57949 research outputs found
Sort by
Evaluation of a noncanonical Cys40\u2010Cys55 disulfide linkage for stabilization of single\u2010domain antibodies
Incorporation of noncanonical disulfide linkages into single\u2010domain antibodies (sdAbs) has been shown to enhance thermostability and other properties. Here, we evaluated the effects of introducing a novel disulfide linkage formed between Cys residues at IMGT positions 40 and 55 on the melting temperatures (T ms), reversibility of thermal unfolding, solubility, and antigen\u2010binding affinities of three types of sdAbs (VHH, VH, and VL domains). The Cys40\u2010Cys55 disulfide linkage was tolerated by 9/9 VHHs, 12/12 VHs, and 2/11 VLs tested and its formation was confirmed by mass spectrometry. Using circular dichroism, we found that the Cys40\u2010Cys55 disulfide linkage increased sdAb T m by an average of 10.0\ub0C (range: 0\u201321.8\ub0C). However, enhanced thermostability came at the cost of a partial loss of refolding ability upon thermal denaturation as well as, for some sdAbs, significantly decreased solubility and antigen\u2010binding affinity. Thus, Cys40/Cys55 can be added to the panel of known locations for introducing stabilizing noncanonical disulfide linkages into antibody variable domains, although its effects should be tested empirically for individual sdAbs.Peer reviewed: YesNRC publication: Ye
Flooding related consequences of climate change on Canadian cities and flow regulation infrastructure
This study discusses the flooding related consequences of climate change on most populous Canadian cities and flow regulation infrastructure (FRI). The discussion is based on the aggregated results of historical and projected future flooding frequencies and flood timing as generated by Canada-wide hydrodynamic modelling in a previous study. Impact assessment on 100 most populous Canadian cities indicate that future flooding frequencies in some of the most populous cities such as Toronto and Montreal can be expected to increase from 100 (250) years to 15 (22) years by the end of the 21st century making these cities highest at risk to projected changes in flooding frequencies as a consequence of climate change. Overall 40\u201360% of the analyzed cities are found to be associated with future increases in flooding frequencies and associated increases in flood hazard and flood risk. The flooding related impacts of climate change on 1072 FRIs located across Canada are assessed both in terms of projected changes in future flooding frequencies and changes in flood timings. Results suggest that 40\u201350% of the FRIs especially those located in southern Ontario, western coastal regions, and northern regions of Canada can be expected to experience future increases in flooding frequencies. FRIs located in many of these regions are also projected to experience future changes in flood timing underlining that operating rules for those FRIs may need to be reassessed to make them resilient to changing climate.Peer reviewed: YesNRC publication: Ye
Characterization of black carbon particles generated by a propane-fueled miniature inverted soot generator
The miniature inverted soot generator is a novel soot particle generator, capable of producing black carbon (BC) particles with a wide range of properties. The main advantages of this device are its portability, simplicity, low fuel consumption, and relatively low cost compared to other soot generators. In this study, the performance of the miniature inverted soot generator was evaluated using propane as the fuel over a range of air and fuel flow rates. The stability and repeatability of the soot generator to produce BC particles of controlled size distribution, and number and mass concentration was demonstrated. Furthermore, optical absorption, single scattering albedo (SSA), and elemental carbon (EC) and organic carbon (OC) concentrations of the generated particles were measured. When fueled with propane, the miniature inverted soot generator was capable of repeatedly generating particles with average mode mobility diameter ranging from 140\u202fnm to 200\u202fnm, number concentrations 3c4\u202f
7\u202f10\u2076\u2013 3c2.7\u202f
7\u202f10\u2077 #/cm\ub3, and mass concentrations 3c8\u2013 3c140\u202fmg/m\ub3. For many of the investigated operating conditions, the elemental to total carbon ratio (EC/TC) of the generated soot particles was greater than 90%. The mass absorption cross section of generated particles ranged from 3 to 5\u202fm\ub2/g at a wavelength of 870\u202fnm. The results obtained from this study indicate that the miniature inverted soot generator is ideal for producing BC particles with high EC fraction, which can be used as calibration aerosol for BC diagnostic instruments.Peer reviewed: YesNRC publication: Ye
