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Response of a Memristive Biomembrane and Demonstration of Potential Use in Online Learning

The pervasive von Neumann architecture uses complex processor cores and sequential computation. In contrast, the brain is massively parallel and highly efficient, owing to the ability of the neurons and synapses to store and process information simultaneously and to adapt according to incoming information. These features have motivated researchers to develop a host of brain-inspired computers, devices, and models, collectively referred to as neuromorphic computing systems. The quest for synaptic materials capable of closely mimicking biological synapses has led to an alamethicin-doped, synthetic biomembrane with volatile memristive properties which can emulate key synaptic functions to facilitate learning and computation. In contrast to its solid-state counterparts, this two-terminal, biomolecular memristor features similar structure, switching mechanisms, and ionic transport modality as biological synapses while consuming considerably lower power. To use the device as a circuit element, it is important to understand its response to different kinds of input signals. Here we develop a simplified closed form analytical solution based on the underlying state equations for pulse and sine wave inputs. A Verilog-A model based on Runge-Kutta method was developed to incorporate the device in a circuit simulator. Finally, the paper demonstrates possible applications for short- and long-term learning using its unique volatile memristive properties.

Hasan, Md Sakib↗

Chapter 15: Reliability of Wind Turbines

The global wind industry has witnessed exciting developments in recent years. The future will be even brighter with further reductions in capital and operation and maintenance costs, which can be accomplished with improved turbine reliability, especially when turbines are installed offshore. One opportunity for the industry to improve wind turbine reliability is through the exploration of reliability engineering life data analysis based on readily available data or maintenance records collected at typical wind plants. If adopted and conducted appropriately, these analyses can quickly save operation and maintenance costs in a potentially impactful manner. This chapter discusses wind turbine reliability by highlighting the methodology of reliability engineering life data analysis. It first briefly discusses fundamentals for wind turbine reliability and the current industry status. Then, the reliability engineering method for life analysis, including data collection, model development, and forecasting, is presented in detail and illustrated through two case studies. The chapter concludes with some remarks on potential opportunities to improve wind turbine reliability. An owner and operator's perspective is taken and mechanical components are used to exemplify the potential benefits of reliability engineering analysis to improve wind turbine reliability and availability.

17 WIND ENERGY↗

Chapter 14 - Reliability of Wind Turbines

The global wind energy industry has grown at a fast pace during the past half-decade. Advancements from design and manufacturing to operation and maintenance have led to reduced capital and maintenance costs, which make wind power an indispensable source for a comprehensive solution to global electricity needs. Once wind turbines are installed, the opportunity to lower wind power costs is mainly through improved operation and maintenance practices. Modern wind turbines are equipped with tens or hundreds of measurement channels and are generating an abundance of data, with lot of efforts being put into data analysis by both the research community and the industry. One type of analysis is through the exploration of reliability engineering methods based on readily available data or maintenance records collected at typical wind power plants. If adopted and conducted appropriately, these analyses can quickly save operation and maintenance costs in a potentially impactful manner. The wind industry has adopted this discipline more broadly in recent years. This chapter discusses wind turbine reliability by highlighting the methodology of reliability engineering life data analysis. It first briefly discusses the fundamentals of wind turbine reliability and the current industry status. Then, the reliability engineering method for life analysis, including data collection, model development, and forecasting, is presented in detail and illustrated through two case studies. The chapter concludes with some remarks on potential opportunities to improve wind turbine reliability. An owner and operator's perspective is taken and mechanical components are used to exemplify the potential benefits of reliability engineering analysis to improve wind turbine reliability and availability.

