of air sampled may have diluted exposures. The results of the field studies illustrate the utility of monitoring workers for exposures throughout the day, particularly when job-specific tasks may indicate a potential for exposure.

Cervical pathology in West Virginia adolescents.

Cytologic screening is an important diagnostic tool used to detect precancerous and cancerous lesions of the cervix. We studied the prevalence of cervical abnormalities, based on Pap smear results, in patients at the Outpatient Adolescent Clinic at West Virginia University. We found a high incidence of overall intraepithelial cell pathology (24%) in this group with 2.4% high grade and 9.9% low-grade lesions. These findings show that major cervical pathology is present in this age group. Furthermore, repeat smears at intervals of < one year were performed on 317 patients. Of these repeat smears, 7% changed from normal to abnormal in this period. Sexually active adolescent females should have Pap smears at least annually to detect abnormalities that may otherwise not be detected until they are more advanced and difficult to manage. Higher risk adolescents may need semiannual screening.

Immunoneutralization of endogenous opioid peptides prevents the suckling-induced prolactin increase and the inhibition of tuberoinfundibular dopaminergic neurons.

Previous studies have shown that the endogenous opioid peptides, acting at specific opiate receptor subtypes, are involved in the suckling-induced prolactin secretory response. The prolactin increase elicited by suckling is due, at least in part, to an inhibition of tuberoinfundibular dopaminergic (TIDA) neurons in the hypothalamus. We investigated the effects of immunoneutralization of dynorphin, leu-enkephalin and met-enkephalin on the suckling-induced prolactin increase and on the activity of the TIDA neurons in lactating female rats between days 7 and 12 postpartum. Rats were injected into the right lateral ventricle with antiserum specific for one of these three peptides. Control rats were administered equal amounts of immunoglobulin proteins. Suckling produced a profound and significant increase in prolactin levels, as well as a decrease in DOPA accumulation in the median eminence of lactating rats. Administration of immunoglobulin concentrations of up to 3.6 microg did not inhibit the prolactin secretory response to the suckling stimulus and did not prevent the suckling-induced inhibition of TIDA neurons. Antisera to all three endogenous opioid peptides abolished the suckling-induced prolactin increase and prevented the inhibition in DOPA accumulation in the median eminence. Thus, the endogenous opioid peptides, dynorphin, leu-enkephalin and met-enkephalin, are essential for the prolactin secretory response to suckling and inhibition of TIDA neuronal activity is at least one of the mechanisms of action utilized by these peptides.

Multisite evaluation of a new diabetes self-test for glucose and glycated protein (fructosamine).

BACKGROUND: In diabetes management, the true average blood glucose is best obtained using glycated protein tests that give the average blood glucose over a previous time window of either weeks (fructosamine tests) or months (glycated hemoglobin tests). Until now, glycated protein tests have only been available as laboratory tests and have therefore been underutilized in diabetes management. Recently, a fructosamine self-test for use by diabetes patients at home was cleared for marketing by the U.S. Food and Drug Administration (FDA). We have studied the performance of this test in three geographically distinct diabetes clinics to confirm the performance and accuracy of both glucose and fructosamine testing with this device. This new self-testing system has the potential to improve glycemic control dramatically in patients with diabetes, including those patients with type 2 diabetes using oral drug therapy. METHODS: Three geographically different sites (San Diego, CA, Tallahassee, FL, and Minneapolis, MN) were selected for the study. Sixty male and 56 female adult patients, with both type 1 (59) and type 2 (57) diabetes, were selected for participation in the study (total patients = 116). Fingerstick puncture capillary blood glucose was tested using the YSI Model 1500 and the Duet Glucose test. A fingerstick puncture capillary blood test was also tested with the Duet GlucoProtein (fructosamine) test strip in duplicate. For fructosamine comparison, a venipuncture blood sample of ethylene diaminetetraacetic acid (EDTA) plasma was collected and tested using the Roche Unimate laboratory test. RESULTS: The glucose test gave excellent correlation to the reference laboratory method (r = 0.98) and the GlucoProtein test gave a correlation of 0.72 compared to the laboratory method. The bias of both tests compared to the laboratory tests was 10% or less at all concentrations. Error grid analysis of the glucose test showed that 97.5% of test results were in the accurate zone and 2.5% were in the clinically neutral or benign errors zone. Analysis of fructosamine test results using a two-by-two grid yielded sensitivity of 100%, specificity of 92% and accuracy of 94%. CONCLUSIONS: The Duet Glucose Control System is accurate for both measuring glucose and GlucoProtein (fructosamine) using a fingerstick blood sample. This new testing system has the potential to provide useful information to both healthcare specialists in their office and also to patients at home to help them achieve better long-term glucose control and avoid the potential acute and chronic complications of diabetes.

Residential environmental measurements in the national human exposure assessment survey (NHEXAS) pilot study in Arizona: preliminary results for pesticides and VOCs.