Ultra-wideband Ge-rich silicon germanium mid-infrared polarization rotator with mode hybridization flattening
In this work we investigate the implementation of ultra-wideband polarization rotator in the mid-infrared spectral region. A new design method of the rotation section is proposed, yielding a polarization rotator with an extinction ratio of at least 15 dB in a wavelength range of 2 \ub5m. For a spectral range wider than 3.8 \ub5m, an extinction ratio of at least 10 dB is achieved for this design. The device is 1660 \ub5m long and the associated insertion loss is below 1.2 dB on the full operational wavelength range. The influence of geometrical parameters with respect to the design method to obtain such a broadband behavior is discussed. Finally, to increase the tolerance to fabrication errors, a tapered rotator design is proposed. Such a device can support up to \ub1 100 nm fabrication errors and still guarantees remarkable broadband behavior. To the best of our knowledge, this is the first time an integrated polarization rotator is designed to operate for the wavelength range of 4 to 9 \ub5m with a bandwidth exceeding 2 \ub5m.Peer reviewed: YesNRC publication: Ye
Elucidating the role of Kelpak\uae on the growth, phytohormone composition, and phenolic acids in macronutrient-stressed Ceratotheca triloba
We evaluated the role of Kelpak\uae on growth, nutritional content, phytohormones, and phenolic acids in the angiosperm Ceratotheca triloba (Bernh.) Hook.f. grown under macronutrient-deficient conditions. Seeds were germinated in the greenhouse and established seedlings were treated with 50% Hoagland\u2019s solution (50% HS) or nutrient-deficient solutions lacking one of the following: nitrogen (-N), phosphorus (-P), potassium (-K), which were either treated with or without Kelpak\uae (control). After 4 months of growth, macronutrient deficiency severely reduced growth and nutritional composition in plants. Nevertheless, the detrimental effects of insufficient macronutrient supply on growth were ameliorated with the application of Kelpak\uae, with a fourfold (-N), threefold (-P), and twofold (-K) increase in leaf and root fresh weight. Mineral and carbohydrate levels increased in plants deprived of N and P when Kelpak\uae was applied in the different soils. Macronutrient stress (N, P, K) increased phytohormone production in C. triloba more than in 50% HS-treated plants. The phytohormone content in macronutrient-deficient leaves was further enhanced with the application of Kelpak\uae. On the contrary, application of Kelpak\uae suppressed the production of phenolic acids in 50% HS, -N, and -K-treated plants when compared to the control treatments. The interaction between macronutrient deficiency and Kelpak\uae application played an important role in the regulation of phytohormone and phenolic acid concentration in C. triloba. The current findings demonstrated the potential of Kelpak\uae as an efficient biostimulant that enhances nutrient uptake for improved growth and biochemicals in C. triloba under macronutrient stress condition.Peer reviewed: YesNRC publication: Ye
Navigating through complex photonic design space using machine learning methods
The performance and functionality of integrated photonic devices can be enhanced by using complex structures controlled by a large number of design variables. However, the optimization of such high-dimensional structures is challenging, often limiting their realization. Global optimization algorithms and artificial neural networks are increasingly used to tackle these problems. Although these are exciting new developments, the outcome is a single optimized design meeting particular performance objectives selected upfront. The influences of the various design parameters remain hidden. Here we report on our strategy of using machine learning pattern recognition techniques to create a methodology for building the global performance map of a high-dimensional design space. As an example and demonstration, we study the design of a vertical grating coupler consisting of silicon and subwavelength metamaterial segments. We show how the relationship between designs with comparable primary performance can be clearly revealed by identifying the minimum number of characterizing parameters that defines the subspace of good designs, significantly scaling down the complexity of the problem. Moreover, the subspace can be identified using only a small number of good design solutions. We reveal design areas with comparable fiber coupling efficiency but with significant differences in other performance criteria, such as back-reflections, tolerance to fabrication uncertainty and minimum feature size. This novel approach provides the designer with a global perspective of the design space, enabling informed decisions based on the relative priorities of all relevant performance specifications and figures-of-merits for a particular application. Insights from the mapping exercise also inspired new design structures with enhanced characteristics.Peer reviewed: YesNRC publication: Ye
