National Research Council Canada
Recent publications
Encouraging disclosure is important for the patent system, yet the technical information in patent applications is often inadequate. We use algorithms from computational linguistics to quantify the effectiveness of disclosure in patent applications. Relying on the expectation that universities have more ability and incentive to disclose their inventions than corporations, we analyze 64 linguistic measures of patent applications, and show that university patents are more readable by 0.4 SD of a synthetic measure of readability. Results are robust to controlling for non-disclosure-related invention heterogeneity. The linguistic metrics are evaluated by a panel of “expert” student engineers and further examined by USPTO 112(a) – lack of disclosure – rejection. The ability to quantify disclosure opens new research paths and potentially facilitates improvement of disclosure.
Thermal radiation plays an important role in heat transfer process in oxy-fuel sooting flame (OFS). The accuracy of Full-Spectrum Correlated K-distribution (FSCK) methods with the original scheme (Modest and Zhang, 2002), the improved one (Cai and Modest, 2014), and the rank correlated one (Solovjov and Webb, 2018) is evaluated in two OFSs. As a comparison, two oxy-fuel non-sooting flames (OFNSs) are constructed as well. The performance of these three schemes in OFSs is basically consistent with that in OFNSs except for the original scheme in the high-soot-concentration regions. The original scheme displays larger errors than the other two schemes in the high-temperature regions, especially in the high-soot-concentration regions, though the error is quite small. The improved scheme provides excellent accuracy in the high-temperature regions, but significant errors in the low-temperature regions, which results in an overestimation of temperature by 38.8 K. The rank correlated scheme displays the best accuracy in both OFSs and OFNSs. Furthermore, the reference (or Planck) temperature has obvious impacts on the accuracy of original scheme, but has much weaker effects on the improved and rank correlated schemes.
Reproductive success hinges on precisely coordinated meiosis, yet our understanding of how structural rearrangements of chromatin and phase transitions during meiosis are transcriptionally regulated is limited. In crop plants, detailed analysis of the meiotic transcriptome could identify regulatory genes and epigenetic regulators that can be targeted to increase recombination rates and broaden genetic variation, as well as provide a resource for comparison amongst eukaryotes of different taxa to answer outstanding questions about meiosis. We conducted a meiotic stage‐specific analysis of messenger RNA (mRNA), small non‐coding RNA (sncRNA) and long intervening/intergenic non‐coding RNA (lincRNA) in wheat and revealed novel mechanisms of meiotic transcriptional regulation and meiosis‐specific transcripts. Amidst general repression of mRNA expression, significant enrichment of ncRNAs was identified during prophase I relative to vegetative cells. The core meiotic transcriptome comprised 9,309 meiosis‐specific transcripts, 48,134 previously unannotated meiotic transcripts, and many known and novel ncRNAs differentially expressed at specific stages. The abundant meiotic sncRNAs controlled the reprogramming of central metabolic pathways by targeting genes involved in photosynthesis, glycolysis, hormone biosynthesis, and cellular homeostasis, and lincRNAs enhanced the expression of nearby genes. Alternative splicing was not evident in this polyploid species, but isoforms were switched at phase transitions. The novel, stage‐specific regulatory controls uncovered here challenge the conventional understanding of this crucial biological process and provide a new resource of requisite knowledge for those aiming to directly modulate meiosis to improve crop plants. The wheat meiosis transcriptome dataset can be queried for genes of interest using an eFP browser located at http://bar.utoronto.ca/~asher/efp_wheat/cgi-bin/efpWeb.cgi?dataSource=Wheat_Meiosis.
A key resource in quantum-secured communication protocols are single photon emitters. For long-haul optical networks, it is imperative to use photons at wavelengths compatible with telecom single mode fibers. We demonstrate high purity single photon emission at 1.31 μm using deterministically positioned InP photonic waveguide nanowires containing single InAsP quantum dot-in-a-rod structures. At excitation rates that saturate the emission, we obtain a single photon collection efficiency at first lens of 27.6% and a probability of multiphoton emission of g(2)(0) = 0.021. We have also evaluated the performance of the source as a function of temperature. Multiphoton emission probability increases with temperature with values of 0.11, 0.34, and 0.57 at 77, 220 and 300 K, respectively, which is attributed to an overlap of temperature-broadened excitonic emission lines. These results are a promising step toward scalably fabricating telecom single photon emitters that operate under relaxed cooling requirements.
