A Data Mining Project to Identify Cardiovascular Related Factors That May Contribute to Changes in Visual Acuity Within the US Astronaut Corps

Many of the cardiovascular-related adaptations that occur in the microgravity environment are due, in part, to a well-characterized cephalad-fluid shift that is evidenced by facial edema and decreased lower limb circumference. It is believed that most of these alterations occur as a compensatory response necessary to maintain a "normal" blood pressure and cardiac output while in space. However, data from both flight and analog research suggest that in some instances these microgravity-induced alterations may contribute to cardiovascular-related pathologies. Most concerning is the potential relation between the vision disturbances experienced by some long duration crewmembers and changes in cerebral blood flow and intra-ocular pressure. The purpose of this project was to identify cardiovascular measures that may potentially distinguish individuals at risk for visual disturbances after long duration space flight. Toward this goal, we constructed a dataset from Medical Operation tilt/stand test evaluations pre- (days L-15-L-5) and immediate post-flight (day R+0) on 20 (3 females, 17 males). We restricted our evaluation to only crewmembers who participated in both shuttle and space station missions. Data analysis was performed using both descriptive and analytical methods (Stata 11.2, College Station, TX) and are presented as means +/- 95% CI. Crewmembers averaged 5207 (3447 - 8934) flight hours across both long (MIR-23 through Expedition16) and short (STS-27 through STS-101) duration missions between 1988 and 2008. The mean age of the crew at the time of their most recent shuttle flight was 41 (34-44) compared to 47 (40-54) years during their time on station. In order to focus our analysis (we did not have codes to separate out subjects by symptomotology) , we performed a visual inspection of each cardiovascular measures captured during testing and plotted them against stand time, pre- to post-flight, and between mission duration. It was found that pulse pressure most clearly differentiated the two mission types. Statistical analysis confirmed that pulse pressure was significantly higher before [45.6; (42.1 to 49.1)] and after [50.7; (46.9 to 54.6)] time on station compared with their most recent shuttle flight [31.6 (27.8 to 35.4), and 32.2 (28.3 to 36.0) respectively] even after correcting differences in age and cumulative number of mission hours. Without knowing the identity of which long duration crewmembers demonstrated visual changes, we were limited to examining whether certain crew regulate components of pulse pressure, systolic and diastolic blood pressure, differently due to microgravity exposure. To that end, we stratified crew into tertiles based on either their pre-flight measure of systolic or diastolic blood pressure. Those crew in the highest tertile for both systolic (lower tertile (n=8; 103-111), middle tertile (n=7; 113-121), and upper tertile (n=5; 125-136) and diastolic blood pressure (lower tertile (n=8; 58-64), middle tertile (n=7; 67-73), and upper tertile (n=5; 75-81) demonstrated less variability in pulse pressure between R+0 and L-10 (Figure 2). Interestingly, those crewmembers with the highest resting systolic blood pressure demonstrated either no change or in some instances an increase in total peripheral resistance, where those in the lower tertiles had lower values of total peripheral resistance compared to pre-flight levels. In this study, it was found that crewmembers in the highest tertile for both systolic and diastolic blood pressure demonstrated less variability in pulse pressure and that the decrease in variability was due in part to lower levels of compliance as indicated by similar or higher levels of total peripheral resistance after compared with before flight levels. Whether there is a relation between blood pressure regulation and total peripheral resistance in crew presenting with negative changes in visual acuity remains unknown

976-14 Immediate Heart Rate Response to Orthostatic Stress During β-blocker Therapy for Vasodepressor Syncope

Although β-blockers are preferred agents for therapy of vasodepressor syncope (VDS), they are not uniformly effective and their mechanism of action is incompletely understood. Since we have previously shown a differential therapeutic response to β-blocker therapy between pts with isoproterenol-independent [iso(-)] and isoproterenol-dependent [iso(+)] VDS during tilt table testing we sought to determine whether this was due to a differential heart rate (HR) response to orthostasis during β-blockade. We therefore examined immediate HR and blood pressure responses to upright tilt before and after initiation of therapy with atenolol (12.5–50mg daily) in 62 pts with VDS and positive tilt tests. The protocol comprised upright tilt (60°) for up to 60min followed by repeat tilt for 15min during isoproterenol (iso) infusion. Supine HR, mean arterial pressure (MAP) and pulse pressure (PP) were determined as the mean of 3 consecutive 1-min samples during supine rest; orthostatic HR, MAP, and PP were the mean of the samples recorded in the first 3min after upright tilt (before infusion of iso). Response to atenolol required completion of tilt with and without infusion of iso. There were 15 iso(-) pts and 47 iso(+) pts. The groups did not differ significantly in blood pressure response (MAP, PP) to orthostasis. Supine HR fell and the ΔHR in response to orthostasis was blunted during therapy in both groups:Baseline (Mean ± SD)Rx (Mean ± SD)Iso(+)Iso(-)pIso(+)Iso(-)pSupine HR69±1368±9NS57±958±8NSOrthostatic ΔHR8±712±9NS3±53±4NS11 iso(-) pts (73%) had a therapeutic response to β-blockade compared with 46 iso(+) pts (98%, p=0.01); the orthostatic ΔHR in the iso(-) pts who failed β-blocker therapy was no different from the response in the patients with a therapeutic response.ConclusionsThe HR response to orthostasis is comparably blunted after β-blockade in pts with iso(-) and iso(+) VDS, indicating that failure to respond is not due to inadequate β-blockade and suggests that in some pts iso-independent VDS may be independent of a cardiac β1 receptor mediated mechanism

