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This paper investigated the achievable accuracy from a low-cost RTK (Real Time Kinematic)/PPK (Post Processing Kinematic) GNSS (Global Navigation Satellite Systems) system installed on board a UAV (Unmanned Aerial Vehicle), employing three different types of GNSS Bases (Alloy, RS2 and RING) working in PPK mode. To evaluate the quality of the results, a set of seven GCPs (Ground Control Points) measured by means of the NRTK (Network Real Time Kinematic) technique was used. The outcomes show a RMSE (Root Mean Square Error) of 0.0189 m for an ALLOY Base, 0.0194 m for an RS2 Base and 0.0511 m for RING Base, respectively, on the vertical value of DEMs (Digital Elevation Models) obtained by a photogrammetric process. This indicates that, when changing the Base for the PPK, the solutions are different, but they can still be considered adequate for precision positioning with UAVs, especially when GCPs could be used with some difficulty. Therefore, the integration of a RTK/PPK GNSS module on a UAV allows the reconstruction of a highly detailed and precise DEM without using GCPs and provides the possibility to carry out surveys in inaccessible areas.

To develop a population pharmacokinetic (PK) model of tacrolimus in Chinese Han renal transplant population and establish the influence of different covariates (especially different / / genotype) on PK properties. Trough tacrolimus concentrations, clinical characteristics and genotypes were collected from 141 adult renal transplant recipients after transplantation. The population PK analysis was carried out using the nonlinear mixed-effect modeling software NONMEM version 3.4.2. Tacrolimus PK profiles exhibited high interpatient variability. A two compartment model with first-order input and elimination described the tacrolimus PK profiles in the studied population. Among the genotypes, only genotype was confirmed to have clinical significance. Our final model confirmed that plays a more significant role in tacrolimus PK and could affect the blood concentrations and CL/F (clearance rate/bioavailbility). This model is expected to help to improve individualized tacrolimus dosing.

The Google Smartphone Decimeter Challenge (GSDC) was a competition held in 2021, where data from a variety of instruments useful for determining a phone’s position (signals from GPS satellites, accelerometer readings, gyroscope readings, etc.) using Android smartphones were provided to be processed/assessed in regard to the most accurate determination of the longitude and latitude of user positions. One of the tools that can be utilized to process the GNSS measurements is RTKLIB. RTKLIB is an open-source GNSS processing software tool that can be used with the GNSS measurements, including code, carrier, and doppler measurements, to provide real-time kinematic (RTK), precise point positioning (PPP), and post-processed kinematic (PPK) solutions. In the GSDC, we focused on the PPK capabilities of RTKLIB, as the challenge only required post-processing of past data. Although PPK positioning is expected to provide sub-meter level accuracies, the lower quality of the Android measurements compared to geodetic receivers makes this performance difficult to achieve consistently. Another latent issue is that the original RTKLIB created by Tomoji Takasu is aimed at commercial GNSS receivers rather than smartphones. Therefore, the performance of the original RTKLIB for the GSDC is limited. Consequently, adjustments to both the code-base and the default settings are suggested. When implemented, these changes allowed RTKLIB processing to score 5th place, based on the performance submissions of the prior GSDC competition. Detailed information on what was changed, and the steps to replicate the final results, are presented in the paper. Moreover, the updated code-base, with all the implemented changes, is provided in the public repository. This paper outlines a procedure to optimize the use of RTKLIB for Android smartphone measurements, highlighting the changes needed given the low-quality measurements from the mobile phone platform (relative to the survey grade GNSS receiver), which can be used as a basis point for further optimization for future GSDC competitions.

The application of Unmanned Aerial Vehicles (UAVs), commonly known as drones, in geological, geomorphological, and geotechnical studies has gained significant attention due to their versatility and capability to capture high-resolution data from challenging terrains. This research uses drone-based high-resolution photogrammetry to assess the geomechanical properties and rockfall potential of several rock scarps within a wide area of 50 ha. Traditional methods for evaluating geomechanical parameters on rock scarps involve time-consuming field surveys and measurements, which can be hazardous in steep and rugged environments. By contrast, drone photogrammetry offers a safer and more efficient approach, allowing for the creation of detailed 3D models of a cliff area. These models provide valuable insights into the topography, geological structures, and potential failure mechanisms. This research processed the acquired drone imagery using advanced geospatial software to generate accurate orthophotos and digital elevation models. These outputs analysed the key factors contributing to rockfall triggering, including identifying discontinuities, joint orientations, kinematic analysis of failures, and fracturing frequency. More than 8.9 × 107 facets, representing discontinuity planes, were recognised and analysed for the kinematic failure modes, showing that direct toppling is the most abundant rockfall type, followed by planar sliding and flexural toppling. Three different fracturation grades were also identified based on the number of planar facets recognised on rock surfaces. The approach used in this research contributes to the ongoing development of fast, practical, low-cost, and non-invasive techniques for geomechanical assessment on vertical rock scarps. In particular, the results show the effectiveness of drone-based photogrammetry for rapidly collecting comprehensive geomechanical data valid to recognise the prone areas to rockfalls in vast regions.

