Doubting and Believing: The Hermeneutics of Suspicion in Contexts of Faith

A belief-centered pedagogy helps students infuse cultural values into adversarial modes of academic writing

Wind Fins: Novel Lower-Cost Wind Power System

This project evaluated the technical feasibility of converting energy from the wind with a novel “wind fin” approach. This patent-pending technology has three major components: (1) a mast, (2) a vertical, hinged wind structure or fin, and (3) a power takeoff system. The wing structure responds to the wind with an oscillating motion, generating power. The overall project goal was to determine the basic technical feasibility of the wind fin technology. Specific objectives were the following: (1) to determine the wind energy-conversion performance of the wind fin and the degree to which its performance could be enhanced through basic design improvements; (2) to determine how best to design the wind fin system to survive extreme winds; (3) to determine the cost-effectiveness of the best wind fin designs compared to state-of-the-art wind turbines; and (4) to develop conclusions about the overall technical feasibility of the wind fin system. Project work involved extensive computer modeling, wind-tunnel testing with small models, and testing of bench-scale models in a wind tunnel and outdoors in the wind. This project determined that the wind fin approach is technically feasible and likely to be commercially viable. Project results suggest that this new technology has the potential to harvest wind energy at approximately half the system cost of wind turbines in the 10kW range. Overall, the project demonstrated that the wind fin technology has the potential to increase the economic viability of small wind-power generation. In addition, it has the potential to eliminate lethality to birds and bats, overcome public objections to the aesthetics of wind-power machines, and significantly expand wind-power’s contribution to the national energy supply

Generating high quality libraries for DIA MS with empirically corrected peptide predictions.

Data-independent acquisition approaches typically rely on experiment-specific spectrum libraries, requiring offline fractionation and tens to hundreds of injections. We demonstrate a library generation workflow that leverages fragmentation and retention time prediction to build libraries containing every peptide in a proteome, and then refines those libraries with empirical data. Our method specifically enables rapid, experiment-specific library generation for non-model organisms, which we demonstrate using the malaria parasite Plasmodium falciparum, and non-canonical databases, which we show by detecting missense variants in HeLa

E. coli K-12 and EHEC Genes Regulated by SdiA

Background: Escherichia and Salmonella encode SdiA, a transcription factor of the LuxR family that regulates genes in response to N-acyl homoserine lactones (AHLs) produced by other species of bacteria. E. coli genes that change expression in the presence of plasmid-encoded sdiA have been identified by several labs. However, many of these genes were identified by overexpressing sdiA on a plasmid and have not been tested for a response to sdiA produced from its natural position in the chromosome or for a response to AHL. Methodology/Principal Findings: We determined that two important loci reported to respond to plasmid-based sdiA, ftsQAZ and acrAB, do not respond to sdiA expressed from its natural position in the chromosome or to AHLs. To identify genes that are regulated by chromosomal sdiA and/or AHLs, we screened 10,000 random transposon-based luciferase fusions in E. coli K-12 and a further 10,000 in E. coli O157:H7 for a response to AHL and then tested these genes for sdiAdependence. We found that genes encoding the glutamate-dependent acid resistance system are up-regulated, and fliE is down-regulated, by sdiA. Gene regulation by sdiA of E. coli is only partially dependent upon AHL. Conclusions/Significance: The genes of E. coli that respond to plasmid-based expression of sdiA are largely different than those that respond to chromosomal sdiA and/or AHL. This has significant implications for determining the true function o

Resolving the Gap and AU-scale Asymmetries in the Pre-transitional Disk of V1247 Orionis

