Dual-Signal Chemical Exchange Saturation Transfer (Dusi-CEST): An Efficient Strategy for Visualizing Drug Delivery Monitoring in Living Cells.

We report a dual-signal chemical exchange saturation transfer (Dusi-CEST) strategy for drug delivery and detection in living cells. The two signals can be detected by operators in complex environments. This strategy is demonstrated on a cucurbit[6]uril (CB[6]) nanoparticle probe, as an example. The CB[6] probe is equipped with two kinds of hydrophobic cavities: one is found inside CB[6] itself, whereas the other exists inside the nanoparticle. When the probe is dispersed in aqueous solution as part of a hyperpolarized 129Xe NMR experiment, two signals appear at two different chemical shifts (100 and 200 ppm). These two resonances correspond to the NMR signals of 129Xe in the two different cavities. Upon loading with hydrophobic drugs, such as paclitaxel, for intracellular drug delivery, the two resonances undergo significant changes upon drug loading and cargo release, giving rise to a metric enabling the assessment of drug delivery success. The simultaneous change of Dusi-CEST likes a mobile phone that can receive both LTE and Wi-Fi signals, which can help reduce the occurrence of false positives and false negatives in complex biological environments and help improve the accuracy and sensitivity of single-shot detection.

Preoperative combination score of neutrophils, monocytes, and lymphocytes as a predictor for locally advanced rectal cancer.

OBJECTIVE: The aim of this study was to investigate the prognostic value of baseline peripheral blood neutrophils, monocytes, and lymphocytes on locally advanced rectal cancer (LARC) patients. METHODS: Clinicopathologic data of 317 LARC patients during July 2010 and October 2016 were retrospectively gathered. X-tile software was used to acquire the optimal cutoff values of neutrophils, monocytes, and lymphocytes. Peripheral blood immune score (PBIS) system was proposed and built based on neutrophils, monocytes, and lymphocytes. The Cox model was used to analyze the associations between clinicopathological characteristics and potential outcomes. C-index was used to assess model performance. A nomogram was constructed to predict prognosis, and a calibration plot was used to verify the accuracy of the nomogram prediction model. RESULTS: Cutoff values of neutrophils, lymphocytes, and monocytes were 4.46 (× 109/L), 1.66 (× 109/L), and 0.39 (× 109/L), respectively. PBIS was related to sex (P < 0.001), tumor length (P = 0.003), and tumor thickness (P = 0.014). Multivariate Cox regression analysis revealed that PBIS (HR = 0.707, 95% CI: 0.549-0.912, P = 0.008) was an independent predictor of DFS. High PBIS (HR = 0.697, 95% CI: 0.492-0.988, P = 0.043) and high lymphocyte count (HR = 0.511, 95%CI: 0.273-0.958, P = 0.036) were favorable factors of OS. Both C-index (0.74, 95% CI: 0.549-0.912) and the calibration plot showed good prediction ability of the nomogram for DFS. CONCLUSION: PBIS, composed of baseline peripheral blood neutrophils, monocytes, and lymphocytes, is an independent predictor of the prognosis of LARC. Combination of PBIS and ypTNM stage may be a promising marker to guide adjuvant therapy after the operation.

Innate lymphoid cells exhibited IL-17-expressing phenotype in active tuberculosis disease.

