CHARACTERIZATION OF THE COUNT RATE PERFORMANCE AND EVALUATION OF THE EFFECTS OF HIGH COUNT RATES ON MODERN GAMMA CAMERAS

CHARACTERIZATION OF THE COUNT RATE PERFORMANCE AND EVALUATION OF THE EFFECTS OF HIGH COUNT RATES ON MODERN GAMMA CAMERAS Michael Stephen Silosky, B.S. Supervisory Professor: S. Cheenu Kappadath, Ph.D. Evaluation of count rate performance (CRP) is an integral component of gamma camera quality assurance and measurement of system dead time (τ) is important for quantitative SPECT. The CRP of three modern gamma cameras was characterized using established methods (Decay and Dual Source) under a variety of experimental conditions. For the Decay method, input count rate was plotted against observed count rate and fit to the paralyzable detector model (PDM) to estimate τ (Rates method). A novel expression for observed counts as a function of measurement time interval was derived and the observed counts were fit to this expression to estimate τ (Counts method). Correlation and Bland-Altman analysis were performed to assess agreement in estimates of τ between methods. The dependencies of τ on energy window definition and incident energy spectrum were characterized. The Dual Source method was also used to estimate τ and its agreement with the Decay method under identical conditions and the effects of total activity and the ratio of source activities were investigated. Additionally, the effects of count rate on several performance metrics were evaluated. The CRP curves for each system agreed with the PDM at low count rates but deviated substantially at high count rates. Estimates of τ for the paralyzable portion of the CRP curves using the Rates and Counts methods were highly correlated (r=0.999) but with a small (~6%) difference. No significant difference was observed between the highly correlated estimates of τ using the Decay or Dual Source methods under identical experimental conditions (r=0.996). Estimates of τ increased as a power-law function with decreasing ratio of counts in the photopeak to the total counts and linearly with decreasing spectral effective energy. Dual Source method estimates of τ varied as a quadratic with the ratio of the single source to combined source activities and linearly with total activity used across a large range. Image uniformity, spatial resolution, and energy resolution degraded linearly with count rate and image distorting effects were observed. Guidelines for CRP testing and a possible method for the correction of count rate losses for clinical images have been proposed.

Radiocarbon dating, sedimentation rate, granulometry and organic carbon content of ODP Leg 182 sites

This data report presents sedimentological (grain size) and geochemical (X-ray diffraction, total organic carbon, accelerator mass spectrometry radiocarbon, and percent carbonate) information obtained from the western transect (Sites 1132, 1130, and 1134) and the eastern transect (Sites 1129, 1131, and 1127) in the Great Australian Bight during Leg 182. The purpose is to quantify changing rates of sediment accumulation and changes in sediment type from the late Pleistocene and Holocene, in order to relate these changes to the well-known sea level curve that exists for this time frame. Ultimately, these data can be used to more effectively interpret lithologic variations deeper in the Pleistocene succession, which most likely represent orbitally forced sea level events.

Mean snow accumulation rate, and mean methane sulfonate, chloride and nitrate concentration in snow pits and firn cores of Dronning Maud Land

We quantified postdepositional losses of methane sulfonate (MSA-), nitrate, and chloride at the European Project for Ice Coring in Antarctica (EPICA) drilling site in Dronning Maud Land (DML) (75°S, 0°E). Analyses of four intermediate deep firn cores and 13 snow pits were considered. We found that about 26 ± 13% of the once deposited nitrate and typically 51 ± 20% of MSA- were lost, while for chloride, no significant depletion could be observed in firn older than one year. Assuming a first order exponential decay rate, the characteristic e-folding time for MSA- is 6.4 ± 3 years and 19 ± 6 years for nitrate. It turns out that for nitrate and MSA- the typical mean concentrations representative for the last 100 years were reached after 5.4 and 6.5 years, respectively, indicating that beneath a depth of around 1.2-1.4 m postdepositional losses can be neglected. In the area of investigation, only MSA- concentrations and postdepositional losses showed a distinct dependence on snow accumulation rate. Consequently, MSA- concentrations archived at this site should be significantly dependent on the variability of annual snow accumulation, and we recommend a corresponding correction. With a simple approach, we estimated the partial pressure of the free acids MSA, HNO3, and HCl on the basis of Henry's law assuming that ionic impurities of the bulk ice matrix are localized in a quasi-brine layer (QBL). In contrast to measurements, this approach predicts a nearly complete loss of MSA-, NO3 - , and Cl-.