archiveprefix: arXiv primaryclass: astro-ph.SR keywords: accretion, accretion disks, protoplanetary disks, stars: pre-main sequence, techniques: interferometric eid: 80 adsurl: http://adsabs.harvard.edu/abs/2013ApJ...768...80K adsnote: Provided by the SAO/NASA Astrophysics Data SystemarticlePre-transitional disks are protoplanetary disks with a gapped disk structure, potentially indicating the presence of young planets in these systems. In order to explore the structure of these objects and their gap-opening mechanism, we observed the pre-transitional disk V1247 Orionis using the Very Large Telescope Interferometer, the Keck Interferometer, Keck-II, Gemini South, and IRTF. This allows us to spatially resolve the AU-scale disk structure from near- to mid-infrared wavelengths (1.5-13 μm), tracing material at different temperatures and over a wide range of stellocentric radii. Our observations reveal a narrow, optically thick inner-disk component (located at 0.18 AU from the star) that is separated from the optically thick outer disk (radii gsim 46 AU), providing unambiguous evidence for the existence of a gap in this pre-transitional disk. Surprisingly, we find that the gap region is filled with significant amounts of optically thin material with a carbon-dominated dust mineralogy. The presence of this optically thin gap material cannot be deduced solely from the spectral energy distribution, yet it is the dominant contributor at mid-infrared wavelengths. Furthermore, using Keck/NIRC2 aperture masking observations in the H, K', and L' bands, we detect asymmetries in the brightness distribution on scales of ~15-40 AU, i.e., within the gap region. The detected asymmetries are highly significant, yet their amplitude and direction changes with wavelength, which is not consistent with a companion interpretation but indicates an inhomogeneous distribution of the gap material. We interpret this as strong evidence for the presence of complex density structures, possibly reflecting the dynamical interaction of the disk material with sub-stellar mass bodies that are responsible for the gap clearing.This work was done in part under contract with the California Institute of Technology (Caltech), funded by NASA through the Sagan Fellowship Program (S.K. and C.E. are Sagan Fellows). Data presented herein were obtained at the W. M. Keck Observatory from telescope time allocated to the National Aeronautics and Space Administration through the agency's scientific partnership with the California Institute of Technology and the University of California. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation. The authors wish to recognize and acknowledge the very significant cultural role and reverence that the summit of Mauna Kea has always had within the indigenous Hawaiian community. We are most fortunate to have the opportunity to conduct observations from this mountain. This work was supported in part by the Aerospace Corporation's Independent Research and Development (IR&D) program. This work was supported by NASA ADP grant NNX09AC73G

Oxandrolone in trauma patients

Study Objective To determine the effect of oxandrolone administration on nutritional and clinical outcomes after multiple trauma. Design Prospective, randomized, double-blind, placebo-controlled study. Setting. Level 1 trauma center in a university teaching hospital. Patients Sixty-two patients requiring enteral nutrition, 60 of whom completed the study. Intervention Patients were randomized to receive either oxandrolone 10 mg or placebo twice/day for a maximum of 28 days. Measurements and Main Results Total urinary nitrogen, prealbumin, nitrogen balance, total body water, and body cell mass were measured on day 1 of enteral nutrition and then at day 7, day 10, and study exit. Patients were assessed daily for metabolic and infectious complications. The two groups were similar for demographics and dosage of enteral nutrition. Measurement of total urinary nitrogen at study entry showed both groups to be highly catabolic (oxandrolone 17.2 ± 4.9, placebo 19.1 ± 10.8 g/day, NS). On days 7 and 10, total urinary nitrogen increased in both groups; however, there was no significant difference between groups. Nitrogen balance was negative throughout the study in each group. Body cell mass decreased slightly in both groups over the study period. Prealbumin serum concentrations increased significantly in both groups at day 10 and study exit compared with study entry. The groups did not differ significantly for length of hospital stay (oxandrolone 30.8 ± 17.9, placebo 27.0 ± 25.7 days), length of intensive care unit stay (oxandrolone 17.1 ± 7.8, placebo 15.5 ± 9.7 days), and frequency of pneumonia or sepsis (oxandrolone 48, placebo 43 episodes). Conclusion Oxandrolone 20 mg/day does not have obvious benefit in nutritional and clinical outcomes during the first month after multiple trauma

Resolving the gap and AU-scale asymmetries in pre-transitional disks of V1247 ORIONIS

adsurl: http://adsabs.harvard.edu/abs/2013prpl.conf2B051K adsnote: Provided by the SAO/NASA Astrophysics Data SystemPre-transitional disks are protoplanetary disks with a gapped disk structure, potentially indicating the presence of young planets in these systems. In order to explore the structure of these objects and their gap-opening mechanism, we observed the pre-transitional disk V1247 Orionis using the Very Large Telescope Interferometer, the Keck Interferometer, Keck-II, Gemini South, and IRTF. This allows us to spatially resolve the AU-scale disk structure from near- to mid-infrared wavelengths (1.5–13µm), tracing material at different temperatures and over a wide range of stellocentric radii. Our observations reveal a narrow, optically thick inner-disk component (located at 0.18 AU from the star) that is separated from the optically thick outer disk (radii !46 AU), providing unambiguous evidence for the existence of a gap in this pre-transitional disk. Surprisingly, we find that the gap region is filled with significant amounts of optically thin material with a carbon-dominated dust mineralogy. The presence of this optically thin gap material cannot be deduced solely from the spectral energy distribution, yet it is the dominant contributor at mid-infrared wavelengths. Furthermore, using Keck/NIRC2 aperture masking observations in the H, K′ , and L′ bands, we detect asymmetries in the brightness distribution on scales of ∼15–40 AU, i.e., within the gap region. The detected asymmetries are highly significant, yet their amplitude and direction changes with wavelength, which is not consistent with a companion interpretation but indicates an inhomogeneous distribution of the gap material. We interpret this as strong evidence for the presence of complex density structures, possibly reflecting the dynamical interaction of the disk material with sub-stellar mass bodies that are responsible for the gap clearing.NASA through the Sagan Fellowship ProgramW. M. Keck FoundationAerospace Corporation’s Independent Research and Development (IR&D) programNASA AD

