Engine panel seals for hypersonic engine applications: High temperature leakage assessments and flow modelling

A critical mechanical system in advanced hypersonic engines is the panel-edge seal system that seals gaps between the articulating horizontal engine panels and the adjacent engine splitter walls. Significant advancements in seal technology are required to meet the extreme demands placed on the seals, including the simultaneous requirements of low leakage, conformable, high temperature, high pressure, sliding operation. In this investigation, the seal concept design and development of two new seal classes that show promise of meeting these demands will be presented. These seals include the ceramic wafer seal and the braided ceramic rope seal. Presented are key elements of leakage flow models for each of these seal types. Flow models such as these help designers to predict performance-robbing parasitic losses past the seals, and estimate purge coolant flow rates. Comparisons are made between measured and predicted leakage rates over a wide range of engine simulated temperatures and pressures, showing good agreement

Fish oil (n-3 fatty acids) in drug resistant epilepsy: a randomised placebo-controlled crossover study.

Backgroundn-3 fatty acids inhibit neuronal excitability and reduce seizures in animal models. High-dose fish oil has been explored in two randomised trials in drug resistant epilepsy with negative results. We performed a phase II randomised controlled crossover trial of low-dose and high-dose fish oil in participants with drug resistant epilepsy to explore whether low-dose or high-dose fish oil reduces seizures or improves cardiovascular health.MethodsRandomised placebo-controlled trial of low-dose and high-dose fish oil versus placebo (corn oil, linoleic acid) in 24 participants with drug resistant epilepsy. A three-period crossover design was utilised lasting 42 weeks, with three 10-week treatment periods and two 6-week washout periods. All participants were randomised in double-blind fashion to receive placebo, high dose or low dose in different sequences. The primary outcome was per cent change in total seizure frequency.FindingsLow-dose fish oil (3 capsules/day, 1080 mg eicosapentaenoic acid+docosahexaenoic acid) was associated with a 33.6% reduction in seizure frequency compared with placebo. Low-dose fish oil was also associated with a mild but significant reduction in blood pressure. High-dose fish oil was no different than placebo in reducing seizures or improving cardiac risk factors.InterpretationIn this phase II randomised crossover trial, low-dose fish oil was effective in reducing seizures compared with placebo. The magnitude of improvement is similar to that of recent antiepileptic drug trials in drug resistant epilepsy (DRE). The results indicate that low-dose fish oil may reduce seizures and improve the health of people with epilepsy. These findings justify a large multicentre randomised trial of low-dose fish oil (n-3 fatty acids <1080 mg/day) in drug resistant epilepsy.Trial registration numberNCT00871377

Marine Archeological Survey of the Proposed Bolivar Ferry Dredge Spoil Pile Expansion Area, Galveston County, Texas

Archeologists from AmaTerra Environmental, Inc. (AmaTerra) and Southeastern Archaeological Research, Inc. (SEARCH; collectively the Team) conducted intensive underwater archeological remote sensing survey on behalf of the Texas Department of Transportation (TxDOT) on a proposed dredge spoil expansion area south of the Bolivar Peninsula at the mouth of Galveston Bay, Galveston County, Texas. The survey was required for compliance with the National Historic Preservation Act of 1966, as amended, due to dredge permits to be issued by the US Fish and Wildlife Service, and the Antiquities Code of Texas, due to its location on lands owned by a political subdivision of the State of Texas (the Texas General Land Office). Completed under Antiquities Permit 6272, the survey area includes the 51-acre dredge spoil expansion footprint and the original 16-acre dredge spoil pile (67 acres total). The archeologists utilized towed marine magnetometer and side-scan sonar survey along 12 parallel, 20-meter-interval transects to assess the full archeological Area of Potential Effects. The survey area was found to be littered with isolated modern metallic debris. Side-scan sonar imagery revealed a submerged surface that was generally flat with no indications of shipwrecks and a large oyster reef along the southwestern quarter. One large metallic feature located within the survey area (Anomaly M1) was identified as a fallen modern navigational sighting marker tower. None of the archeological survey data, sensor readings, or imagery from the proposed expansion area is consistent with expected signatures of historic-age shipwrecks. Archeologists did re-identify the previously-documented magnetic anomaly M44 that was recommended for avoidance or testing within the original dredge pile area. If the avoidance zone continues to be observed, it will not be impacted by the current undertaking. As such, the project is recommended to proceed with no Historic Properties, State Archeological Landmarks, or archeological sites impacted in accordance with guidelines outlined in 36 CFR 800 and 13 TAC 26. No sites were identified and no artifacts were collected during the course of the survey. Accordingly, all project-generated notes, forms, and other materials will be permanently curated at AmaTerra’s office in Austin, Texas and SEARCH’s office in Pensacola, Florida

