GNSS Reliability Testing in Signal-Degraded Scenario

Multiconstellation satellite navigation is critical in signal-degraded environments where signals are strongly corrupted. In this case, the use of a single GNSS system does not guarantee an accurate and continuous positioning. A possible approach to solve this problem is the use of multiconstellation receivers that provide additional measurements and allows robust reliability testing; in this work, a GPS/GLONASS combination is considered. In urban scenario, a modification of the classical RAIM technique is necessary taking into account frequent multiple blunders. The FDE schemes analysed are the "Observation Subset Testing," "Forward-Backward Method," and "Danish Method"; they are obtained by combining different basic statistical tests. The considered FDE methods are modified to optimize their behaviour in urban scenario. Specifically a preliminary check is implemented to screen out bad geometries. Moreover, a large blunder could cause multiple test failures; hence, a separability index is implemented to avoid the incorrect exclusion of blunder-free measurements. Testing the RAIM algorithms of GPS/GLONASS combination to verify the benefits relative to GPS only case is a main target of this work too. The performance of these methods is compared in terms of RMS and maximum error for the horizontal and vertical components of position and velocity

Performance Assessment of PPP Surveys with Open Source Software Using the GNSS GPS\u2013GLONASS\u2013Galileo Constellations

In this work, the performance of the multi-GNSS (Global Navigation Satellite System) Precise Point Positioning (PPP) technique, in static mode, is analyzed. Specifically, GPS (Global Positioning System), GLONASS, and Galileo systems are considered, and quantifying the Galileo contribution is one of the main objectives. The open source software RTKLib is adopted to process the data, with precise satellite orbits and clocks from CNES (Centre National d\u2019Etudes Spatiales) and CLS (Collecte Localisation Satellites) analysis centers for International GNSS Service (IGS). The Iono-free model is used to correct ionospheric errors, the GOT-4.7 model is used to correct tidal effects, and Differential Code Biases (DCB) are taken from the Deutsche Forschungsanstalt f\ufcr Luftund Raumfahrt (DLR) center. Two different tropospheric models are tested: Saastamoinen and Estimate ZTD (Zenith Troposhperic Delay). For the proposed study, a dataset of 31 days from a permanent GNSS station, placed in Palermo (Italy), and a dataset of 10 days from a static geodetic receiver, placed nearby the station, have been collected and processed by the most used open source software in the geomatic community. The considered GNSS configurations are seven: GPS only, GLONASS only, Galileo only, GPS+GLONASS, GPS+Galileo, GLONASS+Galileo, and GPS+GLONASS+Galileo. The results show significant performance improvement of the GNSS combinations with respect to single GNSS cases

Performance assessment of PPP surveys with open source software using the GNSS GPS-GLONASS-Galileo constellations

In this work, the performance of the multi-GNSS (Global Navigation Satellite System) Precise Point Positioning (PPP) technique, in static mode, is analyzed. Specifically, GPS (Global Positioning System), GLONASS, and Galileo systems are considered, and quantifying the Galileo contribution is one of the main objectives. The open source software RTKLib is adopted to process the data, with precise satellite orbits and clocks from CNES (Centre National d'Etudes Spatiales) and CLS (Collecte Localisation Satellites) analysis centers for International GNSS Service (IGS). The Iono-free model is used to correct ionospheric errors, the GOT-4.7 model is used to correct tidal effects, and Differential Code Biases (DCB) are taken from the Deutsche Forschungsanstalt für Luftund Raumfahrt (DLR) center. Two different tropospheric models are tested: Saastamoinen and Estimate ZTD (Zenith Troposhperic Delay). For the proposed study, a dataset of 31 days from a permanent GNSS station, placed in Palermo (Italy), and a dataset of 10 days from a static geodetic receiver, placed nearby the station, have been collected and processed by the most used open source software in the geomatic community. The considered GNSS configurations are seven: GPS only, GLONASS only, Galileo only, GPS+GLONASS, GPS+Galileo, GLONASS+Galileo, and GPS+GLONASS+Galileo. The results show significant performance improvement of the GNSS combinations with respect to single GNSS cases

A Kalman filter single point positioning for maritime applications using a smartphone

Different positioning techniques have been largely adopted for maritime applications that require high accuracy kinematic positioning. The main objective of the paper is the performance assessment of a Single Point Positioning algorithm (SPP), with a Kalman filter (KF) estimator, adapted for maritime applications. The KF has been chosen as estimation technique due to the ability to consider both the state vector dynamic and the measurements. Particularly, in order to compute an accurate vertical component of the position, suitable for maritime applications, the KF settings have been modified by tuning the covariance matrix of the process noise. The algorithm is developed in Matlab environment and tested using multi-GNSS single-frequency raw data, collected by a smartphone located on board a moving ship. The algorithm performance evaluation is carried out in position domain and the results show an enhancement of meter order on vertical component compared to the classical SPP based on Least Square estimation technique. In addition, different GNSSs configurations are considered to verify the benefits of their integration in terms of accuracy, solution availability and geometry

Identification of Cdk8 and Cdkn2d as New Prame-Target Genes in 2C-like Embryonic Stem Cells