BACKGROUND: Innate lymphoid cells (ILCs), as an important group of innate immunity, could respond rapidly to Mycobacterium tuberculosis (Mtb) infection. In this research, we studied the phenotypic changes of circulatory ILCs in active tuberculosis (TB) disease. METHODS: We recruited 40 patients with active Mtb infection (TB group) and 41 healthy subjects (NC group), and collected their clinical information and peripheral blood. Circulating ILCs, ILC subsets, dendritic cells (DCs), macrophages, and the production of cytokines in ILCs were tested by flow cytometry (FCM). Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma IL-23. RESULTS: Compared with healthy control, total ILCs (0.73% vs. 0.42%, P = 0.0019), ILC1 (0.55% vs. 0.31%, P = 0.0024) and CD117+ ILC2 (0.02% vs. 0.01%, P = 0.0267) were upregulated in TB group. The total IL-17+ lymphocytes were elevated (3.83% vs. 1.76%, P = 0.0006) while the IL-22+ lymphocytes remained unchanged. Within ILC subsets, ILC3, CD117+ ILC2 and ILC1 in TB group all expressed increased IL-17 (15.15% vs. 4.55%, 19.01% vs. 4.57%, 8.79% vs. 3.87%, P < 0.0001) but similar IL-22 comparing with healthy control. TB group had more plasma IL-23 than NC group (7.551 vs. 5.564 pg/mL, P = 0.0557). Plasma IL-23 in TB group was positively correlated to IL-17+ ILC3 (r = 0.4435, P = 0.0141), IL-17+CD117+ ILC2 (r = 0.5385, P = 0.0021) and IL-17+ ILC1(r = 0.3719, P = 0.0430). TB group also had elevated DCs (9.35% vs. 6.49%, P < 0.0001) while macrophages remained unchanged. Within TB group, higher proportion of IL-17+ ILCs was related to severer inflammatory status and poorer clinical condition. CONCLUSIONS: In active TB disease, circulatory ILCs were upregulated and exhibited IL-17-expressing phenotype. This may expand the understanding of immune reaction to Mtb infection.

Modulation of autophagy in traumatic brain injury.

Traumatic brain injury (TBI) is defined as a traumatically induced structural injury or physiological disruption of brain function as a result of external forces, leading to adult disability and death. A growing body of evidence reveals that alterations in autophagy-related proteins exist extensively in both experimentally and clinically after TBI. Of note, the autophagy pathway plays an essential role in pathophysiological processes, such as oxidative stress, inflammatory response, and apoptosis, thus contributing to neurological properties of TBI. With this in mind, this review summarizes a comprehensive overview on the beneficial and detrimental effects of autophagy in pathophysiological conditions and how these activities are linked to the pathogenesis of TBI. Moreover, the relationship between oxidative stress, inflammation, apoptosis, and autophagy occur TBI. Ultimately, multiple compounds and various drugs targeting the autophagy pathway are well described in TBI. Therefore, autophagy flux represents a potential clinical therapeutic value for the treatment of TBI and its complications.

Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and ß-cell function.

Osteocalcin (OCN) is a bone-derived hormone involved in the regulation of glucose metabolism. In serum, OCN exists in carboxylated and uncarboxylated forms (ucOCN), and studies in rodents suggest that ucOCN is the bioactive form of this hormone. Whether this is also the case in humans is unclear, because a reliable assay to measure ucOCN is not available. Here, we established and validated a new immunoassay (ELISA) measuring human ucOCN and used it to determine the level of bioactive OCN in two cohorts of overweight or obese subjects, with or without type 2 diabetes (T2D). The ELISA could specifically detect ucOCN concentrations ranging from 0.037 to 1.8 ng/mL. In a first cohort of overweight or obese postmenopausal women without diabetes (n = 132), ucOCN correlated negatively with fasting glucose (r = -0.18, P = 0.042) and insulin resistance assessed by the homeostatic model assessment of insulin resistance (r = -0.18, P = 0.038) and positively with insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp (r = 0.18, P = 0.043) or insulin sensitivity index derived from an oral glucose tolerance test (r = 0.26, P = 0.003). In a second cohort of subjects with severe obesity (n = 16), ucOCN was found to be lower in subjects with T2D compared with those without T2D (2.76 ± 0.38 versus 4.52 ± 0.06 ng/mL, P = 0.009) and to negatively correlate with fasting glucose (r = -0.50, P = 0.046) and glycated hemoglobin (r = -0.57, P = 0.021). Moreover, the subjects with ucOCN levels below 3 ng/mL had a reduced insulin secretion rate during a hyperglycemic clamp (P = 0.03). In conclusion, ucOCN measured with this novel and specific assay is inversely associated with insulin resistance and ß-cell dysfunction in humans.