Phosphatidylinositol 3-kinase pathway genomic alterations in 60,991 diverse solid tumors informs targeted therapy opportunities.

BackgroundThe phosphatidylinositol 3-kinase (PI3K) pathway is frequently altered in cancer. This report describes the landscape of PI3K alterations in solid tumors as well as co-alterations serving as potential resistance/attenuation mechanisms.MethodsConsecutive samples were analyzed in a commercial Clinical Laboratory Improvement Amendment-certified laboratory using comprehensive genomic profiling performed by next-generation sequencing (315 genes). The co-alterations evaluated included the Erb-B2 receptor tyrosine kinase 2 (ERBB2), ERBB3, ERBB4, RAS, MET proto-oncogene tyrosine kinase (MET), and mitogen-activated protein kinase kinase (MAP2K) genes as well as tumor protein 53 (TP53), estrogen receptor 1 (ESR1), and androgen receptor (AR).ResultsAlterations in any of 18 PI3K-pathway associated genes were identified in 44% of 60,991 tumors. Although single base and insertions/deletions (indels) were the most frequent alterations, copy number changes and rearrangements were identified in 11% and 0.9% of patients, respectively. Overall, the most frequently altered genes were PIK3 catalytic subunit α (PIK3CA) (13%), phosphatase and tensin homolog (PTEN) (9%), and serine/threonine kinase 11 (STK11) (5%). Tumor types that frequently harbored at least 1 PI3K alteration were uterine (77%), cervical (62%), anal (59%), and breast (58%) cancers. Alterations also were discerned frequently in tumors with carcinosarcoma (89%) and squamous cell carcinoma (62%) histologies. Tumors with a greater likelihood of co-occurring PI3K pathway and MAPK pathway alterations included colorectal cancers (odds ratio [OR], 1.64; P < .001), mesotheliomas (OR, 2.67; P = .024), anal cancers (OR, 1.98; P = .03), and nonsquamous head and neck cancers (OR, 2.03; P = .019). The co-occurrence of ESR1 and/or AR alterations with PI3K alterations was statistically significant in bladder, colorectal, uterine, prostate, and unknown primary cancers.ConclusionsComprehensive genomic profiling reveals altered PI3K-related genes in 44% of solid malignancies, including rare disease and histology types. The frequency of alterations and the co-occurrence of resistance pathways vary by tumor type, directly affecting opportunities for targeted therapy

Carbon isotope discrimination by Eucalyptus species in the Northern Territory, Australia