database↗

$\gamma$-Unstable Bohr Hamiltonian with sextic potential for odd-A nuclei

We report in this paper, odd-A nuclei in the vibrational to γ-soft transitional region are studied in the collective model, in which the odd-A system is described by the Bohr Hamiltonian with the quasi exactly solvable sextic β-part potential for the even-even core coupled with a single nucleon in a j = 3/2 orbit via the β-independent five-dimensional spin-orbit interaction and the total angular momentum degeneracy breaking term. To test the validity of the coupling scheme, we use the model to reproduce experimentally available level energies and B(E2) values of 187,189,191,193,195 Ir. It is clearly shown from both the level energies and the known B(E2) values for 191,193I r fitted that the model with the β-independent five-dimensional spin-orbit interaction and the total angular momentum degeneracy breaking term seems adequate to describe the low-lying level pattern and the structure of these odd-A nuclei.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Inhibition of glycolysis by a novel EGFR/HER2 inhibitor KU004 suppresses the growth of HER2+ cancer

Upregulation of glycolysis was often observed in human HER2-overexpressing cancers. In this study, we demonstrated that KU004, a dual novel EGFR/HER2 inhibitor, disrupted cancer cell proliferation via modulation of glycolysis. KU004, inhibited the Warburg effect by suppressing hexokinase II (HK2) expression at the transcriptional and post-translational levels. Further study demonstrated that the downregulation of HKII by KU004 was mainly mediated by the PI3K/Akt signaling pathway. Furthermore, the role of HKII downregulation in KU004-mediated antitumor effect was also confirmed in our in vivo xenograft model. Collectively, these data suggest that multifaceted targeting the aberrant glucose metabolism along with the upstream HER2 may be an effective approach for clinical treatment against HER2+ cancer. - Highlights: • KU004suppressed the glucose metabolism in HER2-overexpressing cancer cells. • KU004 inhibited HKII expression both transcriptionally and post-translationally. • The downregulation of HKII is mediated by the PI3K/Akt signaling pathway. • KU004 inhibited HKII expression and the growth of HER2-overexpressing cells both in vitro and in vivo.

60 APPLIED LIFE SCIENCES↗

Combinatorial gene inactivation of aldehyde dehydrogenases mitigates aldehyde oxidation catalyzed by E. coli resting cells

Aldehydes are attractive chemical targets both as end products in the flavors and fragrances industry and as synthetic intermediates due to their propensity for C–C bond formation. Here, in this study, we identify and address unexpected oxidation of a model collection of aromatic aldehydes, including many that originate from biomass degradation. When diverse aldehydes are supplemented to E. coli cells grown under aerobic conditions, as expected they are either reduced by the wild-type MG1655 strain or stabilized by a strain engineered for reduced aromatic aldehyde reduction (the E. coli RARE strain). Surprisingly, when these same aldehydes are supplemented to resting cell preparations of either E. coli strain, under many conditions we observe substantial oxidation. By performing combinatorial inactivation of six candidate aldehyde dehydrogenase genes in the E. coli genome using multiplexed automatable genome engineering (MAGE), we demonstrate that this oxidation can be substantially slowed, with greater than 50% retention of 6 out of 8 aldehydes when assayed 4 h after their addition. Given that our newly engineered strain exhibits reduced oxidation and reduction of aromatic aldehydes, we dubbed it the E. coli ROAR strain. We applied the new strain to resting cell biocatalysis for two kinds of reactions – the reduction of 2-furoic acid to furfural and the condensation of 3-hydroxybenzaldehyde and glycine to form a non-standard β-hydroxy-α-amino acid. In each case, we observed substantial improvements in product titer 20 h after reaction initiation (9-fold and 10-fold, respectively). Moving forward, the use of this strain to generate resting cells should allow aldehyde product isolation, further enzymatic conversion, or chemical reactivity under cellular contexts that better accommodate aldehyde toxicity.

59 BASIC BIOLOGICAL SCIENCES↗

Phage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model

Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus. We also characterize immune responses elicited following administration of the phage cocktail. While minimal innate responses are observed after phage administration, two rounds of treatment induces phage-specific neutralizing antibodies and accelerate phage clearance from tissues. Interestingly, the myophages in our cocktail induce a more robust neutralizing antibody response than the siphophages. This anti-phage immunity reduces the effectiveness of the phage cocktail in our murine model. Collectively, this study shows phage-specific immune responses may be an important consideration in the development of phage cocktails for therapeutic use.

