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Silicon and germanium suspended waveguides for the mid-infrared
No full textBoth silicon and germanium are very interesting materials for mid-infrared applications, particularly sensing, due to their low material losses at long wavelengths. Silicon is low loss up to 8 \u3bcm, and germanium up to 15 \u3bcm. To fully exploit these long wavelength transmission ranges of Si and Ge, and to build Si and Ge long wavelength photonic circuits, cladding materials need to have the same or larger transmission wavelength ranges than Si or Ge. One solution is to remove a lossy substrate and create Si and Ge suspended structures with air cladding. In the case of SOI, buried oxide can be removed by HF, and for the Ge-on-Si platform, Si substrate can be removed by TMAH. In this paper we report on the fabrication and characterization of suspended Ge waveguides at a wavelength of 3.8 \u3bcm, and on Si waveguides operating at a wavelength of 7.7 \u3bcm, both of which are the longest reported wavelengths for the two platformsPeer reviewed: YesNRC publication: Ye
In silico modelling and of monoclonal antibody fed-batch production in CHO cell
No full textBackground: Chinese hamster ovary (CHO) cells are highly important host cells in recombinant DNA technology. The rapid ability to conduct experiments in silico, using mathematical models of growing CHO cells, has helped advance the optimization of bioreactor conditions towards higher viable cell concentrations and mAb production. Several kinetic and system level models have been proposed for CHO cells. Results: In this work we have provided a new kinetic model of CHO cell metabolism and have shown its application for the simulation of novel high-throughput metabolomics data for fed-batch production in bioreactors with CHO cells grown using two feeding strategies. RNASeq data from CHO cells was used to guide selection of major metabolic pathways that were included in the kinetic model. The kinetic model includes 37 completely described reactions processing 45 species (metabolites). This model is based on previously published kinetic characteristics for this system and was evaluated against metabolomics data for CHO cells grown under two different feeding regimes. Conclusions: This work provides kinetic model for energy metabolism of CHO cells. Application of the model offers insights into possible causes of different performance of two feeding strategies, thus suggesting possible problems and future optimization routes.Peer reviewed: YesNRC publication: Ye
Re-evaluation of the gravity transfer component of the NRC Kibble balance
No full textWe describe a project to re-eval uate the transfer of the absolute determination of the local acceleration due to gravity from a nearby site, to the center of mass of the test mass in the NRC Kibble Ba lance. This re-evaluation includes the Characterization of the sensitivity of a relative gravity meter to the fringing magnetic flux density, as well as the attenuation provided by a simple magnetic shield.Peer reviewed: YesNRC publication: Ye
Theoretical and experimental study of ice accretion due to freezing rain on an inclined cylinder
No full textThis paper reports on an investigation of ice formation on a cylinder exposed to freezing rain. Freezing rain icing is characterized by supercooled raindrop impingement, with vertical and horizontal velocity components, water flow over the surface driven by aerodynamic and gravity forces, and freezing or shedding of the surface water. In the first part of the paper, a novel, three-dimensional analytical model of ice growth on a cylinder is derived and the results are discussed. This is followed by a discussion of experimental tests in the NRC Altitude Icing Wind Tunnel. The experiments were constrained to horizontal drop impingement, and we encountered difficulties delivering large drops at low speed to the test section. Hence, the experiments were used primarily to validate the NRC morphogenetic ice accretion model. The morphogenetic model is a discrete element, random walk model that emulates the motion and freezing of individual fluid elements on the accretion surface. After validating the numerical methodology against the wind tunnel experiments, the model was used to simulate ice formation under more realistic and general geometrical configurations and environmental conditions.Peer reviewed: YesNRC publication: Ye
Ultrafast X-ray spectroscopy of conical intersections
No full textOngoing developments in ultrafast x-ray sources offer powerful new means of probing the complex nonadiabatically coupled structural and electronic dynamics of photoexcited molecules. These non-Born-Oppenheimer effects are governed by general electronic degeneracies termed conical intersections, which play a key role, analogous to that of a transition state, in the electronic-nuclear dynamics of excited molecules. Using high-level ab initio quantum dynamics simulations, we studied time-resolved x-ray absorption (TRXAS) and photoelectron spectroscopy (TRXPS) of the prototypical unsaturated organic chromophore, ethylene, following excitation to its S2(\u3c0\u3c0 17) state. The TRXAS, in particular, is highly sensitive to all aspects of the ensuing dynamics. These x-ray spectroscopies provide a clear signature of the wave packet dynamics near conical intersections, related to charge localization effects driven by the nuclear dynamics. Given the ubiquity of charge localization in excited state dynamics, we believe that ultrafast x-ray spectroscopies offer a unique and powerful route to the direct observation of dynamics around conical intersections.Peer reviewed: YesNRC publication: Ye
Ultra-narrow linewidth quantum dot coherent comb lasers with self-injection feedback locking
No full textWe have used an external cavity self-injection feedback locking (SIFL) system to simultaneously reduce the optical linewidth of over 39 individual wavelength channels of an InAs/InP quantum dot (QD) coherent comb laser (CCL). Linewidth reduction from a few MHz to less than 200 kHz is observed. Measured phase noise spectra clearly indicate a significant decrease in phase noise in the frequency range above 2 kHz. The RF beating signal between two adjacent channels also shows a substantial reduction in 3-dB linewidth from 10 kHz to 300 Hz with the SIFL system, and a corresponding drop in baseline level ( 1227 dB to 1250 dB).Peer reviewed: YesNRC publication: Ye