Ice loss in the Canadian Arctic Archipelago

Though much attention has been focused in recent years on the melting of ice from Greenland and Antarctica, nearly half of the ice volume currently being lost to the ocean is actually coming from other mountain glaciers and ice caps. Ice loss from a group of islands in northern Canada accounts for much of that volume. In a study published in April 2011 in the journal Nature, a team of researchers led by Alex Gardner of the University of Michigan found that land ice in both the northern and southern Canadian Arctic Archipelago has declined sharply. The maps above show ice loss from surface melting for the northern portion of the archipelago from 2004-2006 (left) and 2007-2009 (right). Blue indicates ice gain, and red indicates ice loss. In the six years studied, the Canadian Arctic Archipelago lost an average of approximately 61 gigatons of ice per year. (A gigaton is a billion tons of ice.) The research team also found the rate of ice loss was accelerating. From 2004 to 2006, the average mass loss was roughly 31 gigatons per year; from 2007 to 2009, the loss increased to 92 gigatons per year. Gardner and colleagues used three independent methods to assess ice mass, all of which showed the same trends. The team used a model to estimate the surface mass balance of ice and the amount of ice discharged. They also compiled and analyzed measurements from NASA's Ice, Cloud and Land Elevation Satellite (ICESat) to assess changes in the surface height of ice. Finally, they gathered observations from NASA's Gravity Recovery and Climate Experiment (GRACE) to determine changes in the gravity field in the region, an indicator of the amount of ice gained or lost. The Canadian Arctic Archipelago generally receives little precipitation, and the amount of snowfall changes little from year to year. But the rate of snow and ice melting varies considerably, so changes in ice mass come largely from changes in summertime melt. During the 2004 to 2009 study period, the Canadian Arctic Archipelago experienced four of its five warmest years since 1960, likely fueling the melting. Gardner notes that from 2001 to 2004, the sum of melting from all mountain glaciers and ice caps around the world (but not the Greenland and Antarctic ice sheets) contributed an estimated 1 millimeter per year to global sea level rise. Recent estimates suggest the Greenland and Antarctic ice sheets add another 1.3 millimeters per year to sea level. "This means 1 percent of the land ice volume-mountain glaciers and ice caps-account for about half of all ice loss to the world's oceans," Gardner said. "Most of the ice loss is coming from the Canadian Arctic Archipelago, Alaska, Patagonia, the Himalayas, and the smaller ice masses surrounding the main Greenland and Antarctic ice sheets."

Tab. 1: Mean water loss by mosses and lichens at 40%

The loss of water in a desiccating atmosphere (c.40% r.h. at 10°C) and uptake of water from a saturated atmosphere (100% r.h. at 10°C) was recorded at intervals over periods of many hours or days in the dominant mosses and macroiichens occurring near the Australian Casey Station. Wilkes Land, continental Antarctica. While major differences exist in the water holding capacity and rates of water loss between mosses and lichens, the minimum levels attained after prolonged exposure to desiccating conditions are remarkably similar. By contrast, the volume of water absorbed from a saturated atmosphere is very similar in both groups of cryptogams. Morphological and anatomical characters are responsible for many of the differences, both between species, and within species exhibiting different growth features. Thus, significantly larger amounts of water are held by colonies of Bryum algens with a dense tomentum of rhizoids than those with sparse rhizoids; similarly, the rhizinate Umbilicaria aprina held a greater volume of water than the erhizinate U. decussata. The filamentous mat form of Alectoria mimiscula permits a much higher water content to be attained than in the coarser fruticose forms of Usnea sphacelata and U. antarctica. The dense shoot arrangement in Schistidium antarcticum accounts for the high water holding capacity in the hydric turf form whereas the less densely packed shoots and thicker cell walls of the xeric cushion form maintain a lower water content. The rate of water loss (as percentage dry weight) was much faster in the turf form of Schistidium and tomenlose form of Bryum, although this trend was reversed when expressed as percentage of the initial water content. Minimal water contents arc achieved by the lichens in desiccating conditions within 6-12 hours, whereas the mosses take several times longer. The water relations characteristics of these cryptogams are considered in the light of their distribution in the field and of their metabolic activity under prevailing Antarctic conditions.

