Arterial reactivity is enhanced in genetic males taking high dose estrogens

OBJECTIVES: We sought to assess whether high dose estrogen treatment is associated with enhanced arterial reactivity in genetic males. BACKGROUND: Although estrogens have been shown to enhance arterial reactivity in women, and are thereby thought to confer cardiovascular benefit, the vascular effects of long-term estrogen therapy in genetic males is unknown. METHODS: We studied the arterial physiology of 30 genetic males--15 male to female transsexuals receiving long-term high dose estrogen therapy and 15 healthy male control subjects matched for age, smoking history and vessel size. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilation [EDD]) and after nitroglycerin (GTN), an endothelium-independent dilator. Blood pressure, cholesterol and testosterone levels were also measured in each subject. RESULTS: Total testosterone and free testosterone index levels were lower in the transsexuals compared with the control subjects (p < 0.001). In contrast, EDD was significantly higher in the transsexuals than in the control males (mean [+/-SD] 7.1 +/- 3.1% vs. 3.2 +/- 2.8%, p = 0.001), as was the GTN response (21.2 +/- 6.7% vs. 14.6 +/- 3.3%, p = 0.002). Total and high density lipoprotein cholesterol, blood pressure levels and baseline vessel size were similar in the two groups. On multivariate analysis, enhanced EDD was associated independently with estrogen therapy (p = 0.02) and with low total cholesterol (p = 0.04). An enhanced GTN response was also significantly associated with estrogen therapy (p = 0.03). CONCLUSIONS: Long-term treatment with high dose estrogens is associated with enhanced arterial reactivity in genetic males, which may be due to the effects of estrogen excess or androgen deprivation, or both.     

The D2 autoreceptor agonists SND 919 and PD 128483 decrease stereotypy in developing rats

Although stereotyped behavior in adult rats is partly regulated by dopamine (DA) D2 autoreceptors, previous attempts to demonstrate D2 autoreceptor regulation of stereotypy in developing rats have been unsuccessful. In the present study, two highly selective D2 autoreceptor agonists were used to demonstrate D2 autoreceptor regulation of spontaneous stereotyped behavior in developing rats. Both SND 919 and PD 128483 produced significant dose-dependent decreases in the stereotypy counts of 21-day-old, 35-day-old, and adult rats. There was a 51% decrease in the stereotypy counts of 21-day-old rats injected with SND 919, 0.05 mg/kg, compared to a 36% decrease in the counts of rats pretreated with haloperidol. Similarly, PD 128483 significantly decreased the stereotypy counts of 21-, 35-day-old, and adult rats in a dose-dependent fashion. There was a 58% decrease in the stereotypy counts of 21-day-old rats injected with PD 128483, 0.1 mg/kg, compared to a 17% decrease in counts when the rats were first treated with haloperidol. The effect of haloperidol plus PD 128483 was significantly different from the effect of PD 128483 alone. Injection of SND 919 or PD 128483 had no significant effects on the stereotypy counts of 10-day-old rats. The results suggest that DA D2 autoreceptor-mediated regulation of spontaneous stereotyped behavior is functional at 21, but not 10, days of age.     

How are bitter and sweet tastes related?

Sweet taste and bitter taste are both apparently mediated by G-protein-coupled receptors. In this review article, connections between bitter taste and sweet taste are examined. In addition, several ways in which sweet taste may be more effectively used to mask bitter taste are discussed.     