60 APPLIED LIFE SCIENCES↗

Sestrin2 inhibits mTORC1 through modulation of GATOR complexes

Sestrins are stress-inducible metabolic regulators that suppress a wide range of age- and obesity-associated pathologies, many of which are due to mTORC1 overactivation. Upon various stresses, the Sestrins inhibit mTORC1 activity through an indirect mechanism that is still unclear. GATORs are recently identified protein complexes that regulate the activity of RagB, a small GTPase essential for mTORC1 activation. GATOR1 is a GTPase activating protein (GAP) for RagB whereas GATOR2 functions as an inhibitor of GATOR1. However, how the GATORs are physiologically regulated is unknown. Here we show that Sestrin2 binds to GATOR2, and liberates GATOR1 from GATOR2-mediated inhibition. Released GATOR1 subsequently binds to and inactivates RagB, ultimately resulting in mTORC1 suppression. Consistent with this biochemical mechanism, genetic ablation of GATOR1 nullifies the mTORC1-inhibiting effect of Sestrin2 in both cell culture and Drosophila models. Collectively, we elucidate a new signaling cascade composed of Sestrin2-GATOR2-GATOR1-RagB that mediates stress-dependent suppression of mTORC1 activity.

59 BASIC BIOLOGICAL SCIENCES↗

Directional clogging and phase separation for disk flow through periodic and diluted obstacle arrays

We model collective disk flow though a square array of obstacles as the flow direction is changed relative to the symmetry directions of the array. At lower disk densities there is no clogging for any driving direction, but as the disk density increases, the average disk velocity decreases and develops a drive angle dependence. For certain driving angles, the flow is reduced or drops to zero when the system forms a heterogeneous clogged state consisting of high density clogged regions coexisting with empty regions. The clogged states are fragile and can be unclogged by changing the driving angle. For large obstacle sizes, we find a uniform clogged state that is distinct from the collective clogging regime. Within the clogged phases, depinning transitions can occur as a function of increasing driving force, with intermittent motion appearing just above the depinning threshold. The clogging is robust against the random removal or dilution of the obstacle sites, and the disks are able to form system-spanning clogged clusters even under increasing dilution. If the dilution becomes too large, however, the clogging behavior is lost.

36 MATERIALS SCIENCE↗

SPIRAL ARMS IN THE ASYMMETRICALLY ILLUMINATED DISK OF MWC 758 AND CONSTRAINTS ON GIANT PLANETS

We present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets and Disks with Subaru, and 1.1 {mu}m Hubble Space Telescope/NICMOS data. While submillimeter studies suggested there is a dust-depleted cavity with r = 0.''35, we find scattered light as close as 0.''1 (20-28 AU) from the star, with no visible cavity at H, K', or K{sub s} . We find two small-scaled spiral structures that asymmetrically shadow the outer disk. We model one of the spirals using spiral density wave theory, and derive a disk aspect ratio of h {approx} 0.18, indicating a dynamically warm disk. If the spiral pattern is excited by a perturber, we estimate its mass to be 5{sup +3} {sub -4} M{sub J} , in the range where planet filtration models predict accretion continuing onto the star. Using a combination of non-redundant aperture masking data at L' and angular differential imaging with Locally Optimized Combination of Images at K' and K{sub s} , we exclude stellar or massive brown dwarf companions within 300 mas of the Herbig Ae star, and all but planetary mass companions exterior to 0.''5. We reach 5{sigma} contrasts limiting companions to planetary masses, 3-4 M{sub J} at 1.''0 and 2 M{sub J} at 1.''55, using the COND models. Collectively, these data strengthen the case for MWC 758 already being a young planetary system.