Extracting Common Mode Errors of Regional GNSS Position Time Series in the Presence of Missing Data by Variational Bayesian Principal Component Analysis.

Removal of the common mode error (CME) is very important for the investigation of global navigation satellite systems' (GNSS) error and the estimation of an accurate GNSS velocity field for geodynamic applications. The commonly used spatiotemporal filtering methods normally process the evenly spaced time series without missing data. In this article, we present the variational Bayesian principal component analysis (VBPCA) to estimate and extract CME from the incomplete GNSS position time series. The VBPCA method can naturally handle missing data in the Bayesian framework and utilizes the variational expectation-maximization iterative algorithm to search each principal subspace. Moreover, it could automatically select the optimal number of principal components for data reconstruction and avoid the overfitting problem. To evaluate the performance of the VBPCA algorithm for extracting CME, 44 continuous GNSS stations located in Southern California were selected. Compared to previous approaches, VBPCA could achieve better performance with lower CME relative errors when more missing data exists. Since the first principal component (PC) extracted by VBPCA is remarkably larger than the other components, and its corresponding spatial response presents nearly uniform distribution, we only use the first PC and its eigenvector to reconstruct the CME for each station. After filtering out CME, the interstation correlation coefficients are significantly reduced from 0.43, 0.46, and 0.38 to 0.11, 0.10, and 0.08, for the north, east, and up (NEU) components, respectively. The root mean square (RMS) values of the residual time series and the colored noise amplitudes for the NEU components are also greatly suppressed, with average reductions of 27.11%, 28.15%, and 23.28% for the former, and 49.90%, 54.56%, and 49.75% for the latter. Moreover, the velocity estimates are more reliable and precise after removing CME, with average uncertainty reductions of 51.95%, 57.31%, and 49.92% for the NEU components, respectively. All these results indicate that the VBPCA method is an alternative and efficient way to extract CME from regional GNSS position time series in the presence of missing data. Further work is still required to consider the effect of formal errors on the CME extraction during the VBPCA implementation.

Wnt/ß-catenin signaling cascade: A promising target for glioma therapy.

Glioma is one of the most treatment-refractory intracranial tumors, and the aberrant expressed Wnt/ß-catenin pathway is closely associated with glioma malignancy. In this regard, Wnt/ß-catenin signaling has been reported to play an essential role in cellular proliferation, migration, invasion, and angiogenesis, therefore contributing to glioma progression. However, the underlying mechanisms of Wnt/ß-catenin signaling involvement in gliomagenesis remain unknown. Here, we present an overview of the Wnt components and then go on to summarize the current knowledge describing the multitude of roles of Wnt/ß-catenin in glioma, which are mediated by transcription factors, microRNAs, long noncoding RNAs, and so on. In the latter portion of the review, we elaborate the increasing apparent crosstalk of Wnt/ß-catenin pathway with PI3K/AKT signaling involved in these processes. Ultimately, compounds targeting the Wnt/ß-catenin are described in glioma. As better understanding of the regulatory mechanisms to glioma malignancies increases, Wnt/ß-catenin cascade may represent an area of developmental glioma therapeutics focus.

Improving the GRACE Kinematic Precise Orbit Determination Through Modified Clock Estimating.