Polyphosphates (polyP) are polymers of inorganic phosphates joined by high-energy bonds to form long chains. These chains are present in all forms of life but were once disregarded as ‘molecular fossils’. PolyP has gained attention in recent years following new links to diverse biological roles ranging from energy storage to cell signaling. PolyP research in humans and other higher eukaryotes is limited by a lack of suitable tools and awaits the identification of enzymatic players that would enable more comprehensive studies. Therefore, many of the most important insights have come from single-cell model systems. Here, we review determinants of polyP metabolism, regulation, and function in major microbial systems, including bacteria, fungi, protozoa, and algae. We highlight key similarities and differences that may aid in our understanding of how polyP impacts cell physiology at a molecular level.

The high mortality rate associated with single-use CRISPR-Cas9 in Escherichia coli limits its application. Recently, new CRISPR-based techniques for E.coli gene editing have emerged. Research aims to develop a system for rapid, marker-free, multi-site, and multi-copy genome editing in E.coli to advance synthetic biology. ATP, essential for energy in living organisms, plays a crucial role in various metabolic processes. To reduce the cost of ATP-requiring reactions, it is crucial to identify and efficiently express genes in ATP synthesis pathway. This study identified a single ppk gene (No.8) capable of completing the cyclic reaction. Using MUCICAT technology, the ppk gene (No.8) was inserted into various positions and copy numbers in the E.coli genome, resulting in different activity levels. The findings suggest that the difficulty of inserting the ppk gene (No.8) into the genome follows this order: IS186 < 8array < IS186 + 8array < IS1. A single genome insertion can mimic plasmid expression level. This study explores promoter competition and offers solutions, inspiring researchers in constructing the AMP-ATP cycle system in E.coli . Key points • The single ppk gene (No.8) can regenerate the AMP-ATP cycle, crucial for ATP-dependent reactions. • Inserting the ppk gene (No.8) into the cr5 site of the E.coli genome achieves expression levels comparable to the pET29a plasmid. • The expression level of the ppk gene (No.8) is not significantly affected by its copy number in the E.coli genome.

Currently, polymyxin B has been widely used in the treatment of multidrug-resistant Gram-negative pathogen infections. Due to the limited pharmacokinetic/pharmacodynamic data, the optimal dosage regimen for the recently proposed therapeutic target of the area under the concentration-time curve over 24 h in steady state divided by the minimum inhibitory concentration 50–100 mg⋅h/L has not yet been established. Moreover, most studies have focused on critically ill patients, yet there have been no studies in the field of renal transplantation. To optimize the dosage strategy and reduce the risk of toxicity, a population pharmacokinetics model of polymyxin B with the Phoenix NLME program was developed in our study. A total of 151 plasma samples from 50 patients were collected in the present study. Polymyxin B plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. A one-compartment model adequately described the data, and the clearance and volume of distribution were 1.18 L/h and 12.09 L, respectively. A larger creatinine clearance was associated with increased clearance of polymyxin B ( p < 0.01). Monte Carlo simulation showed that a regimen of a 75 mg loading dose with a 50 mg maintenance dose was a better option to achieve an optimal therapeutic effect (minimum inhibitory concentration ≤1 mg/L) and to reduce the incidence of side effects for patients with renal impairments. The developed model suggested that dosing adjustment should be based on renal function in renal transplant patients.

