C.S. Lewis\u27s Ontological View of the Demonic: Satan as an Explanatory Postulate

In his Space Trilogy, C.S. Lewis speaks on the nature of demons and angels, revealing their interactions and influence on mankind, as well as their role in God’s plan

Highly multiplexed label-free imaging sensor for accurate quantification of small-molecule binding kinetics

Investigating the binding interaction of small molecules to large ligands is a compelling task for the field of drug development, as well as agro-biotechnology, since a common trait of drugs and toxins is often a low molecular weight (MW). Here, we improve the limit of detection of the Interferometric Reflectance Imaging Sensor (IRIS), a label-free, highly multiplexed biosensor, to perform small-molecule screening. In this work, characterization of small molecules binding to immobilized probes in a microarray format is demonstrated, with a limit of detection of 1 pg/mm2 in mass density. First, as a proof of concept to show the impact of spatial and temporal averaging on the system noise, detection of biotin (MW = 244.3 Da) binding to a streptavidin-functionalized chip is performed and the parameters are tuned to achieve maximum signal-to-noise ratio (SNR ≈ 34). The optimized system is then applied to the screening of a 20-multiplexed antibody chip against fumonisin B1 (MW = 721.8 Da), a mycotoxin found in cereal grains. The simultaneously recorded binding curves yield an SNR ≈ 8. Five out of twenty antibodies are also screened against the toxin in a lateral flow assay, obtaining consistent results. With the demonstrated noise characteristics, further sensitivity improvements are expected with the advancement of camera sensor technology.Published versio

Final report on LDRD project : single-photon-sensitive imaging detector arrays at 1600 nm.

The key need that this project has addressed is a short-wave infrared light detector for ranging (LIDAR) imaging at temperatures greater than 100K, as desired by nonproliferation and work for other customers. Several novel device structures to improve avalanche photodiodes (APDs) were fabricated to achieve the desired APD performance. A primary challenge to achieving high sensitivity APDs at 1550 nm is that the small band-gap materials (e.g., InGaAs or Ge) necessary to detect low-energy photons exhibit higher dark counts and higher multiplication noise compared to materials like silicon. To overcome these historical problems APDs were designed and fabricated using separate absorption and multiplication (SAM) regions. The absorption regions used (InGaAs or Ge) to leverage these materials 1550 nm sensitivity. Geiger mode detection was chosen to circumvent gain noise issues in the III-V and Ge multiplication regions, while a novel Ge/Si device was built to examine the utility of transferring photoelectrons in a silicon multiplication region. Silicon is known to have very good analog and GM multiplication properties. The proposed devices represented a high-risk for high-reward approach. Therefore one primary goal of this work was to experimentally resolve uncertainty about the novel APD structures. This work specifically examined three different designs. An InGaAs/InAlAs Geiger mode (GM) structure was proposed for the superior multiplication properties of the InAlAs. The hypothesis to be tested in this structure was whether InAlAs really presented an advantage in GM. A Ge/Si SAM was proposed representing the best possible multiplication material (i.e., silicon), however, significant uncertainty existed about both the Ge material quality and the ability to transfer photoelectrons across the Ge/Si interface. Finally a third pure germanium GM structure was proposed because bulk germanium has been reported to have better dark count properties. However, significant uncertainty existed about the quantum efficiency at 1550 nm the necessary operating temperature. This project has resulted in several conclusions after fabrication and measurement of the proposed structures. We have successfully demonstrated the Ge/Si proof-of-concept in producing high analog gain in a silicon region while absorbing in a Ge region. This has included significant Ge processing infrastructure development at Sandia. However, sensitivity is limited at low temperatures due to high dark currents that we ascribe to tunneling. This leaves remaining uncertainty about whether this structure can achieve the desired performance with further development. GM detection in InGaAs/InAlAs, Ge/Si, Si and pure Ge devices fabricated at Sandia was shown to overcome gain noise challenges, which represents critical learning that will enable Sandia to respond to future single photon detection needs. However, challenges to the operation of these devices in GM remain. The InAlAs multiplication region was not found to be significantly superior to current InP regions for GM, however, improved multiplication region design of InGaAs/InP APDs has been highlighted. For Ge GM detectors it still remains unclear whether an optimal trade-off of parameters can achieve the necessary sensitivity at 1550 nm. To further examine these remaining questions, as well as other application spaces for these technologies, funding for an Intelligence Community post-doc was awarded this year