Crystal structures of camelid heavy-chain antibody variable domains (VHHs) bound to fragments of the combined repetitive oligopeptides domain of Clostridiodes difficile toxin A (TcdA) reveal that the C-terminus of VHH A20 was located 30 Å away from the N-terminus of VHH A26. Based on this observation, we generated a biparatopic fusion protein with A20 at the N-terminus, followed by a (GS)6 linker and A26 at the C-terminus. This A20-A26 fusion protein shows an improvement in binding affinity and a dramatic increase in TcdA neutralization potency (>330-fold [IC50]; ≥2,700-fold [IC99]) when compared to the unfused A20 and A26 VHHs. A20-A26 also shows much higher binding affinity and neutralization potency when compared to a series of control antibody constructs that include fusions of two A20 VHHs, fusions of two A26 VHHs, a biparatopic fusion with A26 at the N-terminus and A20 at the C-terminus (A26-A20), and actoxumab. In particular, A20-A26 displays a 310-fold (IC50) to 29,000-fold (IC99) higher neutralization potency than A26-A20. Size-exclusion chromatography-multiangle light scattering (SEC-MALS) analyses further reveal that A20-A26 binds to TcdA with 1:1 stoichiometry and simultaneous engagement of both A20 and A26 epitopes as expected based on the biparatopic design inspired by the crystal structures of TcdA bound to A20 and A26. In contrast, the control constructs show varied and heterogeneous binding modes. These results highlight the importance of molecular geometric constraints in generating highly potent antibody-based reagents capable of exploiting the simultaneous binding of more than one paratope to an antigen.
A reliable protocol for Agrobacterium-mediated genetic transformation of Lens culinaris Medik (lentil) was developed. Using cultivar Laird, the protocol yielded rooted shoots from an average of 6.8 independent events per hundred seeds. The protocol utilized longitudinal slices of embryo axes from imbibed mature seed as a starting explant and a plasmid containing a β-glucuronidase:neomycin phosphotransferase (gus:nptII) fusion gene in Agrobacterium strain EHA105. A series of four media, each with appropriate levels of kanamycin selection were identified and other factors tested included the optical density of the Agrobacterium suspension, and type and concentration of plant growth regulators. The expression of the gus reporter gene was visualized through histochemical staining, and further molecular analysis through PCR, qPCR, ddPCR and Southern hybridization confirmed transformation and provided copy number. The inserted genes were inherited into the T1 generation and chimaeras were not identified. The time from co-cultivation to the planting of rooted shoots ranged from 4 to 7 months, as transgenic clusters continue to produce additional clonal shoots.
Motivation: MHC Class I protein plays an important role in immunotherapy by presenting immunogenic peptides to anti-tumor immune cells. The repertoires of peptides for various MHC Class I proteins are distinct, which can be reflected by their diverse binding motifs. To characterize binding motifs for MHC Class I proteins, in vitro experiments have been conducted to screen peptides with high binding affinities to hundreds of given MHC Class I proteins. However, considering tens of thousands of known MHC Class I proteins, conducting in vitro experiments for extensive MHC proteins is infeasible, and thus a more efficient and scalable way to characterize binding motifs is needed. Results: We presented a de novo generation framework, coined PepPPO, to characterize binding motif for any given MHC Class I proteins via generating repertoires of peptides presented by them. PepPPO leverages a reinforcement learning (RL) agent with a mutation policy to mutate random input peptides into positive presented ones. Using PepPPO, we characterized binding motifs for around 10,000 known human MHC Class I proteins with and without experimental data. These computed motifs demonstrated high similarities with those derived from experimental data. In addition, we found that the motifs could be used for the rapid screening of neoantigens at a much lower time cost than previous deep-learning methods. Availability: The software can be found in https://github.com/minrq/pMHC. Supplementary information: Supplementary data are available at Bioinformatics online.
Embryonic stem cell (ESC) fate decisions are regulated by a complex circuitry that coordinates gene expression at multiple levels from chromatin to mRNA processing. Recently, ribosome biogenesis and translation have emerged as key pathways that efficiently control stem cell homeostasis, yet the underlying molecular mechanisms remain largely unknown. Here, we identified RSL24D1 as highly expressed in both mouse and human pluripotent stem cells. RSL24D1 is associated with nuclear pre-ribosomes and is required for the biogenesis of 60S subunits in mouse ESCs. Interestingly, RSL24D1 depletion significantly impairs global translation, particularly of key pluripotency factors and of components from the Polycomb Repressive Complex 2 (PRC2). While having a moderate impact on differentiation, RSL24D1 depletion significantly alters ESC self-renewal and lineage commitment choices. Altogether, these results demonstrate that RSL24D1-dependant ribosome biogenesis is both required to sustain the expression of pluripotent transcriptional programs and to silence PRC2-regulated developmental programs, which concertedly dictate ESC homeostasis. Pluripotency is coordinated at multiple levels of gene expression. Here the authors show that ribosome biogenesis is tightly regulated in embryonic stem cells (ESC) to control the translation of transcription and chromatin factors and dictate ESC fate.