Utilizing global positioning system (GPS) to determine the precise kinematic orbits for the twin satellites of the Gravity Recovery and Climate Experiment (GRACE) plays a very important role in the earth's gravitational and other scientific fields. However, the orbit quality is highly depended on the geometry of observed GPS satellites. In this study, we propose a kinematic orbit determination method for improving the GRACE orbit quality especially when the geometry of observed GPS satellites is weak, where an appropriate random walk clock constraint between adjacent epochs is recommended according to the stability of on-board GPS receiver clocks. GRACE data over one month were adopted in the experimental validation. Results show that the proposed method could improve the root mean square (RMS) by 20-40% in radial component and 5-20% in along and cross components. For those epochs with position dilution of precision (PDOP) larger than 4, the orbits were improved by 50-70% in radial component and 17-50% in along and cross components. Meanwhile, the Allan deviation of clock estimates in the proposed method was much closer to the reported Allan deviation of GRACE on-board oscillator. All the results confirmed the improvement of the proposed method.

Analysis of BDS Fractional Cycle Biases and PPP Ambiguity Resolution.

It is difficult to enable traditional precise point positioning (PPP) with ambiguity resolution (AR) due to fractional cycle biases (FCBs), which limit the accuracy and reliability of positioning results. The BeiDou Navigation Satellite System (BDS) has been providing continuous positioning, navigation, and timing (PNT) services in the global region since the end of 2018. The BDS constellation includes geostationary earth orbit (GEO), inclined geostationary orbit (IGSO), and medium earth orbit (MEO) satellites. However, its hybrid constellation structure and the satellite-side multipath effect have hindered the BDS PPP AR for two main reasons: (1) some receivers have half-cycle biases between GEO and non-GEO satellites, which result in the inconsistency of hardware delays for each satellite type; (2) the correction model for elevation-dependent satellite-side multipath effect is only applicable to IGSO and MEO, while in the case of GEO the effect cannot be effectively weakened or eliminated. To rectify these problems, a suitable strategy is proposed for estimating BDS FCBs, whereby the GEO FCBs and non-GEO FCBs are estimated independently. Results show that the FCBs estimated by the new strategy for GEO and non-GEO are more stable compared to the traditional strategy. The GEO wide-lane (WL) FCBs fluctuate less than 0.3 cycle in one month, except for C05, while the variation of non-GEO WL FCBs is about 0.1 cycle. In addition, compared to the traditional strategy, the fractions of GEO WL ambiguities after the removal of FCBs estimated by the new strategy can be improved noticeably from 53.5% to 78.5%, and from 71.8% to 92.3% for <0.15 cycle and <0.25 cycle respectively, which could be comparable with non-GEO. Simultaneously, the improvement of GEO narrow-lane (NL) ambiguities is from 28.9% to 40.2%, and from 40.4% to 53.3% for <0.10 cycle and <0.15 cycle respectively, are less noticeable. This is mainly due to the low precision IGS products for GEO. After PPP AR, the mean convergence time is shorted from 56.0 min to 43.6 min, and from 71.6 min to 62.7 min for static PPP and kinematic PPP, respectively.

The Alzheimer's disease-protective CD33 splice variant mediates adaptive loss of function via diversion to an intracellular pool.

The immunomodulatory receptor Siglec-3/CD33 influences risk for late-onset Alzheimer's disease (LOAD), an apparently human-specific post-reproductive disease. CD33 generates two splice variants: a full-length CD33M transcript produced primarily by the "LOAD-risk" allele and a shorter CD33m isoform lacking the sialic acid-binding domain produced primarily from the "LOAD-protective" allele. An SNP that modulates CD33 splicing to favor CD33m is associated with enhanced microglial activity. Individuals expressing more protective isoform accumulate less brain ß-amyloid and have a lower LOAD risk. How the CD33m isoform increases ß-amyloid clearance remains unknown. We report that the protection by the CD33m isoform may not be conferred by what it does but, rather, from what it cannot do. Analysis of blood neutrophils and monocytes and a microglial cell line revealed that unlike CD33M, the CD33m isoform does not localize to cell surfaces; instead, it accumulates in peroxisomes. Cell stimulation and activation did not mobilize CD33m to the surface. Thus, the CD33m isoform may neither interact directly with amyloid plaques nor engage in cell-surface signaling. Rather, production and localization of CD33m in peroxisomes is a way of diminishing the amount of CD33M and enhancing ß-amyloid clearance. We confirmed intracellular localization by generating a CD33m-specific monoclonal antibody. Of note, CD33 is the only Siglec with a peroxisome-targeting sequence, and this motif emerged by convergent evolution in toothed whales, the only other mammals with a prolonged post-reproductive lifespan. The CD33 allele that protects post-reproductive individuals from LOAD may have evolved by adaptive loss-of-function, an example of the less-is-more hypothesis.