Genome of the Asian Longhorned Beetle (\u3cem\u3eAnoplophora glabripennis\u3c/em\u3e), a Globally Significant Invasive Species, Reveals Key Functional and Evolutionary Innovations at the Beetle-Plant Interface

Background: Relatively little is known about the genomic basis and evolution of wood-feeding in beetles. We undertook genome sequencing and annotation, gene expression assays, studies of plant cell wall degrading enzymes, and other functional and comparative studies of the Asian longhorned beetle, Anoplophora glabripennis, a globally significant invasive species capable of inflicting severe feeding damage on many important tree species. Complementary studies of genes encoding enzymes involved in digestion of woody plant tissues or detoxification of plant allelochemicals were undertaken with the genomes of 14 additional insects, including the newly sequenced emerald ash borer and bull-headed dung beetle. Results: The Asian longhorned beetle genome encodes a uniquely diverse arsenal of enzymes that can degrade the main polysaccharide networks in plant cell walls, detoxify plant allelochemicals, and otherwise facilitate feeding on woody plants. It has the metabolic plasticity needed to feed on diverse plant species, contributing to its highly invasive nature. Large expansions of chemosensory genes involved in the reception of pheromones and plant kairomones are consistent with the complexity of chemical cues it uses to find host plants and mates. Conclusions: Amplification and functional divergence of genes associated with specialized feeding on plants, including genes originally obtained via horizontal gene transfer from fungi and bacteria, contributed to the addition, expansion, and enhancement of the metabolic repertoire of the Asian longhorned beetle, certain other phytophagous beetles, and to a lesser degree, other phytophagous insects. Our results thus begin to establish a genomic basis for the evolutionary success of beetles on plants

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Genome of the Asian longhorned beetle (Anoplophora glabripennis), a globally significant invasive species, reveals key functional and evolutionary innovations at the beetle–plant interface

Background Relatively little is known about the genomic basis and evolution of wood-feeding in beetles. We undertook genome sequencing and annotation, gene expression assays, studies of plant cell wall degrading enzymes, and other functional and comparative studies of the Asian longhorned beetle, Anoplophora glabripennis, a globally significant invasive species capable of inflicting severe feeding damage on many important tree species. Complementary studies of genes encoding enzymes involved in digestion of woody plant tissues or detoxification of plant allelochemicals were undertaken with the genomes of 14 additional insects, including the newly sequenced emerald ash borer and bull-headed dung beetle. Results The Asian longhorned beetle genome encodes a uniquely diverse arsenal of enzymes that can degrade the main polysaccharide networks in plant cell walls, detoxify plant allelochemicals, and otherwise facilitate feeding on woody plants. It has the metabolic plasticity needed to feed on diverse plant species, contributing to its highly invasive nature. Large expansions of chemosensory genes involved in the reception of pheromones and plant kairomones are consistent with the complexity of chemical cues it uses to find host plants and mates. Conclusions Amplification and functional divergence of genes associated with specialized feeding on plants, including genes originally obtained via horizontal gene transfer from fungi and bacteria, contributed to the addition, expansion, and enhancement of the metabolic repertoire of the Asian longhorned beetle, certain other phytophagous beetles, and to a lesser degree, other phytophagous insects. Our results thus begin to establish a genomic basis for the evolutionary success of beetles on plants

Session 8

Paradise Imperiled in Perelandra - Ted Dorman C.S. Lewis\u27s Ontological View of the Demonic: Satan as an Explanatory Postulate - John David Geib Virtue, Civilization and the Restitution of Man - Angus J.L. Menug