Employment rate impacts of charging the Heavy Good Vehicle corridor (Madrid-Sevilla) across Spanish regions: a Random Utility Based Multiregional Input-Output approach

The implementation of a charging policy for heavy goods vehicles in European Union (EU) member countries has been imposed to reflect costs of construction and maintenance of infrastructure as well as externalities such as congestion, accidents and environmental impact. In this context, EU countries approved the Eurovignette directive (1999/62/EC) and its amending directive (2006 /38/EC) which established a legal framework to regulate the system of tolls. Even if that regulation seek s to increase the efficien cy of freight, it will trigger direct and indirect effects on Spain’s regional economies by increasing transport costs. This paper presents the development of a multiregional Input-Output methodology (MRIO) with elastic trade coefficients to predict in terregional trade, using transport attributes integrated in multinomial logit models. This method is highly useful to carry out an ex-ante evaluation of transport policies because it involves road freight transport cost sensitivity, and determine regional distributive and substitution economic effect s of countries like Spain, characterized by socio-demographic and economic attributes, differentiated region by region. It will thus be possible to determine cost-effective strategies, given different policy scenarios. MRIO mode l would then be used to determine the impact on the employment rate of imposing a charge in the Madrid-Sevilla corridor in Spain. This methodology is important for measuring the impact on the employment rate since it is one of the main macroeconomic indicators of Spain’s regional and national economic situation. A previous research developed (DESTINO) using a MRIO method estimated employment impacts of road pricing policy across Spanish regions considering a fuel tax charge (€/liter) in the entire shortest cost path network for freight transport. Actually, it found that the variation in employment is expected to be substantial for some regions, and negligible for others. For example, in this Spanish case study of regional employment has showed reductions between 16.1% (Rioja) and 1.4% (Madrid region). This variation range seems to be related to either the intensity of freight transport in each region or dependency of regions to transport intensive economic sect ors. In fact, regions with freight transport intensive sectors will lose more jobs while regions with a predominantly service economy undergo a fairly insignificant loss of employment. This paper is focused on evaluating a freight transport vehicle-kilometer charge (€/km) in a non-tolled motorway corridor (A-4) between Madrid-Sevilla (517 Km.). The consequences of the road pricing policy implementation show s that the employment reductions are not as high as the diminution stated in the previous research because this corridor does not affect the whole freight transport system of Spain.

Loss of social behaviors by Myxococcus xanthus during evolution in an unstructured habitat

Social behaviors are often targets of natural selection among higher organisms, but quantifying the effects of such selection is difficult. We have used the bacterium Myxococcus xanthus as a model system for studying the evolution of social interactions. Changes in the social behaviors of 12 M. xanthus populations were quantified after 1,000 generations of evolution in a liquid habitat, in which interactions among individuals were continually hindered by shaking and low cell densities. Derived lineages were compared with their ancestors with respect to maximum growth rate, motility rates on hard and soft agar, fruiting body formation ability, and sporulation frequency during starvation. Improved performance in the liquid selective regime among evolved lines was usually associated with significant reductions in all of the major social behaviors of M. xanthus. Maintenance of functional social behaviors is apparently detrimental to fitness under asocial growth conditions.

A deletion within the murine Werner syndrome helicase induces sensitivity to inhibitors of topoisomerase and loss of cellular proliferative capacity

Werner syndrome (WS) is an autosomal recessive disorder characterized by genomic instability and the premature onset of a number of age-related diseases. The gene responsible for WS encodes a member of the RecQ-like subfamily of DNA helicases. Here we show that its murine homologue maps to murine chromosome 8 in a region syntenic with the human WRN gene. We have deleted a segment of this gene and created Wrn-deficient embryonic stem (ES) cells and WS mice. While displaying reduced embryonic survival, live-born WS mice otherwise appear normal during their first year of life. Nonetheless, although several DNA repair systems are apparently intact in homozygous WS ES cells, such cells display a higher mutation rate and are significantly more sensitive to topoisomerase inhibitors (especially camptothecin) than are wild-type ES cells. Furthermore, mouse embryo fibroblasts derived from homozygous WS embryos show premature loss of proliferative capacity. At the molecular level, wild-type, but not mutant, WS protein copurifies through a series of centrifugation and chromatography steps with a multiprotein DNA replication complex.