79 ASTRONOMY AND ASTROPHYSICS↗

Expectations for the hard x-ray continuum and gamma-ray line fluxes from the typE IA supernova SN 2014J in M82

The hard X-ray continuum and gamma-ray lines from a Type Ia supernova dominate its integrated photon emissions and can provide unique diagnostics of the mass of the ejecta, the {sup 56}Ni yield and spatial distribution, its kinetic energy and expansion speed, and the mechanism of explosion. Such signatures and their time behavior 'X-ray' the bulk debris field in direct fashion, and do not depend on the ofttimes problematic and elaborate UV, optical, and near-infrared spectroscopy and radiative transfer that have informed the study of these events for decades. However, to date no hard photons have ever been detected from a Type Ia supernova in explosion. With the advent of the supernova SN 2014J in M82, at a distance of ∼3.5 Mpc, this situation may soon change. Both NuSTAR and INTEGRAL have the potential to detect SN 2014J, and, if spectra and light curves can be measured, would usefully constrain the various explosion models published during the last ∼30 yr. In support of these observational campaigns, we provide predictions for the hard X-ray continuum and gamma-line emissions for 15 Type Ia explosion models gleaned from the literature. The model set, containing as it does deflagration, delayed detonation, merger detonation, pulsational delayed detonation, and sub-Chandrasekhar helium detonation models, collectively spans a wide range of properties, and hence signatures. We provide a brief discussion of various diagnostics (with examples), but importantly make the spectral and line results available electronically to aid in the interpretation of the anticipated data.

79 ASTRONOMY AND ASTROPHYSICS↗

Investigation of the isoscalar response of 24 Mg to 6 Li scattering

24 Mg is a strongly deformed nucleus in the ground state. Deformation effects can be observed in the structure of the isoscalar giant monopole and quadrupole resonances. 24 Mg is also a nucleus that is well known to present different types of cluster-oscillation modes. Both giant resonances and cluster states are strongly populated by isoscalar transitions. To extract the E0, E1, and E2 transition strengths via 6 Li scattering. The 6 Li probe is a powerful tool for investigating the isoscalar nuclear response with a very favorable ratio of resonance-to-continuum background. Double-differential cross sections of 6 Li inelastic scattering, at the beam energy of 100 MeV/u, were measured in the excitation-energy range 10 – 40 MeV and scattering angles 0 - 3°. A multipole-decomposition analysis was performed for extracting the isoscalar E0 , E1, and E2 strength distributions. Results: The extracted multipole strengths were compared with predictions from consistent quasiparticle random phase approximation calculations. The theoretical predictions are in fair agreement with the experimental data. The E0 strength was also compared with results from antisymmetrized molecular dynamics calculations found in the literature. A few peaks in the experimental data might be associated with clustering in 24 Mg. Ground-state deformation effects were observed in the isoscalar giant monopole resonance (ISGMR) and isoscalar giant quadrupole resonance (ISGQR) distributions. The ISGMR strength is split in two peaks around 19 and 28 MeV. The ISGQR exhibits a pronounced peak at 20 MeV with a broadening at the low-energy region, similar to predictions from microscopic calculations. Signatures of excitation of cluster states were observed in the E0 response. Further studies including particle-decay measurements will be required to confirm the nature of the observed peaks.

20 ≤ A ≤ 38↗

Two-way coupled particle-turbulence interaction: Effect of numerics and resolution on fluid and particle statistics