Embryonic stem cells (ESCs) present a characteristic pluripotency heterogeneity correspondent to specific metastates. We recently demonstrated that retinoic acid (RA) induces an increase in a specific 2C-like metastate marked by target genes specific to the two-cell embryo stage in preimplantation. Prame (Preferentially expressed antigen in melanoma) is one of the principal actors of the pluripotency stage with a specific role in RA responsiveness. Additionally, PRAME is overexpressed in a variety of cancers, but its molecular functions are poorly understood. To further investigate Prame’s downstream targets, we used a chromatin immunoprecipitation sequencing (ChIP-seq) assay in RA-enriched 2C-like metastates and identified two specific target genes, Cdk8 and Cdkn2d, bound by Prame. These two targets, involved in cancer dedifferentiation and pluripotency, have been further validated in RA-resistant ESCs. Here, we observed for the first time that Prame controls the Cdk8 and Cdkn2d genes in ESCs after RA treatment, shedding light on the regulatory network behind the establishment of naïve pluripotency

Sea state monitoring by ship motion measurements onboard a research ship in the antarctic waters

A parametric wave spectrum resembling procedure is applied to detect the sea state parameters, namely the wave peak period and significant wave height, based on the measurement and analysis of the heave and pitch motions of a vessel in a seaway, recorded by a smartphone located onboard the ship. The measurement system makes it possible to determine the heave and pitch acceleration spectra of the reference ship in the encounter frequency domain and, subsequently, the absolute sea spectra once the ship motion transfer functions are provided. The measurements have been carried out onboard the research ship “Laura Bassi”, during the oceanographic campaign in the Antarctic Ocean carried out in January and February 2020. The resembled sea spectra are compared with the weather forecast data, provided by the global-WAM (GWAM) model, in order to validate the sea spectrum resembling procedure

Targeted DNA methylation by homology-directed repair in mammalian cells. Transcription reshapes methylation on the repaired gene.

We report that homology-directed repair of a DNA double-strand break within a single copy Green Fluorescent Protein (GFP) gene in HeLa cells alters the methylation pattern at the site of recombination. DNA methyl transferase (DNMT)1, DNMT3a and two proteins that regulate methylation, Np95 and GADD45A, are recruited to the site of repair and are responsible for selective methylation of the promoter-distal segment of the repaired DNA. The initial methylation pattern of the locus is modified in a transcription-dependent fashion during the 15\u201320 days following repair, at which time no further changes in the methylation pattern occur. The variation in DNA modification generates stable clones with wide ranges of GFP expression. Collectively, our data indicate that somatic DNA methylation follows homologous repair and is subjected to remodeling by local transcription in a discrete time window during and after the damage. We propose that DNA methylation of repaired genes represents a DNA damage code and is source of variation of gene expression

Dysregulation of principal cell miRNAs facilitates epigenetic regulation of AQP2 and results in nephrogenic diabetes insipidus

Background MicroRNAs (miRNAs), formed by cleavage of pre-microRNA by the endoribonuclease Dicer, are critical modulators of cell function by post-transcriptionally regulating gene expression. Methods Selective ablation of Dicer in AQP2-expressing cells (DicerAQP2Cre1 mice) was used to investigate the role of miRNAs in the kidney collecting duct of mice. Results The mice had severe polyuria and nephrogenic diabetes insipidus, potentially due to greatly reduced AQP2 and AQP4 levels. Although epithelial sodium channel levels were decreased in cortex and increased in inner medulla, amiloride-sensitive sodium reabsorption was equivalent in DicerAQP2Cre1 mice and controls. Small-RNA sequencing and proteomic analysis revealed 31 and 178 significantly regulated miRNAs and proteins, respectively. Integrated bioinformatic analysis of the miRNAome and proteome suggested alterations in the epigenetic machinery and various transcription factors regulating AQP2 expression in DicerAQP2Cre1 mice. The expression profile and function of three miRNAs (miR-7688-5p, miR-8114, and miR-409-3p) whose predicted targets were involved in epigenetic control (Phf2, Kdm5c, and Kdm4a) or transcriptional regulation (GATA3, GATA2, and ELF3) of AQP2 were validated. Luciferase assays could not demonstrate direct interaction of AQP2 or the three potential transcription factors with miR-7688-5p, miR-8114, and miR-409-3p. However, transfection of respective miRNA mimics reduced AQP2 expression. Chromatin immunoprecipitation assays demonstrated decreased Phf2 and significantly increased Kdm5c interactions at the Aqp2 gene promoter in DicerAQP2Cre1 mice, resulting in decreased RNA Pol II association. Conclusions Novel evidence indicates miRNA-mediated epigenetic regulation of AQP2 expression

The antimalarial efficacy and mechanism of resistance of the novel chemotype DDD01034957.

New antimalarial therapeutics are needed to ensure that malaria cases continue to be driven down, as both emerging parasite resistance to frontline chemotherapies and mosquito resistance to current insecticides threaten control programmes. Plasmodium, the apicomplexan parasite responsible for malaria, causes disease pathology through repeated cycles of invasion and replication within host erythrocytes (the asexual cycle). Antimalarial drugs primarily target this cycle, seeking to reduce parasite burden within the host as fast as possible and to supress recrudescence for as long as possible. Intense phenotypic drug screening efforts have identified a number of promising new antimalarial molecules. Particularly important is the identification of compounds with new modes of action within the parasite to combat existing drug resistance and suitable for formulation of efficacious combination therapies. Here we detail the antimalarial properties of DDD01034957-a novel antimalarial molecule which is fast-acting and potent against drug resistant strains in vitro, shows activity in vivo, and possesses a resistance mechanism linked to the membrane transporter PfABCI3. These data support further medicinal chemistry lead-optimization of DDD01034957 as a novel antimalarial chemical class and provide new insights to further reduce in vivo metabolic clearance