The effects of chronic high dose androgen or estrogen treatment on the human prostate [corrected

Prostate development and disease are androgen dependent. However, the nature of hormonal effects on the prostate of healthy young men is not clear. We, therefore, measured prostate size in males chronically exposed to high doses of androgens (AS; habitual anabolic steroid abusers; n = 15) or estrogens (E; male to female transsexuals; n = 11) and compared the results with those in age-matched healthy eugonadal men without known prostate disorders. Prostate size was measured by planimetric ultrasound as cross-sectional areas and maximal dimensions in three orthogonal dimensions with a 7.5-megahertz B-mode sector scanner biplane in a transrectal transducer at 2.5 mm steps from the base to the apex of prostate. Total prostate volume (TPV) was reconstructed from planimetric sections, central prostate volume (CPV) was calculated by the ellipsoidal formula from the appropriate three maximum dimensions, and peripheral prostate volume was determined by the difference between TPV and CPV. Compared with age-matched controls, TPV was normal (-2%) in AS (P = 0.752) and reduced by 31% in E (P = 0.002), whereas CPV was increased by 20% in AS (P = 0.002) and reduced by 46% in E (P = 0.002), and the ratio of CPV/peripheral prostate volume was increased by 77% in AS (P < 0.001) and decreased by 33% in E (P = 0.047). Blood sex hormone-binding globulin was elevated by nearly 500% in E (P < 0.001), but was reduced by 47% in AS (P = 0.003). Prostate-specific antigen was normal (-6%) in AS (P = 0.799) and decreased by 86% in E (P = 0.002). Prostatic acid phosphatase was increased by 26% in AS (P = 0.007), but was unchanged (-28%) in E (P = 0.106). Total and free testosterone levels were reduced to castrate levels in E, whereas LH, FSH, and total testosterone levels were significantly reduced in AS. We conclude that in the human prostate of young men, CPV is more hormonally sensitive than TPV, and during high dose treatment, CPV is preferentially increased by chronic androgen treatment and decreased by chronic estrogen treatment. The reduction of TPV by estrogens was less than expected if solely attributable to inhibition of endogenous gonadotropin and testosterone secretion, suggesting that estrogens also have a positive effect on the normal human prostate. The reversibility and long term significance of androgen-induced stimulation of CPV and, in particular, its relationship to the onset and severity of benign prostatic hyperplasia remain to be clarified.     

Nuclear fuel considerations for the 21 century

There are many external influences that may control the path that nuclear power deployment follows. In the next 50 years several events may unfold. Fear of the consequences of the greenhouse effect may produce a carbon tax that would make nuclear power economically superior very quickly. This, in turn, would increase the rate at which uranium reserves diminish due to the increased rate of nuclear power deployment. However, breakthroughs in the extraction of uranium from the sea or deployment of fast breeder reactors would greatly extend the uranium reserves and, as well, utilize the thorium cycle.On the other hand, carbon sequestering technology breakthroughs could keep fossil fuels dominant for the remainder of the century. Nuclear power may only then continue, as today, in a lesser role or even diminish. Fusion power or new developments in solar power could completely displace nuclear power as we know it today.Even more difficult to predict is when the demand for mobile fuel for transportation will develop such that hydrogen and hydrogen rich fuel cells will be in common use. When this happens, nuclear power may be the energy source of choice to produce this fuel from water or methane. In a similar vein, the demand for potable and irrigation water may be another driver for the advent of increased deployment of nuclear power.With all these possibilities of events that could happen it appears impossible to predict with any certainty which path nuclear power deployment may take. However, it is necessary to define a strategy that is flexible enough to insure that when a technology is needed, it is ready to be deployed.For the next few decades there will be an evolutionary improvement in the performance of uranium oxide and mixed uranium oxide-plutonium oxide (MOX) LWR fuels. These improvements will be market driven to keep the cost of fuel and the resulting cost of nuclear power electricity as competitive as possible. The development of fuels for accelerator transmutation and for reactor transmutation with inert matrix fuels is in its infancy. A great deal of research has been initiated in a number of countries, which has been summarized in recent conferences. In Europe the work on these fuels is directed at the same problem as their utilization of MOX; namely to reduce the inventory of separated plutonium, minor actinides, and Long Lived Fission Products (LLFP). In the United States there is no reprocessing and thus no inventory of separated civilian plutonium. However, in the United States there is a resistance to a permanent spent fuel repository and thus accelerator transmutation presents a possible alternative. If nuclear power does have a long-term future, then the introduction of the fast reactor is inevitable. Included in the mission of the fast reactors would be the elimination of the inventory of separated plutonium while generating useful energy. The work that is ongoing now on the development of fuel concepts for assemblies that contain actinides and LLFP would be useful for fast reactor transmutation.There is still a great deal of work required to bring the fast breeder reactor option to maturity. Fortunately there is perhaps a fifty-year period to accomplish this work before fast breeders are necessary. With regard to fast reactor fuel development, future work should be considered in three stages. First, all the information obtained over the past forty years of fast reactor fuel development should be completely documented in a manner that future generations can readily retrieve and utilize the information. Fast reactor development came to such an abrupt halt world-wide that a great deal of information is in danger of being lost because most of the researchers and facilities are rapidly disappearing. Secondly, for all of the existing fast reactor fuels, and this includes, oxides, carbides, nitrides, and metallic fuels, the evolutionary work was far from being completed. Although mixed oxide fuels were probably the furthest advanced, there were many concepts for improved claddings and advanced fabrication methods that were never fully explored. Finally, with such an extended period before fast reactors are needed there is ample time for truly innovative fuels to be developed that are capable of performing over a wide range of conditions and coolants.     