A major objective of the National Human Exposure Assessment Survey (NHEXAS) performed in Arizona was to conduct residential environmental and biomarker measurements of selected pesticides (chlorpyrifos, diazinon), volatile organic compounds (VOCs; benzene, toluene, trichloroethene, formaldehyde, 1,3-butadiene), and metals for total human exposure assessments. Both personal (e.g., blood, urine, dermal wipes, 24 h duplicate diet) and microenvironmental (e.g., indoor and outdoor air, house dust, foundation soil) samples were collected in each home in order to describe individual exposure via ingestion, inhalation, and dermal pathways, and to extrapolate trends to larger populations. This paper is a preliminary report of only the microenvironmental and dermal wipe data obtained for the target pesticides and VOCs, and provides comparisons with results from similar studies. Evaluations of total exposure from all sources and pathways will be addressed in future papers. The pesticides and VOCs all showed log-normal distributions of concentrations in the Arizona population sampled, and in most cases were detected with sufficient frequency to allow unequivocal description of the concentration by media at the 90th, 75th, and 50th (median) percentiles. Those combinations of pollutant and media, in which a large fraction of the measurements were below the detection limit of the analysis method used, included trichloroethene, 1,3-butadiene, and formaldehyde in outdoor air; chlorpyrifos and diazinon in outdoor air; and diazinon in dermal and window sill wipes. In general, indoor air concentrations were higher than outdoor air concentrations for all VOCs and pesticides investigated, and VOC levels were in good agreement with levels reported in other studies. In addition, the agreement obtained between co-located VOC samplers indicated that the low-cost diffusional badges used to measure concentrations are probably adequate for use in future monitoring studies. For the pesticides, the median levels found in indoor samples agreed well with other studies, although the levels corresponding to the upper 0.1-1% of the population were considerably higher than levels reported elsewhere, with indoor air levels as high as 3.3 and 20.5 microg/m3 for chlorpyrifos and diazinon, respectively. These data showed excellent correlation (Pearson and Spearman correlation coefficients of 0.998 and 0.998, respectively) between chlorpyrifos in indoor air and in the corresponding dermal wipes, and relatively poor correlation between chlorpyrifos in dust (microg/g or microg/ml) and dermal wipes (Pearson=0.055 microg/g and 0.015 microg/m2; Spearman=0.644 microg/g and 0.578 microg/m2). These data suggest the importance of dermal penetration of semi-volatiles as a route of residential human exposure.

Characterization of the electrophysiological and morphological properties of rat central amygdala neurons in vitro.

Forty central amygdala neurons labelled with 2% Neurobiotin were categorized according to their distinctive bioelectrical membrane properties and classified physiologically by their hyperpolarized resting membrane potential (-74 mV), short duration medium afterhyperpolarization (239.2 ms), and non-accommodating response as Type A neurons (63%; N = 25/40), or as Type B neurons (37%; N = 15/40) by their depolarized resting membrane potential (-66 mV), long slow-afterhyperpolarization (1.8 s), and accommodation response. Visualized within subnuclei of the central amygdala, Neurobiotin-labelled Type A neurons were medium-size cells [16.5 +/- 3 x 10.7 +/- 2 mu m; length x width] with smooth, spine-free ovoid, pyramiform, and fusiform perikarya. Aspinous primary dendrites gave rise to distal dendrites covered with numerous small pedunculated spines; density of spines ranged from sparse to abundant. Type B central amygdala neurons were larger cells [23.9 +/- 5 x 14.9 +/- 4 mu m] with smooth, aspinous ovoid, polygonal, and pyramiform somata. Dendrites were aspinous and covered with variably sized varicosities. Two distinct populations of neurons exist within the central amygdaloid complex: the medium-size, spine-laden Type A defined neuron with its non-accommodating electrophysiological response and the larger aspinous, varicosity-laden Type B defined neuron with its accommodating response. In contrast to their neighboring "cortical-like" amygdala neurons, central amygdala neurons possess a "striatal-like" cytoarchitecture and electrophysiology.

Polycyclic aromatic hydrocarbon exposures of children in low-income families.

Children in low-income families may have high exposures to polycyclic aromatic hydrocarbons (PAH). Such exposures could result from household proximity to heavy traffic or industrial sources, environmental tobacco smoke, contaminated house dust or soil, among others. The objectives of this study were: to establish methods for measuring total PAH exposure of children in low-income families, to estimate the PAH exposures of these children, and to estimate the relative importance of the environmental pathways for PAH exposure. Analytical methods to determine PAH in air, dust, soil, and food and to determine hydroxy-PAH in urine samples were evaluated and validated. A two-home pilot study was conducted in downtown Durham, North Carolina (NC) during February 1994. One smoker's and one nonsmoker's household, which had preschool children and income at or below the official U.S. poverty level, participated. A nine-home winter and a nine-home summer study were conducted in Durham and the NC Piedmont area during February 1995 and August 1995, respectively. A summer study in four smokers' homes was also conducted. In each of these studies, multimedia samples were collected and analyzed for PAH or hydroxy-PAH. Summary statistics, Pearson correlations, and analysis of variance were performed on the combined data from these four field studies. An effective screening method was established for recruiting low-income families. The field protocol involved measurements of three homes in 2-day periods. This protocol should be suitable for large-scale studies. The results showed that indoor PAH levels were generally higher than outdoor PAH levels. Higher indoor PAH levels were observed in the smokers' homes compared to nonsmokers' homes. Higher outdoor PAH levels were found in inner city as opposed to rural areas. The relative concentration trend for PAH in dust and soil was: house dust > entryway dust > pathway soil. The PAH concentrations in adults' food samples were generally higher than those in children's food samples. Children's potential daily doses of PAH were higher than those of adults in the same household, when intakes were normalized to body weights. Inhalation is an important pathway for children's exposure to total PAH because of the high levels of naphthalene present in both indoor and outdoor air. Dietary ingestion and nondietary ingestion pathways became more important for children's exposure to the B2 PAH (ranked as probable human carcinogens, B2 by the U.S. EPA's Integrated Risk System), most of which are of low volatility. The analysis of variance results showed that inner city participants had higher total exposure to B2 PAH than did rural participants.