Evolution of plastid gene rps2 in a lineage of hemiparasitic and holoparasitic plants: Many losses of photosynthesis and complex patterns of rate variation

The plastid genomes of some nonphotosynthetic parasitic plants have experienced an extreme reduction in gene content and an increase in evolutionary rate of remaining genes. Nothing is known of the dynamics of these events or whether either is a direct outcome of the loss of photosynthesis. The parasitic Scrophulariaceae and Orobanchaceae, representing a continuum of heterotrophic ability ranging from photosynthetic hemiparasites to nonphotosynthetic holoparasites, are used to investigate these issues. We present a phylogenetic hypothesis for parasitic Scrophulariaceae and Orobanchaceae based on sequences of the plastid gene rps2, encoding the S2 subunit of the plastid ribosome. Parasitic Scrophulariaceae and Orobanchaceae form a monophyletic group in which parasitism can be inferred to have evolved once. Holoparasitism has evolved independently at least five times, with certain holoparasitic lineages representing single species, genera, and collections of nonphotosynthetic genera. Evolutionary loss of the photosynthetic gene rbcL is limited to a subset of holoparasitic lineages, with several holoparasites retaining a full length rbcL sequence. In contrast, the translational gene rps2 is retained in all plants investigated but has experienced rate accelerations in several hemi- as well as holoparasitic lineages, suggesting that there may be substantial molecular evolutionary changes to the plastid genome of parasites before the loss of photosynthesis. Independent patterns of synonymous and nonsynonymous rate acceleration in rps2 point to distinct mechanisms underlying rate variation in different lineages. Parasitic Scrophulariaceae (including the traditional Orobanchaceae) provide a rich platform for the investigation of molecular evolutionary process, gene function, and the evolution of parasitism.

Disruption of the telomerase catalytic subunit gene from Arabidopsis inactivates telomerase and leads to a slow loss of telomeric DNA

Telomerase is an essential enzyme that maintains telomeres on eukaryotic chromosomes. In mammals, telomerase is required for the lifelong proliferative capacity of normal regenerative and reproductive tissues and for sustained growth in a dedifferentiated state. Although the importance of telomeres was first elucidated in plants 60 years ago, little is known about the role of telomeres and telomerase in plant growth and development. Here we report the cloning and characterization of the Arabidopsis telomerase reverse transcriptase (TERT) gene, AtTERT. AtTERT is predicted to encode a highly basic protein of 131 kDa that harbors the reverse transcriptase and telomerase-specific motifs common to all known TERT proteins. AtTERT mRNA is 10–20 times more abundant in callus, which has high levels of telomerase activity, versus leaves, which contain no detectable telomerase. Plants homozygous for a transfer DNA insertion into the AtTERT gene lack telomerase activity, confirming the identity and function of this gene. Because telomeres in wild-type Arabidopsis are short, the discovery that telomerase-null plants are viable for at least two generations was unexpected. In the absence of telomerase, telomeres decline by approximately 500 bp per generation, a rate 10 times slower than seen in telomerase-deficient mice. This gradual loss of telomeric DNA may reflect a reduced rate of nucleotide depletion per round of DNA replication, or the requirement for fewer cell divisions per organismal generation. Nevertheless, progressive telomere shortening in the mutants, however slow, ultimately should be lethal.

Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function

During the aging process, mammals lose up to a third of their skeletal muscle mass and strength. Although the mechanisms underlying this loss are not entirely understood, we attempted to moderate the loss by increasing the regenerative capacity of muscle. This involved the injection of a recombinant adeno-associated virus directing overexpression of insulin-like growth factor I (IGF-I) in differentiated muscle fibers. We demonstrate that the IGF-I expression promotes an average increase of 15% in muscle mass and a 14% increase in strength in young adult mice, and remarkably, prevents aging-related muscle changes in old adult mice, resulting in a 27% increase in strength as compared with uninjected old muscles. Muscle mass and fiber type distributions were maintained at levels similar to those in young adults. We propose that these effects are primarily due to stimulation of muscle regeneration via the activation of satellite cells by IGF-I. This supports the hypothesis that the primary cause of aging-related impairment of muscle function is a cumulative failure to repair damage sustained during muscle utilization. Our results suggest that gene transfer of IGF-I into muscle could form the basis of a human gene therapy for preventing the loss of muscle function associated with aging and may be of benefit in diseases where the rate of damage to skeletal muscle is accelerated.

Loss of oncogenic ras expression does not correlate with loss of tumorigenicity in human cells.

ras oncogenes are mutated in at variety of human tumors, which suggests that they play an important role in human carcinogenesis. To determine whether continued oncogenic ras expression is necessary to maintain the malignant phenotype, we studied the human fibrosarcoma cell line, HT1080, which contains one mutated and one wild-type N-ras allele. We isolated a variant of this cell line that no longer contained the mutated copy of the N-ras gene. Loss of mutant N-ras resulted in cells that displayed a less transformed phenotype characterized by a flat morphology, decreased growth rate, organized actin stress fibers, and loss of anchorage-independent growth. The transformed phenotype was restored following reintroduction of mutant N-ras. Although loss of the oncogenic N-ras drastically affected in vitro growth parameters, the variant remained tumorigenic in nude mice indicating that mutated N-ras expression is not necessary for maintenance of the tumorigenic phenotype. We confirmed this latter observation in colon carcinoma cell lines that have lost activated K-ras expression via targeted knockout of the mutant K-ras gene.