Scale-dependent Associations among Fish Predation, Littoral Habitat, and Distributions of Crayfish Species

To predict how species establish and disperse within novel communities, the spatial scale at which competition, predation, and habitat interact must be understood. We explored how these factors affect the distribution and abundance of the exotic crayfishes Orconectes rusticus and O. propinquus and the native O. virilis at both the site-specific and whole-lake scales in northern Wisconsin lakes. During summer 1990, we quantified crayfish, fish predators, and fish diets in cobble and macrophyte sites in Trout Lake, comparing resulting patterns to those in 21 lakes surveyed during summer 1987. Within and across lakes, fish abundance was unrelated to habitat. Within Trout Lake, O. rusticus and O. propinquus were common in both cobble and macrophyte. Orconectes virilis was restricted to macrophyte, probably due to strong displacement by the invaders in cobble. Across lakes, O. rusticus increased where habitat was more than 16.7% cobble, O. propinquus was generally rare, and O. virilis abundance was unrelated to cobble. Crayfish were generally small in cobble and large in macrophyte, perhaps because of habitat-specific, size-selective fish predation or because large crayfish leave cobble when it no longer provides refuge. Orconectes virilis, the largest of three congeners, may have a size refuge in macrophyte but not in cobble. Across lakes, O. rusticus was only abundant when fish biomass was low; O. virilis abundance varied positively with fish. Effects of fish predation and habitat on the ability of invaders Orconectes rusticus and O. propinquus to establish and replace O. virilis appear to be scale dependent. At local (site-specific) scales, cobble likely interacts with selective predation for O. virilis to allow the invaders to establish and replace the native. At the lake-wide scale, high cobble facilitates invaders but predation may curb their successful dispersal and establishment at new sites. Models of community assembly and invasions need to incorporate scale dependencies in habitat availability and biotic interactions to effectively assess the invasion potential of novel species

Text-mining assisted regulatory annotation

Text-mining technologies can be integrated with genome annotation systems, increasing the availability of annotated cis-regulatory data

Modification of Thermal Emission via Metallic Photonic Crystals

Photonic crystals are materials that are periodically structured on an optical length scale. It was previously demonstrated that the glow, or thermal emission, of tungsten photonic crystals that have a specific structure - known as the 'woodpile structure' - could be modified to reduce the amount of infrared radiation from the material. This ability has implications for improving the efficiency of thermal emission sources and for thermophotovoltaic devices. The study of this effect had been limited because the fabrication of metallic woodpile structures had previously required a complex fabrication process. In this project we pursued several approaches to simplify the fabrication of metallic photonic crystals that are useful for modification of thermal emission. First, we used the self-assembly of micrometer-scale spheres into colloidal crystals known as synthetic opals. These opals can then be infiltrated with a metal and the spheres removed to obtain a structure, known as an inverse opal, in which a three-dimensional array of bubbles is embedded in a film. Second, we used direct laser writing, in which the focus of an infrared laser is moved through a thin film of photoresist to form lines by multiphoton polymerization. Proper layering of such lines can lead to a scaffold with the woodpile structure, which can be coated with a refractory metal. Third, we explored a completely new approach to modified thermal emission - thin metal foils that contain a simple periodic surface pattern, as shown in Fig. 1. When such a foil is heated, surface plasmons are excited that propagate along the metal interface. If these waves strike the pattern, they can be converted into thermal emission with specific properties