Advances in novel vaccines for foot and mouth disease: focus on recombinant empty capsids
Foot and mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, which causes severe economic losses in the livestock industry. Currently available vaccines are based on inactivated FMD virus (FMDV). Although inactivated virus vaccines have proved to be effective in FMD control, they have a number of disadvantages, including the need for high bio-containment production facilities and the lack of induction of immunological memory. Novel FMD vaccines based on the use of recombinant empty capsids have shown promising results. These recombinant empty capsids are attractive candidates because they avoid the use of virus in the production facilities but conserve its complete repertoire of conformational epitopes. However, many of these recombinant empty capsids require time-consuming procedures that are difficult to scale up. Achieving production of a novel and efficient FMD vaccine requires not only immunogenic antigens, but also industrially relevant processes. This review intends to summarize and compare the different strategies already published for the production of FMDV recombinant empty capsids, focusing on large-scale production.Peer reviewed: YesNRC publication: Ye
Bragg filter bandwidth engineering in subwavelength grating metamaterial waveguides
Bragg gratings are fundamental building blocks for integrated photonic circuits. In the high-index contrast silicon-on-insulator material platform, it is challenging to accurately control the grating strength and achieve narrow spectral bandwidths. Here we demonstrate a novel Bragg grating geometry utilizing a silicon subwavelength grating (SWG) waveguide with evanescently coupled periodic Bragg loading segments placed outside the SWG core. We report experimental 3 dB filter bandwidths in a range from 8 nm to 150 pm by adjusting the distance of the Bragg loading segments from the core and the relative phase shift of the segments on the two sides of the waveguide, with a structure that has a minimum feature size of 100 nm.Peer reviewed: YesNRC publication: Ye
Design of an analysis guide for user-centered process mining projects
Process mining provides a set of techniques capable of analyzing event logs stored in information systems in order to improve these processes. The procedures available to carry out process mining projects have some limitations, some of these are: lack of clarity in the presentation and visualization of the results, limited user participation in the project stages, and lack of understanding of the characteristics of the context. The objective of this research is to make a projection of a process mining guide for the development of user-centered projects. A descriptive approach was followed to review the state of the art and to analyze the current procedures that are used for developing process mining projects and the principles of user-centered design. As a result, a process mining guide is proposed that integrates principles of user-centered design. It was evidenced that the user-centered design is fundamental for satisfactory development of certain products, systems or services.Peer reviewed: YesNRC publication: Ye
Genetics behind the biosynthesis of nonulosonic acid-containing lipooligosaccharides in Campylobacter coli
Campylobacter jejuni and Campylobacter coli are the most common causes of bacterial gastroenteritis in the world. Ganglioside mimicry by C. jejuni lipooligosaccharide (LOS) is the triggering factor of Guillain-Barr\ue9 syndrome (GBS), an acute polyneuropathy. Sialyltransferases from glycosyltransferase family 42 (GT-42) are essential for the expression of ganglioside mimics in C. jejuni. Recently, two novel GT-42 genes, cstIV and cstV, have been identified in C. coli. Despite being present in 3c11% of currently available C. coli genomes, the biological role of cstIV and cstV is unknown. In the present investigation, mutation studies with two strains expressing either cstIV or cstV were performed and mass spectrometry was used to investigate differences in the chemical composition of LOS. Attempts were made to identify donor and acceptor molecules using in vitro activity tests with recombinant GT-42 enzymes. Here we show that CstIV and CstV are involved in C. coli LOS biosynthesis. In particular, cstV is associated with LOS sialylation, while cstIV is linked to the addition of a diacetylated nonulosonic acid residue.Peer reviewed: YesNRC publication: Ye