Studies on the Detection, Expression, Glycosylation, Dimerization, and Ligand Binding Properties of Mouse Siglec-E.

CD33-related Siglecs are a family of proteins widely expressed on innate immune cells. Binding of sialylated glycans or other ligands triggers signals that inhibit or activate inflammation. Immunomodulation by Siglecs has been extensively studied, but relationships between structure and functions are poorly explored. Here we present new data relating to the structure and function of Siglec-E, the major CD33-related Siglec expressed on mouse neutrophils, monocytes, macrophages, and dendritic cells. We generated nine new rat monoclonal antibodies specific to mouse Siglec-E, with no cross-reactivity to Siglec-F. Although all antibodies detected Siglec-E on transfected human HEK-293T cells, only two reacted with mouse bone marrow neutrophils by flow cytometry and on spleen sections by immunohistochemistry. Moreover, whereas all antibodies recognized Siglec-E-Fc on immunoblots, binding was dependent on intact disulfide bonds and N-glycans, and only two antibodies recognized native Siglec-E within spleen lysates. Thus, we further investigated the impact of Siglec-E homodimerization. Homology-based structural modeling predicted a cysteine residue (Cys-298) in position to form a disulfide bridge between two Siglec-E polypeptides. Mutagenesis of Cys-298 confirmed its role in dimerization. In keeping with the high level of 9-O-acetylation found in mice, sialoglycan array studies indicate that this modification has complex effects on recognition by Siglec-E, in relationship to the underlying structures. However, we found no differences in phosphorylation or SHP-1 recruitment between dimeric and monomeric Siglec-E expressed on HEK293A cells. Phylogenomic analyses predicted that only some human and mouse Siglecs form disulfide-linked dimers. Notably, Siglec-9, the functionally equivalent human paralog of Siglec-E, occurs as a monomer.

Comprehensive Bioinformatic Analysis Genes Associated to the Prognosis of Liposarcoma.

BACKGROUND Liposarcoma is the most common type of soft tissue sarcoma, but its molecular mechanism is poorly defined. This study aimed to identify genes crucial to the pathogenesis of liposarcoma and to explore their functions, related pathways, and prognostic value. MATERIAL AND METHODS Differentially expressed genes (DEGs) in the GSE59568 dataset were screened. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to investigate the DEGs at the functional level. Protein-protein interaction (PPI) networks and module analysis were applied to identify hub genes from among the DEGs. The GSE30929 dataset was used to validate the relationship between hub genes and the distant recurrence-free survival (DRFS) of liposarcoma patients using Cox model analysis. RESULTS A total of 1111 DEGs were identified. GO and KEGG pathway analysis indicated that the DEGs were mainly associated with lipopolysaccharides and pathways in cancer. The PPI network and module analysis identified 10 hub genes from the DEG network. The Cox model identified 3 genes (NIP7, RPL10L, and MCM2) significantly associated with DRFS. The risk score calculated by the Cox model of the NIP7-RPL10L-MCM2 signature could largely predict the 1-, 3-, and 5-year DRFS of liposarcoma patients, and the prognostic value was even higher for subtypes of liposarcoma. CONCLUSIONS This study identified genes that might play critical roles in liposarcoma pathogenesis as well as a 3-gene-based signature that could be used as a candidate prognostic biomarker for patients with liposarcoma.