Unmanned aerial photogrammetric surveys are increasingly being used for mapping and studying natural hazards, such as rockfalls. Surveys using unmanned aerial vehicles (UAVs) can be performed in remote, hardly accessible, and dangerous areas, while the photogrammetric-derived products, with high spatial and temporal accuracy, can provide us with detailed information about phenomena under consideration. However, as photogrammetry commonly uses indirect georeferencing through bundle block adjustment (BBA) with ground control points (GCPs), data acquisition in the field is not only time-consuming and labor-intensive, but also extremely dangerous. Therefore, the main goal of this study was to investigate how accurate photogrammetric products can be produced by using BBA without GCPs and auxiliary data, namely using the coordinates X0, Y0 and Z0 of the camera perspective centers computed with PPK (Post-Processing Kinematic). To this end, orthomosaics and digital surface models (DSMs) were produced for three rockfall sites by using images acquired with a DJI Phantom 4 RTK and the two different BBA methods mentioned above (hereafter referred to as BBA_traditional and BBA_PPK). The accuracy of the products, in terms of the Root Mean Square Error (RMSE), was computed by using verification points (VPs). The accuracy of both BBA methods was also assessed. To test the differences between the georeferencing methods, two statistical test were used, namely a paired Student’s t-test, and a non-parametric Wilcoxon signed-rank. The results show that the accuracy of the BBA_PPK is inferior to that of BBA_traditional, with the total RMSE values for the three sites being 0.056, 0.066, and 0.305 m, respectively, compared to 0.019, 0.036 and 0.014 m obtained with BBA_traditional. The accuracies of the BBA methods are reflected in the accuracy of the orthomosaics, whose values for the BBA_PPK are 0.039, 0.043 and 0.157 m, respectively, against 0.029, 0.036 and 0.020 m obtained with the BBA_traditional. Concerning the DSM, those produced with the BBA_PPK method present accuracy values of 0.065, 0.072 and 0.261 m, respectively, against 0.038, 0.060 and 0.030 m obtained with the BBA_traditional. Even though that there are statistically significant differences between the georeferencing methods, one can state that the BBA_PPK presents a viable solution to map dangerous and exposed areas, such as rockfall transit and deposit areas, especially for applications at a regional level.

The absence of a reliable Global Navigation Satellite System (GNSS) signal leads to degraded position robustness in standalone receivers. To address this issue, integrating GNSS with inertial measurement units (IMUs) can improve positioning accuracy. This article analyzes the performance of tightly coupled GNSS/IMU integration, specifically the forward Kalman filter and smoothing algorithm, using both single and network GNSS stations and the post-processed kinematic (PPK) method. Additionally, the impact of simulated GNSS signal outage on exterior orientation parameters (EOPs) solutions is investigated. Results demonstrate that the smoothing algorithm enhances positioning uncertainty (RMSE) for north, east, and heading by approximately 17–43% (e.g., it improves north RMSE from 51 mm to a range of 42 mm, representing a 17% improvement). Orientation uncertainty is reduced by about 60% for roll, pitch, and heading. Moreover, the algorithm mitigates the effects of GNSS signal outage, improving position uncertainty by up to 95% and orientation uncertainty by up to 60% using the smoothing algorithm instead of the forward Kalman filter for signal outages up to 180 s.

Real-Time/Post-Processing Kinematic (RTK/PPK) technology has been widely applied in Unmanned Aerial Vehicle (UAV) photogrammetry in glaciological research. Considering that ground control points (GCPs) cannot be set on glaciers, evaluating the impacts of one-sided distribution is essential. In this study, 8571 images were captured at Sermeq Avannarleq glacier in western Greenland from 4 August 2021 to the 6th, covering approximately 85 km2, with the furthest distance being 13.22 km away from the coastline. Benefited by the meandering coastline, 11 roving stations roughly uniformly distributed on bare rock were surveyed with the RTK technique. PPK-geotagged images were processed in Agisoft Metashape Professional to derive the DSMs, utilizing eight different configurations of GCP distributions that gradually extended longitudinally (along the glacier flow direction) to the upper part of the glacier. The accuracy of DSMs was evaluated by referring to the validation points (VPs) that were not employed in the Bundle Block Adjustment (BBA). The results indicated that the RMSE values of the easting, northing, and height of the reconstruction model georeferenced by only PPK geotagging (no GCPs applied) were 0.038 m, 0.031 m, and 0.146 m, respectively. Applying four GCPs located at one side of the region but with both longitudinal and lateral distribution improved the RMSE values in easting, northing, and vertical to 0.037 m, 0.031 m, and 0.081 m, respectively, and these values were stable even when distributing four GCPs evenly or when increasing the number of GCPs to eleven. Moreover, the cross-validation with ICESat-2 and ArcticDEM performed only at an off-glacier region also suggested that vertical accuracy shows significant improvements for every configuration of GCPs compared to the reconstruction model optimized only by PPK, but such improvements were not obvious if the number of GCPs exceeded four. Moreover, no elevation ramps appeared in the UAV DSM, even for the GCP configuration with only two GCPs distributed at the terminus. Therefore, combining PPK with only a few GCPs but distributing in both directions of the surveying region can offer a viable solution for obtaining glacier DSMs at the coastline with decimeter-level accuracy.