Carbon isotope discrimination (Δ) reflects the balance between the supply of C0₂ into the intercellular airspaces of a leaf and the demand of photosynthesis for C0₂ from those intercellular airspaces. The conductance of C0₂ into a leaf depends upon the plant being able to sustain the co-occurring transpiration, which requires the acquisition and transport of water at rates equal to the evaporative demand. The photosynthetic demand for C0₂ depends upon the investment of nutrients, primarily nitrogen, in photosynthetic enzymes. Plants with high conductance, relative to photosynthetic capacity, will have little reduction in intercellular C0₂ concentrations relative to the ambient source C0₂ concentration outside the leaf, and therefore high Δ values. Plants with either low conductances or high photosynthetic capacities will have low intercellular C0₂ concentrations and low Δ values, reflecting a high degree of stomatal limitation on photosynthesis. Carbon isotope discrimination therefore reflects the balance between the water and nutrient economies of plants, and when combined with information on the distribution of a species may yield insight into the success of the genetically determined growth strategy for the uptake and utilization of these resources. From Darwin, on the north coast of Australia, to the southern border of the Northern Territory there is an eight-fold decrease in total annual rainfall with little topographic complexity. A transect across this gradient includes plant communities in the wetter northern areas that are dominated by Eucalyptus species, while the arid southern areas are dominated by potentially N-fixing Acacia species. This broad-scale replacement of a possibly high water-using growth strategy by a high nitrogen-using strategy along a gradient of decreasing water availability would seem ideal for study using carbon isotope discrimination. This is especially true since carbon isotope discrimination records a production-weighted measure of the ability of conductance to supply C0₂ for photosynthesis over time periods approximating the duration of the time required for the growth of the sampled tissue. The carbon isotope discrimination recorded in wood tissue would presumably record conditions over a full year in an annual growth increment, with conditions over many years being integrated by combining the growth during multiple years. Although carbon isotope discrimination is a leaf-level phenomenon, it has been used as a successful surrogate measure of the water-use efficiency of co-occurring whole plants. Where the evaporative demands are the same, i.e. plants have similar leaf temperatures and therefore similar leaf-to-air vapor pressure deficits, and are not competing for the same limited water supply, slow rates of water-use (and necessarily limited rates of carbon gain) are more efficient, and will result in greater final biomass accumulation, than high rates of water use, assuming similar allocation patterns for reinvesting photosynthate towards resource acquisition. Low rates of water-use, and a high degree of stomatal limitation on C0₂ supply for photosynthesis will result in low Δ values correlating with this high biomass production. When any of those pre-conditions is not completely satisfied, arguments can be made that the plant with lower stomatal limitation on photosynthesis should be a better performer. The ambiguity of the potential response of Δ to decreasing water availability in naturally occurring plant populations is work. Carbon isotope discrimination was measured in leaf and wood tissue across the distributions of a series of co-occurring and replacement species along a rainfall gradient. With decreasing rainfall, the whole-tissue leaf Δ of five of 13 species decreased, seven exhibited no trend, and one increased. The whole-tissue wood Δ of eight species decreased, showed no trend in four species, and increased in one species. Species replacements were marked by a shift in Δ reflecting greater stomatal limitation on assimilation. There was a non-linear response of the multi-species average leaf and wood Δ to decreasing total annual rainfall. This response reflected the spatial pattern of the sensitivities of Δ to decreasing rainfall of the individual species and was not the result of a proposed emergent behavior where the mean would differ from the responses of the individual species. Because the patterns in Δ in response to decreasing water availability were not common to all species it was not possible to determine the extent to which Δ is a measure of the stomatal limitation on photosynthesis, i.e. is a measure of the reaction to environmental stress. The patterns of Δ across the distributions of the species did not provide a simple measure of the physiological limits of the distribution of eucalypts in northwestern Australia. As Δ measures the ratio of leaf conductance to assimilation capacity, movement in either factor could generate a signal, while combined movement could result in no signal. Although the opportunity to directly measure the magnitude of leaf conductance and assimilation capacity in a subset of the sampling locations would have greatly assisted in the understanding of their dynamics across the transect and the patterns in Δ, assimilation capacity had to be estimated