Lorecivivint, a Novel Intraarticular CDC‐like Kinase 2 and Dual‐Specificity Tyrosine Phosphorylation‐Regulated Kinase 1A Inhibitor and Wnt Pathway Modulator for the Treatment of Knee Osteoarthritis: A Phase II Randomized Trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162805/2/art41315_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162805/1/art41315.pd

Combined kinase inhibitors of MEK1/2 and either PI3K or PDGFR are efficacious in intracranial triple-negative breast cancer

Background: Triple-negative breast cancer (TNBC), lacking expression of hormone and human epidermal growth factor receptor 2 receptors, is an aggressive subtype that frequently metastasizes to the brain and has no FDA-approved systemic therapies. Previous literature demonstrates mitogen-Activated protein kinase kinase (MEK) pathway activation in TNBC brain metastases. Thus, we aimed to discover rational combinatorial therapies with MEK inhibition, hypothesizing that co-inhibition using clinically available brain-penetrant inhibitors would improve survival in preclinical models of TNBC brain metastases. Methods: Using human-derived TNBC cell lines, synthetic lethal small interfering RNA kinase screens were evaluated with brain-penetrant inhibitors against MEK1/2 (selumetinib, AZD6244) or phosphatidylinositol-3 kinase (PI3K; buparlisib, BKM120). Mice bearing intracranial TNBC tumors (SUM149, MDA-MB-231Br, MDA-MB-468, or MDA-MB-436) were treated with MEK, PI3K, or platelet derived growth factor receptor (PDGFR; pazopanib) inhibitors alone or in combination. Tumors were analyzed by western blot and multiplexed kinase inhibitor beads/mass spectrometry to assess treatment effects. Results: Screens identified MEK+PI3K and MEK+PDGFR inhibitors as tractable, rational combinations. Dual treatment of selumetinib with buparlisib or pazopanib was synergistic in TNBC cells in vitro. Both combinations improved survival in intracranial SUM149 and MDA-MB-231Br, but not MDA-MB-468 or MDA-MB-436. Treatments decreased mitogen-Activated protein kinase (MAPK) and PI3K (Akt) signaling in sensitive (SUM149 and 231Br) but not resistant models (MDA-MB-468). Exploratory analysis of kinome reprogramming in SUM149 intracranial tumors after MEK PI3K inhibition demonstrates extensive kinome changes with treatment, especially in MAPK pathway members. Conclusions: Results demonstrate that rational combinations of the clinically available inhibitors selumetinib with buparlisib or pazopanib may prove to be promising therapeutic strategies for the treatment of some TNBC brain metastases. Additionally, effective combination treatments cause widespread alterations in kinase pathways, including targetable potential resistance drivers

Extreme Asymmetry in the Disk of V1247 Ori

We present the first near-infrared scattered-light detection of the transitional disk around V1247 Ori, which was obtained using high-resolution polarimetric differential imaging observations with Subaru/HiCIAO. Our imaging in the H band reveals the disk morphology at separations of ~0.14"-0.86" (54-330 au) from the central star. The polarized intensity (PI) image shows a remarkable arc-like structure toward the southeast of the star, whereas the fainter northwest region does not exhibit any notable features. The shape of the arm is consistent with an arc of 0.28" $\pm$ 0.09" in radius (108 au from the star), although the possibility of a spiral arm with a small pitch angle cannot be excluded. V1247 Ori features an exceptionally large azimuthal contrast in scattered, polarized light; the radial peak of the southeastern arc is about three times brighter than the northwestern disk measured at the same distance from the star. Combined with the previous indication of an inhomogeneous density distribution in the gap at $\lesssim$46 au, the notable asymmetry in the outer disk suggests the presence of unseen companions and/or planet-forming processes ongoing in the arc.Comment: 21 pages, 5 figures, accepted for publication in PAS