Abstract 746: development of novel formats of anti-AXL ADCs
No full textAXL is a member of the Tyro3- AXL -Mer (TAM) receptor tyrosine kinase subfamily which has been associated with several cellular functions including growth, migration, aggregation, and anti-inflammation (Li Y et al., 2009) via activation through its ligand, Gas6. Originally identified as an oncogene in chronic myelogenous leukemia, expression of Axl has been reported to be upregulated in a variety of cancers including breast, gastric, prostate, ovarian, and lung. AXL expression has been shown to be negatively associated with patient survival and implicated in epithelial-to-mesenchymal transition, a process closely linked with invasive motility and metastasis of malignant cells. Several recent studies have reported that AXL is overexpressed during resistance to chemotherapy and other molecularly targeted therapies, as well as during hypoxia (Schoumacher M et al 2017). Consequently, Axl is promising therapeutic target for development into ADCs for the first or second line treatment of cancer. At the National Research Council (NRC) of Canada, we have selected mouse monoclonal (mAbs) or llama derived single domain antibodies (sdAbs) that are selective for the extracellular domain of human Axl and which have been shown to be internalized into Axl expressing cells for antibody drug conjugate (ADC) development using a surrogate ADC screen. These antibodies were also characterized based on their binding domains and ability to compete with Gas6, the extracellular ligand for Axl. A panel of Axl-specific ADCs was subsequently directly conjugated to maytansine, the microtubule disrupting agent through a noncleavable linker. Axl-DM1 ADCs were shown to efficiently induce cytotoxicity in vitro, in Axl expressing cells including breast (MDA-MB 231), lung (NCI-H292) and ovarian (SKOV3) cell lines with sub nM potencies achieved with both sdAb and conventional mAb-based ADCs. When tested in vivo using ovarian (SKOV3) and breast cancer (MDA-MB 231) xenograft models, Axl-DM1 ADCs were shown to have potent anti-tumor activity. Biparatopic antibodies (i.e. those which target two non-overlapping epitopes) directed against HER2 have been previously shown to induce target clustering and promote robust internalization, lysosomal trafficking, and degradation (LI JY et al 2016). Since these properties are important in the mechanism of action of ADCs, we have further tested anti-Axl antibodies in various configurations and have identified potent biparatopic antibodies for further development into ADCs.Peer reviewed: YesNRC publication: Ye
Development of a distributed building fault detection, diagnostic, and evaluation system
No full textThis paper introduces a distributed system for building fault detection, diagnostic, and evaluation (FDDE). The design of the distributed system aims to address computation and network limitations on a common commercial building automation system (BAS). This system also aims to be adaptable to different fault detection and fault diagnostics algorithms developed by other researchers. The fault evaluation aspect of the system provides quantitative impact metrics of the potential faults to the building operators. Probabilistic representations of faults and symptoms are used, and a continuous symptom severity value is developed to provide more granularity over the abnormal operation information. The proposed method is then tested with five fault cases simulated in EnergyPlus. Results show reduced false positive rate and enhanced fault belief when using a dynamic Bayesian network (DBN) over the conventional event-based Bayesian network (BN) used in fault diagnostics. Fault evaluation based on continuous symptom severity provides a reasonable quantitative reference for building operators to make informed decisions. This system will be further expanded with more fault detection algorithms and tested inside real buildings, and a framework will be made available for other researchers to develop upon.Peer reviewed: YesNRC publication: Ye
Challenges, mitigation strategies and perspectives in development of zinc-electrode materials and fabrication for rechargeable zinc\u2013air batteries
No full textAs a promising energy storage device, rechargeable zinc-air battery (RZAB) has drawn increasing attention because of its high energy density, cost-effectiveness, high safety, rich abundance of zinc, as well as environmental benignity. However, the widespread application of RZABs still face considerable challenges derived from zinc-electrodes, electrolytes, and air-electrodes. In this paper, a specific attention is given to RZAB zinc-electrode materials and fabrication with focus on the fundamental understanding of zinc-electrode reaction mechanisms, technical challenges, mitigation strategies, and perspectives. Particularly, the approaches to overcome the challenges are also presented and analyzed for facilitating the further reserach and development of RZABs.Peer reviewed: YesNRC publication: Ye
Structure of the LPS O-chain from Fusobacterium nucleatum strain ATCC 23726 containing a novel 5,7-diamino-3,5,7,9-tetradeoxy-l-gluco-non-2-ulosonic acid presumably having the d-glycero-l-gluco configuration
No full textFusobacterium nucleatum is an anaerobic bacterium found in the human mouth where it causes periodontitis. It was also found in colorectal cancer tissues and is linked with pregnancy complications, including pre-term and still births. Cell surface structures of the bacterium could be implicated in pathogenesis. Here we report the following structure of the lipopolysaccharide O-chain of a spontaneous streptomycin resistant (SmR) mutant of F. nucleatum strain ATCC 23726: -4-\u3b2-Non5Am7Ac-4-\u3b2-d-GlcNAcyl3NFoAN-3-\u3b2-d-FucNAc4N- where GlcNAcyl3NFoAN indicates 2,3-diamino-2,3-dideoxyglucuronic acid amide with Fo at N-3 being formyl and Acyl at N-2 being propanoyl ( 3c70%) or butanoyl ( 3c30%); Non5Am7Ac indicates 7-acetamido-5-acetimidoylamino-3,5,7,9-tetradeoxy-l-gluco-non-2-ulosonic acid presumably having the d-glycero-l-gluco configuration. To our knowledge, no l-gluco isomer of higher sugars of this class as well as no N-propanoyl or N-butanoyl group have so far been found in bacterial polysaccharides.Peer reviewed: YesNRC publication: Ye