from leaf nitrogen contents. The increase in area-based leaf nitrogen contents is explored in Chapter 4. The uptake of C0₂ can be viewed as a two-step process, the first involving C0₂ entering the leaf and stomatal conductance and the second involving the actual _photosynthetic uptake from the intercellular airspace depending on leaf nitrogen contents and investment in photosynthetic enzymes. The two processes are in series such that a decrease in either could be offset by an increase in the other to maintain the overall photosynthetic rate. This principle of resource substitution is a basic idea of economics and there is a well developed mathematical treatment of the issue coming from the fields of consumer behavior and the production of firms. Such concepts as the intrinsic antagonism of water-use efficiency (the rate of carbon gain per unit water lost in transpiration) and nitrogen-use efficiency (the rate of carbon gain per unit nitrogen lost in leaf senescence) are obvious outcomes of resource substitution. The mathematics of resource substitution and related concepts as applicable to a simple model of photosynthesis, transpiration, and root investment for acquiring water and nitrogen is developed in Chapter 4. The measured increases in leaf nitrogen contents were estimated to account for between 50 and 75% of the projected change in water-use as water availability decreased across the transect. The increasing leaf nitrogen contents with decreasing rainfall across the transect were predicted to result in increased photosynthetic capacities. As water availability decreased there was also an increase in the leaf-mass per unit area and the leaf-carbon content per unit area. This increased investment of carbon in leaves was presumed to be a mechanism to withstand low water potentials and would result in longer periods to recover the costs of the leaves. From the calculated gas exchange rates (based on leaf nitrogen contents and leaf Δ) the patterns in the leaf payback period are predicted in Chapter 5. The predicted increases in photosynthetic capacities as a result of increases in leaf nitrogen contents were not large enough to balance the increases in leaf carbon contents, and all but one species was predicted to have increasing leaf payback periods with decreasing rainfall across their distribution. This increase in the time required to recover the cost of the leaves, combined with a predicted decrease in the maximum supportable leaf area index could indicate the physiological limits to the distribution of each species. The environmental influences of decreasing water supply and increasing evaporative demand on leaf conductance are relatively well understood from experiments in controlled conditions (see Chapter 6). The link between leaf nitrogen contents and photosynthetic capacity, and then the theory relating Δ to leaf conductance and assimilation capacity are also well understood. The extent to which these links could be found in the 1300 measurements of leaf or wood Δ is explored in Chapter 6. Long-term predicted mean meteorological conditions did not explain the patterns or variability in leaf or wood Δ in a satisfying manner. The rainfall in the Northern Territory is strongly seasonal, so that the gradient in annual rainfall masks the fact that all along the transect there is a dry season with little or no rainfall for around three months or longer. The mean interval between rain events, or drought length, was often as important as rainfall in explaining patterns of b.. This could indicate that selection has tuned the rate of water-use to match the time period between supply events. The degree to which the trees of the Northern Territory are able to tap a reliable ground-water supply by increasing their allocation to root growth, and the degree to which they operate with partially open stomata (which would generate a low D. signal) rather than merely operating in an open or shut mode (with would avoid recording a low D. signal as there would be no concurrent assimilation) were beyond the scope of Chapter 7 which addressed the ability of the species to change their physiological and morphological characteristics across their distributions. Plasticity would allow a species to adjust to varying conditions, but is thought to be a risky behavior under the most extreme conditions when genetically controlled conservative behavior is often observed. Variability within populations may also decrease with increasing stress levels where only a limited sub-population of growth strategies remain viable. Physiological parameters, specifically wood and leaf Δ, had lower elasticities than the measured morphological parameters, emphasizing that subtle changes in Δ are of potentially great importance as indicators of plant performance. Although carbon isotope discrimination should have allowed a quick and efficient method for broadly establishing the potential ecophysiological controls on the distributions of Eucalyptus species in the Northern Territory, to be followed upon by direct measures of gas exchange parameters, the realities of the method preclude its viability in the limited duration of a PhD thesis. No single measure conducted in a laboratory thousands of kilometers from the field can compensate for a lack of direct field experience