Nonlinear control of heart rate variability in human infants.

Nonlinear analyses of infant heart rhythms reveal a marked rise in the complexity of the electrocardiogram with maturation. We find that normal mature infants (gestation greater than or equal to 35 weeks) have complex and distinctly nonlinear heart rhythms (consistent with recent reports for healthy adults) but that such nonlinearity is lacking in preterm infants (gestation > or = to 27 weeks) where parasympathetic-sympathetic interaction and function are presumed to be less well developed. Our study further shows that infants with clinical brain death and those treated with atropine exhibit a similar lack of nonlinear feedback control. These three lines of evidence support the hypothesis championed by Goldberger et al. [Goldberger, A.L., Rigney, D.R. & West, B.J. (1990) Sci. Am. 262, 43-49] that autonomic nervous system control underlies the nonlinearity and possible chaos of normal heart rhythms. This report demonstrates the acquisition of nonlinear heart rate dynamics and possible chaos in developing human infants and its loss in brain death and with the administration of atropine. It parallels earlier work documenting changes in the variability of heart rhythms in each of these cases and suggests that nonlinearity may provide additional power in characterizing physiological states.

The rate constant of photoinhibition, measured in lincomycin-treated leaves, is directly proportional to light intensity.

Pumpkin leaves grown under high light (500-700 micromol of photons m-2.s-1) were illuminated under photon flux densities ranging from 6.5 to 1500 micromol.m-2.s-1 in the presence of lincomycin, an inhibitor of chloroplast protein synthesis. The illumination at all light intensities caused photoinhibition, measured as a decrease in the ratio of variable to maximum fluorescence. Loss of photosystem II (PSII) electron transfer activity correlated with the decrease in the fluorescence ratio. The rate constant of photoinhibition, determined from first-order fits, was directly proportional to photon flux density at all light intensities studied. The fluorescence ratio did not decrease if the leaves were illuminated in low light in the absence of lincomycin or incubated in darkness in the presence of lincomycin. The constancy of the quantum yield of photoinhibition under different photon flux densities strongly suggests that photoinhibition in vivo occurs by one dominant mechanism under all light intensities. This mechanism probably is not the acceptor side mechanism characterized in the anaerobic case in vitro. Furthermore, there was an excellent correlation between the loss of PSII activity and the loss of the D1 protein from thylakoid membranes under low light. At low light, photoinhibition occurs so slowly that inactive PSII centers with the D1 protein waiting to be degraded do not accumulate. The kinetic agreement between D1 protein degradation and the inactivation of PSII indicates that the turnover of the D1 protein depends on photoinhibition under both low and high light.

Reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to a supraphysiologic glucose concentration is associated with loss of STF-1 transcription factor expression.

Chronic exposure of HIT-T15 beta cells to elevated glucose concentrations leads to decreased insulin gene transcription. The reduction in expression is accompanied by diminished binding of a glucose-sensitive transcription factor (termed GSTF) that interacts with two (A+T)-rich elements within the 5' flanking control region of the insulin gene. In this study we examined whether GSTF corresponds to the recently cloned insulin gene transcription factor STF-1, a homeodomain protein whose expression is restricted to the nucleus of endodermal cells of the duodenum and pancreas. We found that an affinity-purified antibody recognizing STF-1 supershifted the GSTF activator complex formed from HIT-T15 extracts. In addition, we demonstrated a reduction in STF-1 mRNA and protein levels that closely correlated with the change in GSTF binding in HIT-T15 cells chronically cultured under supraphysiologic glucose concentrations. The reduction in STF-1 expression in these cells could be accounted for by a change in the rate of STF-1 gene transcription, suggesting a posttranscriptional control mechanism. In support of this hypothesis, no STF-1 mRNA accumulated in HIT-T15 cells passaged in 11.1 mM glucose. The only RNA species detected was a 6.4-kb STF-1 RNA species that hybridized with 5' and 3' STF-1-specific cDNA probes. We suggest that the 6.4-kb RNA represents an STF-1 mRNA precursor and that splicing of this RNA is defective in these cells. Overall, this study suggests that reduced expression of a key transcriptional regulatory factor, STF-1, contributes to the decrease in insulin gene transcription in HIT-T15 cells chronically cultured in supraphysiologic glucose concentration.