Maxent Estimation of Aquatic Escherichia Coli Stream Impairment

Background.The leading cause of surface water impairment in United States’ rivers and streams is pathogen contamination. Although use of fecal indicators has reduced human health risk, current approaches to identify and reduce exposure can be improved. One important knowledge gap within exposure assessment is characterization of complex fate and transport processes of fecal pollution. Novel modeling processes can inform watershed decision-making to improve exposure assessment

Molecular pathways and therapeutic targets in lung cancer

Lung cancer is still the leading cause of cancer death worldwide. Both histologically and molecularly lung cancer is heterogeneous. This review summarizes the current knowledge of the pathways involved in the various types of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. It describes the major pathways and molecular alterations implicated in the development and progression of non-small cell lung cancer (adenocarcinoma and squamous cancer), and of small cell carcinoma, emphasizing the molecular alterations comprising the specific blueprints in each group. The approved and investigational targeted therapies as well as the immune therapies, and clinical trials exploring the variety of targeted approaches to treatment of lung cancer are the main focus of this review

Pulse-echo ultrasonic inspection system for in-situ nondestructive inspection of Space Shuttle RCC heat shields.

The reinforced carbon-carbon (RCC) heat shield components on the Space Shuttle's wings must withstand harsh atmospheric reentry environments where the wing leading edge can reach temperatures of 3,000 F. Potential damage includes impact damage, micro cracks, oxidation in the silicon carbide-to-carbon-carbon layers, and interlaminar disbonds. Since accumulated damage in the thick, carbon-carbon and silicon-carbide layers of the heat shields can lead to catastrophic failure of the Shuttle's heat protection system, it was essential for NASA to institute an accurate health monitoring program. NASA's goal was to obtain turnkey inspection systems that could certify the integrity of the Shuttle heat shields prior to each mission. Because of the possibility of damaging the heat shields during removal, the NDI devices must be deployed without removing the leading edge panels from the wing. Recently, NASA selected a multi-method approach for inspecting the wing leading edge which includes eddy current, thermography, and ultrasonics. The complementary superposition of these three inspection techniques produces a rigorous Orbiter certification process that can reliably detect the array of flaws expected in the Shuttle's heat shields. Sandia Labs produced an in-situ ultrasonic inspection method while NASA Langley developed the eddy current and thermographic techniques. An extensive validation process, including blind inspections monitored by NASA officials, demonstrated the ability of these inspection systems to meet the accuracy, sensitivity, and reliability requirements. This report presents the ultrasonic NDI development process and the final hardware configuration. The work included the use of flight hardware and scrap heat shield panels to discover and overcome the obstacles associated with damage detection in the RCC material. Optimum combinations of custom ultrasonic probes and data analyses were merged with the inspection procedures needed to properly survey the heat shield panels. System features were introduced to minimize the potential for human factors errors in identifying and locating the flaws. The in-situ NDI team completed the transfer of this technology to NASA and USA employees so that they can complete 'Return-to-Flight' certification inspections on all Shuttle Orbiters prior to each launch

Metabolomic Shifts Associated with Heat Stress in Coral Holobionts

Understanding the response of the coral holobiont to environmental change is crucial to inform conservation efforts. The most pressing problem is “coral bleaching,” usually precipitated by prolonged thermal stress. We used untargeted, polar metabolite profiling to investigate the physiological response of the coral species Montipora capitata and Pocillopora acuta to heat stress. Our goal was to identify diagnostic markers present early in the bleaching response. From the untargeted UHPLC-MS data, a variety of co-regulated dipeptides were found that have the highest differential accumulation in both species. The structures of four dipeptides were determined and showed differential accumulation in symbiotic and aposymbiotic (alga-free) populations of the sea anemone Aiptasia (Exaiptasia pallida), suggesting the deep evolutionary origins of these dipeptides and their involvement in symbiosis. These and other metabolites may be used as diagnostic markers for thermal stress in wild coral

A Lower Limit on the Mass of Our Galaxy from the H3 Survey

The timing argument provides a lower limit on the mass of the Milky Way. We find, using a sample of 32 stars at $R > 60$ kpc drawn from the H3 Spectroscopic Survey and mock catalogs created from published numerical simulations, that M$_{200} > 0.91\times 10^{12}$ M$_\odot$ with 90% confidence. We recommend using this limit to refine the allowed prior mass range in more complex and sophisticated statistical treatments of Milky Way dynamics. The use of such a prior would have significantly reduced many previously published uncertainty ranges. Our analysis suggests that the most likely value of M$_{200}$ is $\sim 1.4 \times 10^{12}$ M$_\odot$, but establishing this as the Milky Way mass requires a larger sample of outer halo stars and a more complete analysis of the inner halo stars in H3. The imminent growth in the sample of outer halo stars due to ongoing and planned surveys will make this possible.Comment: 8 pages, submitted for publicatio

Automated Low-Gravitation Facility Would Make Optical Fibers

A report describes a proposed automated facility that would be operated in outer space to produce high-quality optical fibers from fluoride-based glasses, free of light-scattering crystallites that form during production in normal Earth gravitation. Before launch, glass preforms would be loaded into a mechanism that would later dispense them. A dispensed preform would be melted, cooled to its glass-transition temperature rapidly enough to prevent crystallization, cooled to ambient temperature, then pushed into a preform tip heater, wherein it would be reheated to the softening temperature. A robotic manipulator would touch a fused silica rod to the softened glass to initiate pulling of a fiber. The robot would pull the fiber to an attachment on a take-up spool, which would thereafter be turned to pull the fiber. The diameter of the fiber would depend on the pulling speed and the viscosity of the glass at the preform tip. Upon depletion of a preform, the robot would place the filled spool in storage and position an empty spool to pull a fiber from a new preform. Pulling would be remotely monitored by a video camera and restarted by remote command if a break in the fiber were observed

