Placental Homing Peptide-microRNA Inhibitor Conjugates For Targeted Enhancement Of Intrinsic Placental Growth Signalling

Suboptimal placental growth and development are the underlying cause of many pregnancy complications. No treatments are available, primarily due to the risk of causing fetal teratogenicity. microRNAs (miRNAs) are short, non-coding RNA sequences that regulate multiple downstream genes; miR-145 and miR675 have previously been identified as negative regulators of placental growth. In this proof of principle study, we explored the feasibility of delivering miRNA inhibitors to the placentas of pregnant mice and developed novel placental homing peptide-microRNA inhibitor conjugates for targeted enhancement of intrinsic placental growth signalling. Scrambled-, miR-145- or miR-675 inhibitor sequences were synthesised from peptide nucleic acids and conjugated to the placental homing peptide CCGKRK. Intravenous administration of the miR-145- and miR-675 conjugates to pregnant C57BL/6J mice significantly increased fetal and placental weights compared to controls; the miR-675 conjugate significantly reduced placental miR-675 expression. When applied to human first trimester placental explants, the miR-145 conjugate significantly reduced placental miR-145 expression, and both conjugates induced significant enhancement of cytotrophoblast proliferation; no effect was observed in term placental explants. This study demonstrates that homing peptide-miRNA inhibitor conjugates can be exploited to promote placental growth; these novel therapeutics may represent an innovative strategy for targeted treatment of compromised placental development

Cascaded Filtering Using the Sigma Point Transformation (Extended Version)

It is often convenient to separate a state estimation task into smaller "local" tasks, where each local estimator estimates a subset of the overall system state. However, neglecting cross-covariance terms between state estimates can result in overconfident estimates, which can ultimately degrade the accuracy of the estimator. Common cascaded filtering techniques focus on the problem of modelling cross-covariances when the local estimators share a common state vector. This letter introduces a novel cascaded and decentralized filtering approach that approximates the cross-covariances when the local estimators consider distinct state vectors. The proposed estimator is validated in simulations and in experiments on a three-dimensional attitude and position estimation problem. The proposed approach is compared to a naive cascaded filtering approach that neglects cross-covariance terms, a sigma point-based Covariance Intersection filter, and a full-state filter. In both simulations and experiments, the proposed filter outperforms the naive and the Covariance Intersection filters, while performing comparatively to the full-state filter.Comment: This is an extended version of the original letter to be published in the IEEE Robotics and Automation Letter

Reducing Two-Way Ranging Variance by Signal-Timing Optimization

Time-of-flight-based range measurements among transceivers with different clocks requires ranging protocols that accommodate for the varying rates of the clocks. Double-sided two-way ranging (DS-TWR) has recently been widely adopted as a standard protocol due to its accuracy; however, the precision of DS-TWR has not been clearly addressed. In this paper, an analytical model of the variance of DS-TWR is derived as a function of the user-programmed response delays. Consequently, this allows formulating an optimization problem over the response delays in order to maximize the information gained from range measurements by addressing the effect of varying the response delays on the precision and frequency of the measurements. The derived analytical variance model and proposed optimization formulation are validated experimentally with 2 ranging UWB transceivers, where 29 million range measurements are collected.Comment: 5 pages, 4 figures, submitted to 2023 International Conference on Acoustics, Speech and Signal Processing (ICASSP

Paragraph-level Commonsense Transformers with Recurrent Memory

Human understanding of narrative texts requires making commonsense inferences beyond what is stated explicitly in the text. A recent model, COMET, can generate such implicit commonsense inferences along several dimensions such as pre- and post-conditions, motivations, and mental states of the participants. However, COMET was trained on commonsense inferences of short phrases, and is therefore discourse-agnostic. When presented with each sentence of a multi-sentence narrative, it might generate inferences that are inconsistent with the rest of the narrative. We present the task of discourse-aware commonsense inference. Given a sentence within a narrative, the goal is to generate commonsense inferences along predefined dimensions, while maintaining coherence with the rest of the narrative. Such large-scale paragraph-level annotation is hard to get and costly, so we use available sentence-level annotations to efficiently and automatically construct a distantly supervised corpus. Using this corpus, we train PARA-COMET, a discourse-aware model that incorporates paragraph-level information to generate coherent commonsense inferences from narratives. PARA-COMET captures both semantic knowledge pertaining to prior world knowledge, and episodic knowledge involving how current events relate to prior and future events in a narrative. Our results show that PARA-COMET outperforms the sentence-level baselines, particularly in generating inferences that are both coherent and novel.Comment: AAAI 202

Structure detection in the D1 CFHTLS deep field using accurate photometric redshifts: a benchmark

We investigate structures in the D1 CFHTLS deep field in order to test the method that will be applied to generate homogeneous samples of clusters and groups of galaxies in order to constrain cosmology and detailed physics of groups and clusters. Adaptive kernel technique is applied on galaxy catalogues. This technique needs none of the usual a-priori assumptions (luminosity function, density profile, colour of galaxies) made with other methods. Its main drawback (decrease of efficiency with increasing background) is overcame by the use of narrow slices in photometric redshift space. There are two main concerns in structure detection. One is false detection and the second, the evaluation of the selection function in particular if one wants "complete" samples. We deal here with the first concern using random distributions. For the second, comparison with detailed simulations is foreseen but we use here a pragmatic approach with comparing our results to GalICS simulations to check that our detection number is not totally at odds compared to cosmological simulations. We use XMM-LSS survey and secured VVDS redshifts up to z~1 to check individual detections. We show that our detection method is basically capable to recover (in the regions in common) 100% of the C1 XMM-LSS X-ray detections in the correct redshift range plus several other candidates. Moreover when spectroscopic data are available, we confirm our detections, even those without X-ray data.Comment: 14 pages, 22 additionnal jpeg figures, accepted in A&