Electrochemical conversion of CO2 (CO2R) offers a sustainable route for producing fuels and chemicals. Pd-based catalysts are effective for selective conversion of CO2 into formate at low overpotentials and CO/H2 at high overpotentials. Furthermore, Pd catalysts undergo morphology and phase structure transformations under reaction conditions that are not well understood. Herein, in-situ liquid phase transmission electron microscopy (LP-TEM) and select area diffraction (SAD) measurements under CO2R conditions is applied to track the morphology and Pd/PdHx phase interconversion as a function of electrode potential, respectively. Correlating in-situ characterization with electrochemical CO2R activity/selectivity measurements, density functional theory and micro-kinetic analyses, the change in Pd/PdHx catalyst selectivity from formate at low overpotentials towards CO/H2 at higher overpotentials is found to result from electrode potential-dependent thermodynamic changes in the reaction energetics and not morphological or phase structure changes, providing insight that can guide advanced understanding and design of improved performance catalysts.
Analytical chemistry is crucial for understanding the complex behavior observed for engineered nanomaterials (ENMs). A variety of analytical chemistry techniques and methodological approaches are used for isolation/purification and determination of the composition of pristine nanomaterials and for the detection, identification, and quantification of nanomaterials in nano-enabled consumer products and the complex matrices found in cosmetics, food, and environmental and biological samples. Adequate characterization of ENMs also requires physicochemical characterization of number of other properties, including size, shape, and structure. The requirement for assessment of a number of ENM properties frequently requires interdisciplinary approaches and multi-modal analysis methods. This technical report starts with an overview of ENMs definitions and classification, their properties, and analytical scenarios encountered with the analysis of both pristine nanomaterials and complex matrices containing different nanomaterials. An evaluation of the current status regarding nanomaterial identification and characterization for regulatory purposes and legislation, including emerging regulations and related scientific opinions, is provided. The technical report also presents a large and critical overview of the metrology of nanomaterials, including available reference materials and the development and validation of standardized methods that are currently available to address characterization and analysis challenges. The report focuses mainly on chemical analysis techniques and thus it is complementary to previous IUPAC technical reports focused on characterizing the physical parameters of ENMs and on nanotoxicology.
Introduction Early in the COVID-19 pandemic, reagent availability was not uniform, and infrastructure had to be urgently adapted to undertake COVID-19 surveillance. Methods Before the validation of centralized testing, two enzyme-linked immunosorbent assays (ELISA) were established independently at two decentralized sites using different reagents and instrumentation. We compared the results of these assays to assess the longitudinal humoral response of SARS-CoV-2-positive (i.e., PCR-confirmed), non-hospitalized individuals with mild to moderate symptoms, who had contracted SARSCoV-2 prior to the appearance of variants of concern in Québec, Canada. Results The two assays exhibited a high degree of concordance to identify seropositive individuals, thus validating the robustness of the methods. The results also confirmed that serum immunoglobulins persist ≥ 6 months post-infection among non-hospitalized adults and that the antibodies elicited by infection cross-reacted with the antigens from P.1 (Gamma) and B.1.617.2 (Delta) variants of concern. Discussion Together, these results demonstrate that immune surveillance assays can be rapidly and reliably established when centralized testing is not available or not yet validated, allowing for robust immune surveillance.
Background Chimeric antigen receptor T cell therapy (CAR-T) represents a promising and exciting new therapy for hematologic malignancies, where prognosis for relapsed/refractory patients remains poor. Encouraging results from clinical trials have often been tempered by heterogeneity in response to treatment among patients, as well as safety concerns including cytokine release syndrome. The identification of specific patient or treatment-specific factors underlying this heterogeneity may provide the key to the long-term sustainability of this complex and expensive therapy. An individual patient data meta-analysis (IPMDA) may provide potential explanations for the high degree of heterogeneity. Therefore, our objective is to perform a systematic review and IPDMA of CAR-T cell therapy in patients with hematologic malignancies to explore potential effect modifiers of CAR-T cell therapy. Methods and analysis We will search MEDLINE, Embase, and the Cochrane Central Register of Controlled Clinical Trials. Studies will be screened in duplicate at the abstract level, then at the full-text level by two independent reviewers. We will include any prospective clinical trial of CAR-T cell therapy in patients with hematologic malignancies. Our primary outcome is complete response, while secondary outcomes of interest include overall response, progression-free survival, overall survival, and safety. IPD will be collected from each included trial and, in the case of missing data, corresponding authors/study sponsors will be contacted. Standard aggregate meta-analyses will be performed, followed by the IPD meta-analysis using a one-stage approach. A modified Institute of Health Economics tool will be used to evaluate the risk of bias of included studies. Ethics and dissemination Identifying characteristics that may act as modifiers of CAR-T cell efficacy is of paramount importance and can help shape future clinical trials in the field. Results from this study will be submitted for publication in a peer-reviewed scientific journal, presented at relevant conferences and shared with relevant stakeholders.