Evidence from the H3 Survey that the Stellar Halo is Entirely Comprised of Substructure

In the $\Lambda$CDM paradigm the Galactic stellar halo is predicted to harbor the accreted debris of smaller systems. To identify these systems, the H3 Spectroscopic Survey, combined with $Gaia$, is gathering 6D phase-space and chemical information in the distant Galaxy. Here we present a comprehensive inventory of structure within 50 kpc from the Galactic center using a sample of 5684 giants at $|b|>40^{\circ}$ and $|Z|>2$ kpc. We identify known structures including the high-$\alpha$ disk, the in-situ halo (disk stars heated to eccentric orbits), Sagittarius (Sgr), $Gaia$-Sausage-Enceladus (GSE), the Helmi Streams, Sequoia, and Thamnos. Additionally, we identify the following new structures: (i) Aleph ([Fe/H]$=-0.5$), a low eccentricity structure that rises a surprising 10 kpc off the plane, (ii, iii) Arjuna ([Fe/H]$=-1.2$) and I'itoi ([Fe/H]$<-2$), which comprise the high-energy retrograde halo along with Sequoia, and (iv) Wukong ([Fe/H]$=-1.6$), a prograde phase-space overdensity chemically distinct from GSE. For each structure we provide [Fe/H], [$\alpha$/Fe], and orbital parameters. Stars born within the Galaxy are a major component at $|Z|\sim$2 kpc ($\approx$60$\%$), but their relative fraction declines sharply to $\lesssim$5$\%$ past 15 kpc. Beyond 15 kpc, $>$80$\%$ of the halo is built by two massive ($M_{\star}\sim10^{8}-10^{9}M_{\odot}$) accreted dwarfs: GSE ([Fe/H]$=-1.2$) within 25 kpc, and Sgr ([Fe/H]$=-1.0$) beyond 25 kpc. This explains the relatively high overall metallicity of the halo ([Fe/H]$\approx-1.2$). We attribute $\gtrsim$95$\%$ of the sample to one of the listed structures, pointing to a halo built entirely from accreted dwarfs and heating of the disk.Comment: Submitted to ApJ. Key results in Figures 18-21. Summary of individual structures in Sec. 3.3 and Table 1. Comments very welcome

Small-molecule antagonists of the oncogenic Tcf/β-catenin protein complex

AbstractKey molecular lesions in colorectal and other cancers cause β-catenin-dependent transactivation of T cell factor (Tcf)-dependent genes. Disruption of this signal represents an opportunity for rational cancer therapy. To identify compounds that inhibit association between Tcf4 and β-catenin, we screened libraries of natural compounds in a high-throughput assay for immunoenzymatic detection of the protein-protein interaction. Selected compounds disrupt Tcf/β-catenin complexes in several independent in vitro assays and potently antagonize cellular effects of β-catenin-dependent activities, including reporter gene activation, c-myc or cyclin D1 expression, cell proliferation, and duplication of the Xenopus embryonic dorsal axis. These compounds thus meet predicted criteria for disrupting Tcf/β-catenin complexes and define a general standard to establish mechanism-based activity of small molecule inhibitors of this pathogenic protein-protein interaction

Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10

Human melanoma cells frequently express CC chemokine receptor (CCR)10, a receptor whose ligand (CCL27) is constitutively produced by keratinocytes. Compared with B16 murine melanoma, cells rendered more immunogenic via overexpression of luciferase, B16 cells that overexpressed both luciferase and CCR10 resisted host immune responses and readily formed tumors. In vitro, exposure of tumor cells to CCL27 led to rapid activation of Akt, resistance to cell death induced by melanoma antigen-specific cytotoxic T cells, and phosphatidylinositol-3-kinase (PI3K)–dependent protection from apoptosis induced by Fas cross-linking. In vivo, cutaneous injection of neutralizing antibodies to endogenous CCL27 blocked growth of CCR10-expressing melanoma cells. We propose that CCR10 engagement by locally produced CCL27 allows melanoma cells to escape host immune antitumor killing mechanisms (possibly through activation of PI3K/Akt), thereby providing a means for tumor progression

A Diffuse Metal-Poor Component of the Sagittarius Stream Revealed by the H3 Survey

The tidal disruption of the Sagittarius dwarf galaxy has generated a spectacular stream of stars wrapping around the entire Galaxy. We use data from $Gaia$ and the H3 Stellar Spectroscopic Survey to identify 823 high-quality Sagittarius members based on their angular momenta. The H3 Survey is largely unbiased in metallicity, and so our sample of Sagittarius members is similarly unbiased. Stream stars span a wide range in [Fe/H] from $-0.2$ to $\approx -3.0$, with a mean overall metallicity of $\langle$[Fe/H]$\rangle=-0.99$. We identify a strong metallicity-dependence to the kinematics of the stream members. At [Fe/H]$\gt -0.8$ nearly all members belong to the well-known cold ($\sigma_v \lt 20$ km/s) leading and trailing arms. At intermediate metallicities ($-1.9 \lt$[Fe/H]$\lt -0.8$) a significant population (24$\%$) emerges of stars that are kinematically offset from the cold arms. These stars also appear to have hotter kinematics. At the lowest metallicities ([Fe/H]$\lesssim-2$), the majority of stars (69$\%$) belong to this kinematically-offset diffuse population. Comparison to simulations suggests that the diffuse component was stripped from the Sagittarius progenitor at earlier epochs, and therefore resided at larger radius on average, compared to the colder metal-rich component. We speculate that this kinematically diffuse, low metallicity, population is the stellar halo of the Sagittarius progenitor system.Comment: 18 pages, 12 figures, 1 table. Submitted to Ap