Hyperpolarized 129 Xe Magnetic Resonance Imaging Sensor for H2 S.

A new magnetic resonance imaging (MRI) molecular sensor for hydrogen sulfide detection and imaging using the nuclear spin resonance of hyperpolarized 129 Xe is developed. The designed MRI sensor employs cryptophane for NMR sensing, together with an azide group serving as a reaction site. It demonstrates a "proof-of-concept" that a fluorescent H2 S probe can be linked to a xenon-binding cryptophane and thereby converted into an MRI probe, which could provide a very generalizable template.

Combining CHAMP and Swarm Satellite Data to Invert the Lithospheric Magnetic Field in the Tibetan Plateau.

CHAMP and Swarm satellite magnetic data are combined to establish the lithospheric magnetic field over the Tibetan Plateau at satellite altitude by using zonal revised spherical cap harmonic analysis (R-SCHA). These data are integrated with geological structures data to analyze the relationship between magnetic anomaly signals and large-scale geological tectonic over the Tibetan Plateau and to explore the active tectonic region based on the angle of the magnetic anomaly. Results show that the model fitting error is small for a layer 250-500 km high, and the RMSE of the horizontal and radial geomagnetic components is better than 0.3 nT. The proposed model can accurately describe medium- to long-scale lithospheric magnetic anomalies. Analysis indicates that a negative magnetic anomaly in the Tibetan Plateau significantly differs with a positive magnetic anomaly in the surrounding area, and the boundary of the positive and negative regions is generally consistent with the geological tectonic boundary in the plateau region. Significant differences exist between the basement structures of the hinterland of the plateau and the surrounding area. The magnetic anomaly in the Central and Western Tibetan Plateau shows an east-west trend, which is identical to the direction of the geological structures. The magnetic anomaly in the eastern part is arc-shaped and extends along the northeast direction. Its direction is significantly different from the trend of the geological structures. The strongest negative anomaly is located in the Himalaya block, with a central strength of up to -9 nT at a height of 300 km. The presence of a strong negative anomaly implies that the Curie isotherm in this area is relatively shallow and deep geological tectonic activity may exist.

Tissue Characterization with Quantitative High-Resolution Magic Angle Spinning Chemical Exchange Saturation Transfer Z-Spectroscopy.

Chemical exchange saturation transfer (CEST) provides sensitive magnetic resonance (MR) contrast for probing dilute compounds via exchangeable protons, serving as an emerging molecular imaging methodology. CEST Z-spectrum is often acquired by sweeping radiofrequency saturation around bulk water resonance, offset by offset, to detect CEST effects at characteristic chemical shift offsets, which requires prolonged acquisition time. Herein, combining high-resolution magic angle spinning (HRMAS) with concurrent application of gradient and rf saturation to achieve fast Z-spectral acquisition, we demonstrated the feasibility of fast quantitative HRMAS CEST Z-spectroscopy. The concept was validated with phantoms, which showed excellent agreement with results obtained from conventional HRMAS MR spectroscopy (MRS). We further utilized the HRMAS Z-spectroscopy for fast ex vivo quantification of ischemic injury with rodent brain tissues after ischemic stroke. This method allows rapid and quantitative CEST characterization of biological tissues and shows potential for a host of biomedical applications.

Biothiol Xenon MRI Sensor Based on Thiol-Addition Reaction.

Biothiols such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) play an important role in regulating the vital functions of living organisms. Knowledge of their biodistribution in real-time could help diagnose a variety of conditions. However, existing methods of biothiol detection are invasive and require assays. Herein we report a molecular biosensor for biothiol detection using the nuclear spin resonance of (129)Xe. The (129)Xe biosensor consists of a cryptophane cage encapsulating a xenon atom and an acrylate group. The latter serves as a reactive site to covalently bond biothiols through a thiol-addition reaction. The biosensor enables discrimination of Cys from Hcy and GSH through the chemical shift and average reaction rate. This biosensor can be detected at a concentration of 10 µM in a single scan and it has been applied to detect biothiols in bovine serum solution. Our results indicate that this biosensor is a promising tool for the real-time imaging of biothiol distributions.