Euler-Lagrange point-particle simulation has emerged as a premier methodology for studying dispersed particle-laden flows. This method's popularity stems from its ability to resolve fine-scale fluid structures while also tracking individual particles at reduced cost using an appropriate particle acceleration model. However, the point-particle model has known convergence issues in that refinement of the fluid grid can lead to changes in the predicted statistics. The reasons for non-convergence are twofold: the point-particle two-way coupling force in the Navier-Stokes equations requires a numerical regularization and, without careful implementation, yields a singular force on the fluid with grid refinement. The second factor that yields grid-dependent statistics is that the point-particle force model in general depends on the undisturbed fluid velocity. When the undisturbed fluid velocity is not robustly modeled in a grid-insensitive way, the calculated force for both particles and fluid will be grid-dependent, contaminating their respective statistics. While the first issue regarding regularizing the point-particle source term has received attention in the literature, the consequences of robustly modeling the undisturbed velocity in the context of grid refinement of turbulence has received little attention. Here, we consider decaying homogeneous isotropic turbulence laden with particles at different Stokes numbers. For a given Stokes number, we systematically refine the grid and demonstrate that explicitly modeling the undisturbed fluid velocity yields relative grid insensitivity for the energy of the particle and fluid phases, as well as acceleration of the particles. We also demonstrate that an appropriately defined dissipation rate is also grid-insensitive when an undisturbed fluid velocity correction is used. In contrast, when the undisturbed fluid velocity is modeled using the conventional approach of interpolating the local fluid velocity to the particle location, we show this procedure yields divergent statistics with grid refinement. In particular, we show that higher-order interpolation of the fluid velocity in two-way coupled problems is worse than lower-order interpolation, in the absence of a correction procedure to estimate the undisturbed fluid velocity. We also examine velocity derivative statistics of the fluid phase and demonstrate that these statistics are not in general convergent even when the undisturbed fluid velocity is explicitly modeled. Collectively, the observations in this paper are used to present a philosophy on the types of questions which are answerable with point-particle methods.

42 ENGINEERING↗

Fingerprinting Anomalous Computation with RNN for GPU-accelerated HPC Machines

This paper presents a workload classification framework that discriminates illicit computation from authorized workloads on GPU-accelerated HPC systems. As such systems become more and more powerful, they are exploited by attackers to run malicious and for-profit programs that typically require extremely high computing ability to be successful. Our classification framework leverages the distinctive signatures between illicit and authorized workloads, and explore machine learning methods to learn the workloads and classify them. The framework uses lightweight, non-intrusive workload profiling to collect model input data, and explores multiple machine learning methods, particularly recurrent neural network (RNN) that is suitable for online anomalous workload detection. Evaluation results on four generations of GPU machines demonstrate that the workload classification framework can tell apart the illicit authorized workloads with a high accuracy of over 95%.

Zou, Pengfei↗

SU-E-T-73: Commissioning of a Treatment Planning System for Proton Spot Scanning

Purpose: A treatment planning system (TPS) was commissioned for clinical use with a fixed beam line proton delivery system. An outline of the data collection, modeling, and verification is provided. Methods: Beam data modeling for proton spot scanning in CMS Xio TPS requires the following measurements: (i) integral depth dose curves (IDDCs); (ii) absolute dose calibration; and (iii) beam spot characteristics. The IDDCs for 18 proton energies were measured using an integrating detector in a single spot field in a water phantom. Absolute scaling of the IDDCs were performed based on ion chamber measurements in mono-energetic 10×10 cm{sup 2} fields in water. Beam spot shapes were measured in air using a flat panel scintillator detector at multiple planes. For beam model verification, more than 45 uniform dose phantom and patient plans were generated. These plans were used to measure range, point dose, and longitudinal and lateral profiles. Tolerances employed for verification are: point dose and longitudinal profiles, ±2%; range, ±1 mm; FWHM for lateral profiles, ±2 mm; and patient plan dose distribution, gamma index of >90% at 3%/3 mm criteria. Results: More than 97% of the point dose measurements out of 115 were within +/-2% with maximum deviation of 3%. 98% of the ranges measured were within 1 mm with maximum deviation of 1.4mm. The normalized depth doses were within 2% at all depths. The maximum error in FWHM of lateral profiles was found to be less than 2mm. For 5 patient plans representing different anatomic sites, a total of 38 planes for 12 beams were analyzed for gamma index with average value of 99% and minimum of 94%. Conclusions: The planning system is successfully commissioned and can be safely deployed for clinical use. Measurements of IDDCs on user beam are highly recommended instead of using standard beam IDDCs.