Pyramiding multiple resistant genes has been proposed as the most effective way to control wheat rust diseases globally. Identifying the most effective pyramids is challenged by the large pool of rust resistance genes, and limited information about their mechanisms of resistance and interactions. Here, using a high-density genetic map, a double haploid population, and multi-rust field testing, we aimed to systematically characterize the most effective gene pyramids for rust resistance from the durable multi-rust resistant CIMMYT cultivar, Parula. We revealed the Parula resistance gene pyramid contains Lr34/Yr18/Sr57 (Lr34), Lr46/Yr29/Sr58 (Lr46), Lr27/Yr30/Sr2 (Sr2) and Lr68. The efficacy, magnitude of effect and interactions with each other varied for the three rust diseases. A subpopulation mapping approach was applied to characterize the complex interactions of the resistance genes by controlling for the effect of Lr34. Using this approach, we found Lr34 and Lr68 have a strong additive effect for leaf rust, while no additive effects were observed for any rusts between Lr34 and Lr46. Lr34 combined synergistically with Sr12 from Thatcher for stem rust, while the additive effect of Lr34 and Sr2 was dependent on the type of rust and environment. Two novel leaf rust QTL from Parula were identified in this study, a stable QTL QLr-7BS, and QLr-5AS, which showed Lr34 dependent expression. With these findings, we propose combining 2–3 high value genes from Canadian wheat (e.g. Sr12 from Thatcher) with a foundational multi-APR cassette for desirable and durable resistance to all three rusts in Canadian wheat.
Chitosan is typically produced by the deacetylation of biopolymer chitin. Its molecular weight (Mw) is a function of the chitin source and the deacetylation conditions. It remains a challenge to both control the Mw of chitosan and obtain good polydispersity, essential for optimal function of chitosan in different applications. This study explores the use of mechanochemistry and aging as effective methods towards the controlled reduction of the Mw of commercial high Mw chitosan (HMwChs) with phosphoric acid where Mw was measured by gel permeation chromatography (GPC). In comparison to conventional solution-based methods, this new mechanochemical process features improved process mass intensity in comparison to conventional techniques and affords low Mw chitosan (LMwChs) samples in a range of 200 to as low as 19.5 kDa, with a polydispersity of 1.8.
We show a simple yet effective method that can be used to characterize the per pixel quantum efficiency and temporal resolution of a single photon event camera for quantum imaging applications. Utilizing photon pairs generated through spontaneous parametric down-conversion, the detection efficiency of each pixel, and the temporal resolution of the system, are extracted through coincidence measurements. We use this method to evaluate the TPX3CAM, with appended image intensifier, and measure an average efficiency of 7.4±2% and a temporal resolution of 7.3 ns. Furthermore, this technique reveals important error mechanisms that can occur in post-processing. We expect that this technique, and elements therein, will be useful to characterise other quantum imaging systems.
In this announcement, we present the set of putative terpene synthase (TS) gene fragments detected in a subseafloor sediment sample collected off Shimokita Peninsula, Japan. This data set contains sequences with 72 to 100% identity to TS from actinobacteria and cyanobacteria.
Recent high-level theoretical calculations predict a mild temperature dependence for HO2 + HO2 inconsistent with state-of-the-art experimental determinations that upheld the stronger temperature dependence observed in early experiments. Via MultiScale Informatics analysis of the theoretical and experimental data, we identified an alternative interpretation of the raw experimental data that uses HO2 + HO2 rate constants nearly identical to theoretical predictions─implying that the theoretical and experimental data are actually consistent, at least when considering the raw data from experimental studies. Similar analyses of typical signals from low-temperature experiments indicate that an HOOOOH intermediate─identified by recent theory but absent from earlier interpretations─yields modest effects that are smaller than, but may have contributed to, the scatter in data among different experiments. More generally, the findings demonstrate that modern chemical theories and experiments have progressed to a point where meaningful comparison requires joint consideration of their data simultaneously.
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