Rescuing tomorrow today: fixing training and development for DHS leaders

Leadership is an essential quality that all homeland security professionals should possess. Unfortunately, the nature, scope, importance, and complexity of protecting the United States has overshadowed the fact that Department of Homeland Security (DHS) employees are not receiving the proper leadership training. Furthermore, lack of adequate training tools within the department is making it increasingly difficult to deliver the limited amount of available leadership training education. Personnel surveys reveal that the quality of leadership within the department is not getting better, and in some cases, it is perceived as worsening. As the first generation of homeland security leaders and managers depart the organization, DHS has a responsibility to its future generation of employees to identify leadership training and education deficiencies and provide individuals with the proper leadership tools for individual and departmental success. This thesis proposes that senior DHS leaders admit to the leadership training deficiencies, create programs to fill leadership training gaps in an integrated manner throughout the organization, develop accountability measures, and utilize portions of effective training and development programs from Department of Defense and civilian corporations alike.http://archive.org/details/rescuingtomorrow1094550595Lieutenant, United States NavyApproved for public release; distribution is unlimited

Database management and analysis of fisheries in Illinois: Final report, 1 March 1999-28 February 2002

Issued May 2002; F-69-RReport issued on: May 200

Impacts of Drying and Rewetting on the Radiocarbon Signature of Respired CO2 and Implications for Incubating Archived Soils

The radiocarbon signature of respired CO2 (∆14C-CO2) measured in laboratory soil incubations integrates contributions from soil carbon pools with a wide range of ages, making it a powerful model constraint. Incubating archived soils enriched by “bomb-C” from mid-20th century nuclear weapons testing would be even more powerful as it would enable us to trace this pulse over time. However, air-drying and subsequent rewetting of archived soils, as well as storage duration, may alter the relative contribution to respiration from soil carbon pools with different cycling rates. We designed three experiments to assess air-drying and rewetting effects on ∆14C-CO2 with constant storage duration (Experiment 1), without storage (Experiment 2), and with variable storage duration (Experiment 3). We found that air-drying and rewetting led to small but significant (α < 0.05) shifts in ∆14C-CO2 relative to undried controls in all experiments, with grassland soils responding more strongly than forest soils. Storage duration (4–14 y) did not have a substantial effect. Mean differences (95% CIs) for experiments 1, 2, and 3 were: 23.3‰ (±6.6), 19.6‰ (±10.3), and 29.3‰ (±29.1) for grassland soils, versus −11.6‰ (±4.1), 12.7‰ (±8.5), and −24.2‰ (±13.2) for forest soils. Our results indicate that air-drying and rewetting soils mobilizes a slightly older pool of carbon that would otherwise be inaccessible to microbes, an effect that persists throughout the incubation. However, as the bias in ∆14C-CO2 from air-drying and rewetting is small, measuring ∆14C-CO2 in incubations of archived soils appears to be a promising technique for constraining soil carbon models

Novel pathogenic variants in filamin C identified in pediatric restrictive cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare and distinct form of cardiomyopathy characterized by normal ventricular chamber dimensions, normal myocardial wall thickness, and preserved systolic function. The abnormal myocardium, however, demonstrates impaired relaxation. To date, dominant variants causing RCM have been reported in a small number of sarcomeric or cytoskeletal genes, but the genetic causes in a majority of cases remain unexplained, especially in early childhood. Here, we describe two RCM families with childhood onset: one in a large family with a history of autosomal dominant RCM and the other a family with affected monozygotic, dichorionic/diamniotic twins. Exome sequencing found a pathogenic filamin C (FLNC) variant in each: p.Pro2298Leu, which segregates with disease in the large autosomal dominant RCM family, and p.Tyr2563Cys in both affected twins. In vitro expression of both mutant proteins yielded aggregates of FLNC containing actin in C2C12 myoblast cells. Recently, a number of variants in FLNC have been described that cause hypertrophic, dilated, and restrictive cardiomyopathies. Our data presented here provide further evidence for the role of FLNC in pediatric RCM, and suggest the need to include FLNC in genetic testing of cardiomyopathy patients including those with early ages of onset