STAR-loc: Dataset for STereo And Range-based localization

This document contains a detailed description of the STAR-loc dataset. For a quick starting guide please refer to the associated Github repository (https://github.com/utiasASRL/starloc). The dataset consists of stereo camera data (rectified/raw images and inertial measurement unit measurements) and ultra-wideband (UWB) data (range measurements) collected on a sensor rig in a Vicon motion capture arena. The UWB anchors and visual landmarks (Apriltags) are of known position, so the dataset can be used for both localization and Simultaneous Localization and Mapping (SLAM).Comment: 15 pages, 15 figure

Integrated single- and two-photon light sheet microscopy using accelerating beams

The authors thank the UK Engineering and Physical Sciences Research Council (grant EP/J01771/X) and the European Union project FAMOS (FP7 ICT, contract no. 317744) for funding. P.P. acknowledges funding by the Estonian Research Council (grants PUTJD8 and PUT369).We demonstrate the first light sheet microscope using propagation invariant, accelerating Airy beams that operates both in single- and two-photon modes. The use of the Airy beam permits us to develop an ultra compact, high resolution light sheet system without beam scanning. In two-photon mode, an increase in the field of view over the use of a standard Gaussian beam by a factor of six is demonstrated. This implementation for light sheet microscopy opens up new possibilities across a wide range of biomedical applications, especially for the study of neuronal processes.Publisher PDFPeer reviewe

Hubble Space Telescope Imaging of the CFRS and LDSS Redshift Surveys---III. Field elliptical galaxies at 0.2 < z < 1.0

Surface photometry has been performed on a sample of 46 field elliptical galaxies. These galaxies are described well by a deVaucouleurs R^{1/4} profile. The sample was selected from the combined Canada-France and LDSS redshift surveys and spans the range 0.20 < z < 1.00. The relationship between galaxy half-light radius and luminosity evolves such that a galaxy of a given size is more luminous by Delta M_B=-0.97 \pm 0.14 mag at z=0.92 and the mean rest-frame color shifts blueward by Delta (U-V) =-0.68 \pm 0.11 at z=0.92 relative to the local cluster relations. Approximately 1/3 of these elliptical galaxies exhibit [OII] 3727 emission lines with equivalent widths > 15 angstroms indicating ongoing star formation. Estimated star-formation rates imply that \le 5% of the stellar mass in the elliptical galaxy population has been formed since z=1. We see no evidence for a decline in the space density of early-type galaxies with look-back time. The statistics and a comparison with local luminosity functions are both consistent with the view that the population of massive early-type galaxies was largely in place by z~1. This implies that merging is not required since that time to produce the present-day space density of elliptical galaxies.Comment: 21 pages plus 8 figures plus 5 tables. Accepted by Astrophysical Journa

Geometrical tests of cosmological models. III. The cosmology-evolution diagram at z=1

The rotational velocity of distant galaxies, when interpreted as a size (luminosity) indicator, may be used as a tool to select high redshift standard rods (candles) and probe world models and galaxy evolution via the classical angular diameter-redshift or Hubble diagram tests. We implement the proposed testing strategy using a sample of 30 rotators spanning the redshift range 0.2<z<1 with high resolution spectra and images obtained by the VIMOS/VLT Deep Redshift Survey (VVDS) and the Great Observatories Origins Deep Survey (GOODs). We show that by applying at the same time the angular diameter-redshift and Hubble diagrams to the same sample of objects (i.e. velocity selected galactic discs) one can derive a characteristic chart, the cosmology-evolution diagram, mapping the relation between global cosmological parameters and local structural parameters of discs such as size and luminosity. This chart allows to put constraints on cosmological parameters when general prior information about discs evolution is available. In particular, by assuming that equally rotating large discs cannot be less luminous at z=1 than at present (M(z=1) < M(0)), we find that a flat matter dominated cosmology (Omega_m=1) is excluded at a confidence level of 2sigma and an open cosmology with low mass density (Omega_m = 0.3) and no dark energy contribution is excluded at a confidence level greater than 1 sigma. Inversely, by assuming prior knowledge about the cosmological model, the cosmology-evolution diagram can be used to gain useful insights about the redshift evolution of the structural parameters of baryonic discs hosted in dark matter halos of nearly equal masses.Comment: 14 pages and 11 figures. A&A in pres

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n=4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8+/-5.9 vs 59+/-2.0 mmHg), increased cardiac output (7.26+/-1.86 vs 3.30+/-0.40 l/min) and decreased systemic vascular resistance (8.48+/-2.75 vs 16.2+/-1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636+/-95 vs 301+/-26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23+/-0.05 vs 7.45+/-0.02) and prothrombin time (36+/-2 vs 8.9+/-0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5+/-210 vs 42+/-8.14) coincided with a marked reduction in serum albumin (11.5+/-1.71 vs 25+/-1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2+/-36.5 vs 131.6+/-9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems