Exposing the Unseen: Exposure Time Emulation for Offline Benchmarking of Vision Algorithms

Visual Odometry (VO) is one of the fundamental tasks in computer vision for robotics. However, its performance is deeply affected by High Dynamic Range (HDR) scenes, omnipresent outdoor. While new Automatic-Exposure (AE) approaches to mitigate this have appeared, their comparison in a reproducible manner is problematic. This stems from the fact that the behavior of AE depends on the environment, and it affects the image acquisition process. Consequently, AE has traditionally only been benchmarked in an online manner, making the experiments non-reproducible. To solve this, we propose a new methodology based on an emulator that can generate images at any exposure time. It leverages BorealHDR, a unique multi-exposure stereo dataset collected over 8.4 km, on 50 trajectories with challenging illumination conditions. Moreover, it contains pose ground truth for each image and a global 3D map, based on lidar data. We show that using these images acquired at different exposure times, we can emulate realistic images keeping a Root-Mean-Square Error (RMSE) below 1.78 % compared to ground truth images. To demonstrate the practicality of our approach for offline benchmarking, we compared three state-of-the-art AE algorithms on key elements of Visual Simultaneous Localization And Mapping (VSLAM) pipeline, against four baselines. Consequently, reproducible evaluation of AE is now possible, speeding up the development of future approaches. Our code and dataset are available online at this link: https://github.com/norlab-ulaval/BorealHDRComment: 6 pages, 6 figures, submitted to 2024 IEEE International Conference on Robotics and Automation (ICRA 2024

Direct inscription of on-surface waveguides in polymers using a mid-ir fiber laser

A detailed study of photo-inscribed optical waveguides in PMMA and polycarbonate using a mid-IR laser is presented. The wavelength of the laser is tuned near the absorption peaks of stretching C-H molecular bonds and the focused beam is scanned onto the surface of planar polymer samples. For the first time, we report the formation of optical waveguides in both polymers through resonant absorption of the laser beam. The optical properties of the waveguides were thoroughly assessed. An elliptic Gaussian mode is guided at the surface of both polymers. Insertion losses of 3.1 dB for a 30 mm long on-surface waveguide inscribed in PMMA were recorded. Such waveguides can interact with the external medium through evanescent coupling. As a proof of concept, the surface waveguides are used as highly sensitive refractometric sensors. An attenuation dynamical range of 35 dB was obtained for a liquid that matches the index of the PMMA substrate. Our results pave the way for large scale manufacturing of low cost biocompatible photonic devices

A tagged parathyroid hormone derivative as a carrier of antibody cargoes transported by the G protein coupled PTH1 receptor

Based on the known fact that the parathyroid hormone (PTH) might be extended at its C-terminus with biotechnological protein cargoes, a vector directing the secretion of PTH1–84 C-terminally fused with the antigenic epitope myc (PTH-myc) was exploited. The functional properties and potential of this analog for imaging PTH1R-expressing cells were examined. The PTH-myc construct was recombinantly produced as a conditioned medium (CM) of transfected HEK 293a cells (typical concentrations of 187 nM estimated with ELISAs for PTH). PTH-myc CM induced cyclic AMP formations (10 min), with a minor loss of potency relative to authentic PTH1–84, and c-Fos expression (1–3 h). Treatment of recipient HEK 293a cells transiently expressing PTH1R with PTH-myc CM (supplemented with a fluorescent monoclonal anti-myc tag antibody, either 4A6 or 9E10) allowed the labeling of endosomal structures positive for Rab5 and/or for β-arrestin1 (microscopy, cytofluorometry). Authentic PTH was inactive in this respect, ruling out a non-specific form of endocytosis like pinocytosis. Using a horseradish peroxidase-conjugated secondary antibody, the endocytosis of the PTH-myc-based antibody complex by endogenous PTH1R was evidenced in MG-63 osteoblastoid cells. The secreted construct PTH-myc represents a bona fide agonist that supports the feasibility of transporting cargoes of considerable molecular weight inside cells using arrestin and Rab5-mediated PTH1R endocytosis. PTH-myc is also transported into cells that express PTH1R at a physiological level. Such tagged peptide hormones may be part of a cancer chemotherapy scheme exploiting a modular cytotoxic secondary antibody and the receptor repertoire expressed in a given tumor

Nonlinear increase, invisibility, and sign inversion of a localized fs-laser-induced refractive index change in crystals and glasses

Multiphoton absorption via ultrafast laser focusing is the only technology that allows a three-dimensional structural modification of transparent materials. However, the magnitude of the refractive index change is rather limited, preventing the technology from being a tool of choice for the manufacture of compact photonic integrated circuits. We propose to address this issue by employing a femtosecond-laser-induced electronic band-gap shift (FLIBGS), which has an exponential impact on the refractive index change for propagating wavelengths approaching the material electronic resonance, as predicted by the Kramers–Kronig relations. Supported by theoretical calculations, based on a modified Sellmeier equation, the Tauc law, and waveguide bend loss calculations, we experimentally show that several applications could take advantage of this phenomenon. First, we demonstrate waveguide bends down to a submillimeter radius, which is of great interest for higher-density integration of fs-laser-written quantum and photonic circuits. We also demonstrate that the refractive index contrast can be switched from negative to positive, allowing direct waveguide inscription in crystals. Finally, the effect of the FLIBGS can compensate for the fs-laser-induced negative refractive index change, resulting in a zero refractive index change at specific wavelengths, paving the way for new invisibility applications

Removing inter-subject technical variability in magnetic resonance imaging studies

Magnetic resonance imaging (MRI) intensities are acquired in arbitrary units, making scans non-comparable across sites and between subjects. Intensity normalization is a first step for the improvement of comparability of the images across subjects. However, we show that unwanted inter-scan variability associated with imaging site, scanner effect and other technical artifacts is still present after standard intensity normalization in large multi-site neuroimaging studies. We propose RAVEL (Removal of Artificial Voxel Effect by Linear regression), a tool to remove residual technical variability after intensity normalization. As proposed by SVA and RUV [Leek and Storey, 2007, 2008, Gagnon-Bartsch and Speed, 2012], two batch effect correction tools largely used in genomics, we decompose the voxel intensities of images registered to a template into a biological component and an unwanted variation component. The unwanted variation component is estimated from a control region obtained from the cerebrospinal fluid (CSF), where intensities are known to be unassociated with disease status and other clinical covariates. We perform a singular value decomposition (SVD) of the control voxels to estimate factors of unwanted variation. We then estimate the unwanted factors using linear regression for every voxel of the brain and take the residuals as the RAVEL-corrected intensities. We assess the performance of RAVEL using T1-weighted (T1-w) images from more than 900 subjects with Alzheimer’s disease (AD) and mild cognitive impairment (MCI), as well as healthy controls from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. We compare RAVEL to intensity-normalization-only methods, histogram matching, and White Stripe. We show that RAVEL performs best at improving the replicability of the brain regions that are empirically found to be most associated with AD, and that these regions are significantly more present in structures impacted by AD (hippocampus, amygdala, parahippocampal gyrus, enthorinal area and fornix stria terminals). In addition, we show that the RAVEL-corrected intensities have the best performance in distinguishing between MCI subjects and healthy subjects by using the mean hippocampal intensity (AUC=67%), a marked improvement compared to results from intensity normalization alone (AUC=63% and 59% for histogram matching and White Stripe, respectively). RAVEL is generalizable to many imaging modalities, and shows promise for longitudinal studies. Additionally, because the choice of the control region is left to the user, RAVEL can be applied in studies of many brain disorders

Bifunctional ligands of the bradykinin B2 and B1 receptors : an exercise in peptide hormone plasticity

Kinins are the small and fragile hydrophilic peptides related to bradykinin (BK) and derived from circulating kininogens via the action of kallikreins. Kinins bind to the preformed and widely distributed B2 receptor (B2R) and to the inducible B1 receptor (B1R). B2Rs and B1Rs are related G protein coupled receptors that possess natural agonist ligands of nanomolar affinity (BK and Lys BK for B2Rs, Lys-des-Arg9-BK for B1R). Decades of structure-activity exploration have resulted in the production of peptide analogs that are antagonists, one of which is clinically used (the B2R antagonist icatibant), and also non-peptide ligands for both receptor subtypes. The modification of kinin receptor ligands has made them resistant to extracellular or endosomal peptidases and/or produced bifunctional ligands, defined as agonist or antagonist peptide ligands conjugated with a chemical fluorophore (emitting in the whole spectrum, from the infrared to the ultraviolet), a drug-like moiety, an epitope, an isotope chelator/carrier, a cleavable sequence (thus forming a pro-drug) and even a fused protein. Dual molecular targets for specific modified peptides may be a source of side effects or of medically exploitable benefits. Biotechnological protein ligands for either receptor subtype have been produced: they are enhanced green fluorescent protein or the engineered peroxidase APEX2 fused to an agonist kinin sequence at their C-terminal terminus. Antibodies endowed with pharmacological actions (agonist, antagonist) at B2R have been reported, though not monoclonal antibodies. These findings define classes of alternative ligands of the kinin receptor of potential therapeutic and diagnostic value