A Molecular Imaging Approach to Mercury Sensing Based on Hyperpolarized (129)Xe Molecular Clamp Probe.

Mercury pollution, in the form of mercury ions (Hg(2+)), is a major health and environmental hazard. Commonly used sensors are invasive and limited to point measurements. Fluorescence-based sensors do not provide depth resolution needed to image spatial distributions. Herein we report a novel sensor capable of yielding spatial distributions by MRI using hyperpolarized (129)Xe. A molecular clamp probe was developed consisting of dipyrrolylquinoxaline (DPQ) derivatives and twocryptophane-A cages. The DPQ derivatives act as cation receptors whereas cryptophane-A acts as a suitable host molecule for xenon. When the DPQ moiety interacts with mercury ions, the molecular clamp closes on the ion. Due to overlap of the electron clouds of the two cryptophane-A cages, the shielding effect on the encapsulated Xe becomes important. This leads to an upfield change of the chemical shift of the encapsulated Xe. This sensor exhibits good selectivity and sensitivity toward the mercury ion. This mercury-activated hyperpolarized (129)Xe-based chemosensor is a new concept method for monitoring Hg(2+) ion distributions by MRI.

Estimates of minor ocean tide loading displacement and its impact on continuous GPS coordinate time series.

The site displacement due to ocean tidal loading is regarded as one of the largest uncertainties in precise geodetic positioning measurements, among which the effect of minor ocean tides (MOT), except for the 11 main tidal constituents, are sometimes neglected in routine precise global positioning system (GPS) data processing. We find that MOT can cause large vertical loading displacements with peak-to-peak variations reaching more than 8 mm at coastal/island stations. The impact of MOT on the 24-hour GPS solution is slightly larger than the magnitude of MOT loading itself, with peak-to-peak displacement variation at about 10 mm for the horizontal and 30 mm for the vertical components. We also find that the vertical velocity of all the selected stations in the Southwest Pacific was reduced by more than 10% after considering the MOT effect, while stations with weighted root mean square reduced data account for 62%, 59%, and 36% for the up, east, and north components respectively, in particular for most coastal/island stations. Furthermore, MOT correction could significantly reduce the annual signal of the global stacked east component, the near fortnightly and the long-term periodic signals in the up component. The power of some anomalous harmonics of 1.04 cycle per year is also decreased to some extent. These results further proved the benefits of MOT correction in precise GPS data processing.

Efficient high-rate satellite clock estimation for PPP ambiguity resolution using carrier-ranges.

In order to catch up the short-term clock variation of GNSS satellites, clock corrections must be estimated and updated at a high-rate for Precise Point Positioning (PPP). This estimation is already very time-consuming for the GPS constellation only as a great number of ambiguities need to be simultaneously estimated. However, on the one hand better estimates are expected by including more stations, and on the other hand satellites from different GNSS systems must be processed integratively for a reliable multi-GNSS positioning service. To alleviate the heavy computational burden, epoch-differenced observations are always employed where ambiguities are eliminated. As the epoch-differenced method can only derive temporal clock changes which have to be aligned to the absolute clocks but always in a rather complicated way, in this paper, an efficient method for high-rate clock estimation is proposed using the concept of "carrier-range" realized by means of PPP with integer ambiguity resolution. Processing procedures for both post- and real-time processing are developed, respectively. The experimental validation shows that the computation time could be reduced to about one sixth of that of the existing methods for post-processing and less than 1 s for processing a single epoch of a network with about 200 stations in real-time mode after all ambiguities are fixed. This confirms that the proposed processing strategy will enable the high-rate clock estimation for future multi-GNSS networks in post-processing and possibly also in real-time mode.