Logistic regression analysis of twin data: estimation of parameters of the multifactorial liability-threshold model

This study with the rat evaluated the contribution of omega-conotoxin GVIA-(omega-CgTx) and verapamil-sensitive Ca2+ channels in behavioural, antinociceptive and thermoregulatory responses to intracerebroventricular (i.c.v.) injection of [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) and dynorphin A-(1-17), which are selective agonists for putative mu, delta and kappa-opioid receptors, respectively. The rats treated with omega-CgTx (8-32 pmol i.c.v.) showed transient, dose-dependent shaking behaviour, hyperalgesia and hypothermia which gradually disappeared within 4 h. The behaviour of the rats was normal by 24 h. Histological examination of brain sections showed morphological alterations of neurons in the hippocampus, medial-basal hypothalamus and pyriform cortex. antinociception, catalepsy and thermoregulatory responses elicited by DAMGO (0.4 and 2.0 nmol) were significantly prolonged and potentiated by verapamil (20 pmol i.c.v. 15 min before) or omega-CgTx (8 pmol 24 h before). Antinociception and hypothermia induced by DPDPE were antagonized by verapamil and omega-CgTx, whereas only omega-CgTx prevented the behavioural arousal observed after DPDPE. Similarly, hypothermia induced by dynorphin A-(1-17) (5.0 nmol) and by the kappa-opioid receptor agonist U50,488H (215 nmol) was antagonized by the two Ca2+ channel blockers but only omega-CgTx prevented the barrel rolling and bizarre postures caused by the opioid peptide.     

Collaborative test of determination of iodine value in fish oils. 1. Reaction time and carbon tetrachloride or cyclohexane as solvents

Twenty-two laboratories participated in a collaborative test to determine the iodine value (IV) of eight samples of fish oil (four with IV<150, four with IV>150) with either carbon tetrachloride (AOCS Official Method Cd 1–25) or cyclohexane (AOCS Recommended Practice Cd 1b-87) as solvent and either 1 or 2 h of reaction time. Laboratories received coded duplicate samples (hidden duplicates) and carried out duplicate determinations on each oil by each solvent-time combination (open duplicates). Replacing carbon tetrachloride with cyclohexane resulted in a lower IV (P<0.001). The decrease averaged 1.6 IV units for low-IV oils and 3.8 IV units for high-IV oils; this difference in response of 2.2 IV units between low- and high-IV oils was significant (P<0.001). Increasing the reaction time had a relatively small effect (0.34±0.18). There was no interaction of reaction time with solvent or oil type. Cyclohexane caused emulsions, which made it difficult to titrate residual iodine and thus increased the variability of the determination. The repeatability standard deviations (s _r ), based on hidden duplicates, for 1-h reaction time with carbon tetrachloride and cyclohexane were 2.17 and 3.35, respectively. The corresponding reproducibility standard deviations were 2.73 and 4.53.     