A Novel Nonpeptide Antagonist of the Kinin B 1 Receptor: Effects at the Rabbit Receptor

ABSTRACT The kinin B 1 receptor (B 1 R) has attracted interest as a potential therapeutic target because this inducible G protein-coupled receptor is involved in sustained inflammation and inflammatory pain production. is a high-affinity nonpeptide antagonist for the human B 1 R, but it is potent at the rabbit B 1 R as well: its K i value for the inhibition of [ The kinin B 1 receptor (B 1 R) is a G protein-coupled receptor selectively stimulated by sequences related to bradykinin (BK) but not by BK itself. Instead, des-Arg 9 -BK, Lys-BK (kallidin) and Lys-des-Arg 9 -BK (des-Arg 1

Roadmap for the use of base editors to decipher drug mechanism of action

CRISPR base editors are powerful tools for large-scale mutagenesis studies. This kind of approach can elucidate the mechanism of action of compounds, a key process in drug discovery. Here, we explore the utility of base editors in an early drug discovery context focusing on G-protein coupled receptors. A pooled mutagenesis screening framework was set up based on a modified version of the CRISPR-X base editor system. We determine optimized experimental conditions for mutagenesis where sgRNAs are delivered by cell transfection or viral infection over extended time periods (>14 days), resulting in high mutagenesis produced in a short region located at -4/+8 nucleotides with respect to the sgRNA match. The β2 Adrenergic Receptor (B2AR) was targeted in this way employing a 6xCRE-mCherry reporter system to monitor its response to isoproterenol. The results of our screening indicate that residue 184 of B2AR is crucial for its activation. Based on our experience, we outline the crucial points to consider when designing and performing CRISPR-based pooled mutagenesis screening, including the typical technical hurdles encountered when studying compound pharmacolog

Bradykinin receptors : agonists, antagonists, expression, signaling and adaptation to sustained stimulation

Bradykinin-related peptides, the kinins, are blood-derived peptides that stimulate 2 G protein–coupled receptors, the B1 and B2 receptors (B1R, B2R). The pharmacologic and molecular identities of these 2 receptor subtypes will be succinctly reviewed, with emphasis on drug development, receptor expression, signaling, and adaptation to persistent stimulation. Peptide and nonpeptide antagonists and fluorescent ligands have been produced for each receptor. The B2R is widely and constitutively expressed in mammalian tissues, whereas the B1R is mostly inducible under the effect of cytokines during infection and immunopathology. Both receptor subtypes mediate the vascular aspects of inflammation (vasodilation, edema formation). On this basis, icatibant, a peptide antagonist of the B2R, is approved in the management of hereditary angioedema attacks. Other clinical applications are still elusive despite the maturity of the medicinal chemistry efforts applied to kinin receptors. While both receptor subtypes are mainly coupled to the Gq protein and related second messengers, the B2R is temporarily desensitized by a cycle of phosphorylation/endocytosis followed by recycling, whereas the nonphosphorylable B1R is relatively resistant to desensitization and translocated to caveolae on activation

A nanoparticle ink allowing the high precision visualization of tissue engineered scaffolds by MRI

Hydrogels are widely used as cell scaffolds in several biomedical applications. Once implanted in vivo, cell scaffolds must often be visualized, and monitored overtime. However, cell scaffolds appear poorly contrasted in most biomedical imaging modalities such as magnetic resonance imaging (MRI). MRI is the imaging technique of choice for high-resolution visualization of low-density, water-rich tissues. Attempts to enhance hydrogel contrast in MRI are performed with “negative” contrast agents that produce several image artifacts impeding the delineation of the implant’s contours. In this study, a magnetic ink based on ultra-small iron oxide nanoparticles (USPIONs; <5 nm diameter cores) is developed and integrated into biocompatible alginate hydrogel used in cell scaffolding applications. Relaxometric properties of the magnetic hydrogel are measured, as well as biocompatibility and MR-visibility (T1-weighted mode; in vitro and in vivo). A 2-week MR follow-up study is performed in the mouse model, demonstrating no image artifacts, and the retention of “positive” contrast overtime, which allows very precise delineation of tissue grafts with MRI. Finally, a 3D-contouring procedure developed to facilitate graft delineation and geometrical conformity assessment is applied on an inverted template alginate pore network. This proof-of-concept establishes the possibility to reveal precisely engineered hydrogel structures using this USPIONs ink high-visibility approach