60 APPLIED LIFE SCIENCES↗

SU-E-T-188: Commission of World 1st Commercial Compact PBS Proton System

Purpose: ProteusONE is the 1st commercial compact PBS proton system with an upstream scanning gantry and C230 cyclotron. We commissioned XiO and Raystation TPS simultaneously. This is a summary of beam data collection, modeling, and verification and comparison without range shiter for this unique system with both TPS. Methods: Both Raystation and XiO requires the same measurements data: (i) integral depth dose(IDDs) of single central spot measured in water tank; (ii) absolute dose calibration measured at 2cm depth of water with mono-energetic 10×10 cm2 field with spot spacing 4mm, 1MU per spot; and (iii) beam spot characteristics in air at 0cm and ± 20cm away from ISO. To verify the beam model for both TPS, same 15 cube plans were created to simulate different treatment sites, target volumes and positions. PDDs of each plan were measured using a Multi-layer Ionization Chamber(MLIC), absolute point dose verification were measured using PPC05 in water tank and patient-specific QA were measured using MatriXX PT, a 2D ion chamber array. Results: All the point dose measurements at midSOBP were within 2% for both XiO and Raystation. However, up to 5% deviations were observed in XiO’s plans at shallow depth while within 2% in Raystation plans. 100% of the ranges measured were within 1 mm with maximum deviation of 0.5 mm. 20 patient specific plan were generated and measured in 3 planes (distal, proximal and midSOBP) in Raystation. The average of gamma index is 98.7%±3% with minimum 94% Conclusions: Both TPS were successfully commissioned and can be safely deployed for clinical use for ProteusONE. Based on our clinical experience in PBS planning, user interface, function and workflow, we preferably use Raystation as our main clinical TPS. Gamma Index >95% at 3%/3 mm criteria is our institution action level for patient specific plan QAs.

60 APPLIED LIFE SCIENCES↗

Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age

Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen interactions and infectious disease mechanisms, these reductionist models lack many essential features present in the native host microenvironment that are known to regulate infection, including three-dimensional (3-D) architecture, multicellular complexity, commensal microbiota, gas exchange and nutrient gradients, and physiologically relevant biomechanical forces (e.g., fluid shear, stretch, compression). Here, a major challenge in tissue engineering for infectious disease research is recreating this dynamic 3-D microenvironment (biological, chemical, and physical/mechanical) to more accurately model the initiation and progression of host-pathogen interactions in the laboratory. Here we review selected 3-D models of human intestinal mucosa, which represent a major portal of entry for infectious pathogens and an important niche for commensal microbiota. We highlight seminal studies that have used these models to interrogate host-pathogen interactions and infectious disease mechanisms, and we present this literature in the appropriate historical context. Models discussed include 3-D organotypic cultures engineered in the rotating wall vessel (RWV) bioreactor, extracellular matrix (ECM)-embedded/organoid models, and organ-on-a-chip (OAC) models. Collectively, these technologies provide a more physiologically relevant and predictive framework for investigating infectious disease mechanisms and antimicrobial therapies at the intersection of the host, microbe, and their local microenvironments.

3-D↗

Photovoltaics Informatics: Harnessing Energy Science via Data-Driven Approaches

We discuss our current research focus on photovoltaic (PV) informatics, which is dedicated to functionality enhancement of solar materials through data management and data mining-aided, integrated computational materials engineering (ICME) for rapid screening and identification of multi-scale processing/structure/property/performance relationships. Our current PV informatics research ranges from transparent conducting oxides (TCO) to solar absorber materials. As a test bed, we report on examples of our current data management system for PV research and advanced data mining to improve the performance of solar cells such as CuInxGa1-xSe2 (CIGS) aiming at low-cost and high-rate processes. For the PV data management, we show recent developments of a strategy for data modeling, collection and aggregation methods, and construction of data interfaces, which enable proper archiving and data handling for data mining. For scientific data mining, the value of high-dimensional visualizations and non-linear dimensionality reduction is demonstrated to quantitatively assess how process conditions or properties are interconnected in the context of the development of Al-doped ZnO (AZO) thin films as the TCO layers for CIGS devices. Such relationships between processing and property of TCOs lead to optimal process design toward enhanced performance of CIGS cells/devices.

CONSTRUCTION↗