Using a virtual environment to assess cognition in the elderly

Early diagnosis of Alzheimer’s disease (AD) is essential if treatments are to be administered at an earlier point in time before neurons degenerate to a stage beyond repair. In order for early detection to occur tools used to detect the disorder must be sensitive to the earliest of cognitive impairments. Virtual reality technology offers opportunities to provide products which attempt to mimic daily life situations, as much as is possible, within the computational environment. This may be useful for the detection of cognitive difficulties. We develop a virtual simulation designed to assess visuospatial memory in order to investigate cognitive function in a group of healthy elderly participants and those with a mild cognitive impairment (MCI). Participants were required to guide themselves along a virtual path to reach a virtual destination which they were required to remember. The preliminary results indicate that this virtual simulation has the potential to be used for detection of early AD since significant correlations of scores on the virtual environment with existing neuropsychological tests were found. Furthermore, the test discriminated between healthy elderly participants and those with a MCI.     

Effects of mite resistance mechanism of geraniums on mortality and behavior of foxglove aphid (Acyrthosiphon solani Kaltenbach)

Geraniums (Pelargonium xhortorum Bailey) possess a pest-resistance mechanism, based on glandular trichomes and the exudate they produce, that has been shown to be effective against the two-spotted spider mite (Tetranychus urticae Koch). Using an intact plant bioassay, the effectiveness of the resistance mechanism was determined for another potential pest, the foxglove aphid (Acyrthosiphon solani Kaltenbach). Comparisons were made between plant lines previously analyzed for their degree of resistance to mites, as well as their glandular trichome density and trichome exudate production. Over 100 aphid adults were bioassayed on each of the five plant lines used in the experiment. In addition to adult aphid survival, the production and survival of nymphs was determined in this bioassay. The results indicate that plant lines that are resistant to the two-spotted spider mite are also resistant to the foxglove aphid, while lines susceptible to mites are susceptible to the aphids. To evaluate the physical impediment features of the trichome exudate, the behavior of foxglove aphid nymphs was compared on two geranium lines, one a resistant line with high trichome densities and large quantities of exudate and the second a susceptible line with few trichomes and reduced exudate. A third leaf surface type was produced by washing the exudate from resistant leaves using a mildly basic buffer solution prior to the bioassay. Aphid behavior was divided into five categories: feeding or probing, resting, wandering, struggling, and immobilized. On both susceptible leaves and resistant leaves from which the exudate had been removed by washing, the aphids settled quickly and were observed with inserted stylets during most of the observation intervals. In contrast, aphids on the unwashed resistant leaf surfaces often became ensnared in the sticky trichome exudate and had difficulty in settling to probe the leaf. Physical entrapment by glandular trichome exudate appears to be an important aspect of aphid resistance in geraniums.     

Replication-Based Fault Tolerance for MPI Applications

As computational clusters increase in size, their mean time to failure reduces drastically. Typically, checkpointing is used to minimize the loss of computation. Most checkpointing techniques, however, require central storage for storing checkpoints. This results in a bottleneck and severely limits the scalability of checkpointing, while also proving to be too expensive for dedicated checkpointing networks and storage systems. We propose a scalable replication-based MPI checkpointing facility. Our reference implementation is based on LAM/MPI; however, it is directly applicable to any MPI implementation. We extend the existing state of fault-tolerant MPI with asynchronous replication, eliminating the need for central or network storage. We evaluate centralized storage, a Sun-X4500-based solution, an EMC storage area network (SAN), and the Ibrix commercial parallel file system and show that they are not scalable, particularly after 64 CPUs. We demonstrate the low overhead of our checkpointing and replication scheme with the NAS Parallel Benchmarks and the High-Performance LINPACK benchmark with tests up to 256 nodes while demonstrating that checkpointing and replication can be achieved with a much lower overhead than that provided by current techniques. Finally, we show that the monetary cost of our solution is as low as 25 percent of that of a typical SAN/parallel-file-system-equipped storage system.