Modification of Thermal Emission via Metallic Photonic Crystals

Photonic crystals are materials that are periodically structured on an optical length scale. It was previously demonstrated that the glow, or thermal emission, of tungsten photonic crystals that have a specific structure - known as the 'woodpile structure' - could be modified to reduce the amount of infrared radiation from the material. This ability has implications for improving the efficiency of thermal emission sources and for thermophotovoltaic devices. The study of this effect had been limited because the fabrication of metallic woodpile structures had previously required a complex fabrication process. In this project we pursued several approaches to simplify the fabrication of metallic photonic crystals that are useful for modification of thermal emission. First, we used the self-assembly of micrometer-scale spheres into colloidal crystals known as synthetic opals. These opals can then be infiltrated with a metal and the spheres removed to obtain a structure, known as an inverse opal, in which a three-dimensional array of bubbles is embedded in a film. Second, we used direct laser writing, in which the focus of an infrared laser is moved through a thin film of photoresist to form lines by multiphoton polymerization. Proper layering of such lines can lead to a scaffold with the woodpile structure, which can be coated with a refractory metal. Third, we explored a completely new approach to modified thermal emission - thin metal foils that contain a simple periodic surface pattern, as shown in Fig. 1. When such a foil is heated, surface plasmons are excited that propagate along the metal interface. If these waves strike the pattern, they can be converted into thermal emission with specific properties

Exome sequencing identifies nonsegregating nonsense ATM and PALB2 variants in familial pancreatic cancer.

We sequenced 11 germline exomes from five families with familial pancreatic cancer (FPC). One proband had a germline nonsense variant in ATM with somatic loss of the variant allele. Another proband had a nonsense variant in PALB2 with somatic loss of the variant allele. Both variants were absent in a relative with FPC. These findings question the causal mechanisms of ATM and PALB2 in these families and highlight challenges in identifying the causes of familial cancer syndromes using exome sequencing

Predicting impact of freshwater exotic species on native biodiversity: Challenges in spatial scaling

Global homogenization of biota is underway through worldwide introduction and establishment of nonindigenous (exotic) species. Freshwater ecologists should devote more attention to exotic species for two reasons. First, exotics provide an opportunity to test hypotheses about what characteristics of species or habitats are related to successful establishment or invasibility, respectively. Second, predicting which species will cause large ecological change is an important challenge for natural resource managers. Rigorous statistical relationships linking species characteristics to probability of establishment or of causing ecological impacts are needed. In addition, it is important to know how reliable different sorts of experiments are in guiding predictions. We address this issue with different spatial scales of experiments testing the impact of two predators on native snail assemblages in northern Wisconsin USA lakes: an exotic crayfish, the rusty crayfish (Orconectes rusticus); and a native fish predator, the pumpkinseed sunfish (Lepomis gibossus). For the crayfish, laboratory experiments, a field cage experiment, and a snapshot survey of 21 lakes gave consistent results: the crayfish reduced abundance and species richness of native snails. Laboratory and field experiments suggested that pumpkinseed sunfish should have a similar impact, but the lake survey suggested little impact. Unfortunately, no algorithms exist to guide scaling up from small-scale experiments to the whole-lake, long-term management scale. To protect native biodiversity, management of freshwater exotic species should be targeted on lakes or drainages that are both vulnerable to colonization by an exotic, and that harbour endemic species. Management should focus on preventing introduction because eradication after establishment is usually not possible.The following grants funded our research: NSFBSR85-00775, NSFBSR89-07407, EPA CR820290-0T -0 (to DML)

Pervasive gene content variation and copy number variation in maize and its undomesticated progenitor

Individuals of the same species are generally thought to have very similar genomes. However, there is growing evidence that structural variation in the form of copy number variation (CNV) and presence-absence variation (PAV) can lead to variation in the genome content of individuals within a species. Array comparative genomic hybridization (CGH) was used to compare gene content and copy number variation among 19 diverse maize inbreds and 14 genotypes of the wild ancestor of maize, teosinte. We identified 479 genes exhibiting higher copy number in some genotypes (UpCNV) and 3410 genes that have either fewer copies or are missing in the genome of at least one genotype relative to B73 (DownCNV/PAV). Many of these DownCNV/PAV are examples of genes present in B73, but missing from other genotypes. Over 70% of the CNV/PAV examples are identified in multiple genotypes, and the majority of events are observed in both maize and teosinte, suggesting that these variants predate domestication and that there is not strong selection acting against them. Many of the genes affected by CNV/PAV are either maize specific (thus possible annotation artifacts) or members of large gene families, suggesting that the gene loss can be tolerated through buffering by redundant functions encoded elsewhere in the genome. While this structural variation may not result in major qualitative variation due to genetic buffering, it may significantly contribute to quantitative variation