Search

This paper discusses strategies to improve the Gravity Recovery And Climate Experiment (GRACE) monthly solutions computed at the Astronomical Institute of the University of Bern (AIUB) which are contributing to the Horizon 2020 project G3P – Global Gravity-based Groundwater Product. To improve the AIUB-GRACE gravity field solutions, we updated the use of the Level-1B observations, adapted the background models, and improved the processing strategies in terms of instrument screening and parameterization. We used the Release 3 K-band product (KBR) and star camera data (L1B RL03), and we adopted Release 6 of the Atmospheric and Ocean De-aliasing (AOD1B RL06) product. For the accelerometer parameterization, we used arc-wise full scale factor matrix and arc-wise third-order polynomial biases. The new accelerometer parameterization is effective in reducing noise over the oceans in gravity field solutions, especially for the late years of the GRACE mission when the thermal control was switched off. In this paper, we show that the outliers in the KBR antenna offset correction (AOC) are projected into the range rate residuals; therefore, we used the KBR AOC as the main source for outlier detection and eliminated the AOC above a threshold for all data before the gravity field processing. The full time series of GRACE AIUB-G3P gravity field solutions (Darbeheshti et al., 2023b) is available at https://doi.org/10.5880/ICGEM.2023.001.

In the framework of the COmbination Service for Time-variable Gravity fields (COST-G) gravity field solutions from different analysis centres are combined to provide a consolidated solution of improved quality and robustness to the user. As in many other satellite-related sciences, the correct application of background models plays a crucial role in gravity field determination. Therefore, we publish a set of data of various commonly used forces in orbit and gravity field modelling (Earth's gravity field, tides etc.) evaluated along a one day orbit arc of GRACE, together with auxiliary data to enable easy comparisons. The benchmark data is compiled with the GROOPS software by the Institute of Geodesy (IfG) at Graz University of Technology. It is intended to be used as a reference data set and provides the opportunity to test the implementation of these models at various institutions involved in orbit and gravity field determination from satellite tracking data. In view of the COST-G GRACE and GRACE Follow-On gravity field combinations, we document the outcome of the comparison of the background force models for the Bernese GNSS software from AIUB (Astronomical Institute, University of Bern), the EPOS software of the German Research Centre for Geosciences (GFZ), the GINS software, developed and maintained by the Groupe de Recherche de Géodésie Spatiale (GRGS), the GRACE-SIGMA software of the Leibniz University of Hannover (LUH) and the GRASP software also developed at LUH. We consider differences in the force modelling for GRACE (-FO) which are one order of magnitude smaller than the accelerometer noise of about 10−10 m s−2 to be negligible and formulate this as a benchmark for new analysis centres, which are interested to contribute to the COST-G initiative.

Gravity field models may be derived from kinematic orbit positions of Low Earth Orbiting satellites equipped with onboard GPS (Global Positioning System) receivers. An accurate description of the stochastic behaviour of the kinematic positions plays a key role to calculate high quality gravity field solutions. In the Celestial Mechanics Approach (CMA) kinematic positions are used as pseudo-observations to estimate orbit parameters and gravity field coefficients simultaneously. So far, a simplified stochastic model based on epoch-wise covariance information, which may be efficiently derived in the kinematic point positioning process, has been applied. We extend this model by using the fully populated covariance matrix, covering correlations over 50 min. As white noise is generally assumed for the original GPS carrier phase observations, this purely formal variance propagation cannot describe the full noise characteristics introduced by the original observations. Therefore, we sophisticate our model by deriving empirical covariances from the residuals of an orbit fit of the kinematic positions. We process GRACE (Gravity Recovery And Climate Experiment) GPS data of April 2007 to derive gravity field solutions up to degree and order 70. Two different orbit parametrisations, a purely dynamic orbit and a reduced-dynamic orbit with constrained piecewise constant accelerations, are adopted. The resulting gravity fields are solved on a monthly basis using daily orbital arcs. Extending the stochastic model from utilising epoch-wise covariance information to an empirical model, leads to a – expressed in terms of formal errors – more realistic gravity field solution.

The core satellite of the Global Precipitation Measurement (GPM) mission provides precipitation observations measured with the Dual-frequency Precipitation Radar (DPR). The precipitation can only be estimated from the radar data, and therefore independent validations using direct precipitation measurements on the ground as a true reference need to be performed. Moreover, the quality and the accuracy of satellite observational data depend on various influencing factors, such as altitude, topography and rainfall type. In this way, a validation may help to minimise those uncertainties. The DPR Level 2 algorithms provide three different sets of radar rain rate estimates: Ku-band-only rain rates, Ka-band-only rain rates, and a product using both the Ku and Ka band. This study presents an evaluation of the three GPM-DPR surface precipitation estimates based on the gridded precipitation data of the WegenerNet, a local-scale terrestrial network of 153 meteorological stations in southeastern Austria. The validation is based on graphical and statistical approaches, using only data where both Ku- and Ka-band measurements are available. The focus lies on the resemblance of the rainfall variability within the whole network and the over- and underestimation of the precipitation through the GPM-DPR. The analysis rests upon 15 rainfall events observed by the GPM-DPR over the WegenerNet in the last 4 years; the meteorological winter is excluded due to technical challenges of snow measurements. The WegenerNet provides between 8 and 12 gauges within each GPM-DPR footprint. Its biases are well studied and corrected; thus, it can be taken as a robust ground reference. This work also includes considerations on the limits of such comparisons between small terrestrial networks with a high density of stations and precipitation observations from a satellite. Our results show that the GPM-DPR estimates basically match with the WegenerNet measurements, but absolute quantities are biased. The three types of radar estimates deliver similar results, where Ku-band and dual-frequency estimates are very close to each other. On a general level, Ka-band precipitation estimates deliver better results due to their greater sensitivity to low rainfall rates.

Abstract Orbit determination of probes visiting Solar System bodies is currently the main source of our knowledge about their internal structure, inferred from the estimate of their gravity field and rotational state. Nongravitational forces acting on the spacecraft need to be accurately included in the dynamical modeling (either explicitly or in the form of empirical parameters) not to degrade the solution and its geophysical interpretation. In this study, we present our recovery of NASA GRAIL orbits and our lunar gravity field solutions up to degree and order 350. We propose a systematic approach to select an optimal parametrization with empirical accelerations and pseudo‐stochastic pulses, by checking their impact against orbit overlaps or, in the case of GRAIL, the very precise inter‐satellite link. We discuss how parametrization choices may differ depending on whether the goal is limited to orbit reconstruction or if it also includes the solution of gravity field coefficients. We validate our setup for planetary geodesy by iterating extended lunar gravity field solutions from pre‐GRAIL gravity fields, and we discuss the impact of empirical parametrization on the interpretation of gravity solutions and of their error bars.

Gene ontology analyses of high-confidence autism spectrum disorder (ASD) risk genes highlight chromatin regulation and synaptic function as major contributors to pathobiology. Our recent functional work in vivo has additionally implicated tubulin biology and cellular proliferation. As many chromatin regulators, including the ASD risk genes ADNP and CHD3, are known to directly regulate both tubulins and histones, we studied the five chromatin regulators most strongly associated with ASD (ADNP, CHD8, CHD2, POGZ and KMT5B) specifically with respect to tubulin biology. We observe that all five localize to microtubules of the mitotic spindle in vitro in human cells and in vivo in Xenopus. Investigation of CHD2 provides evidence that mutations present in individuals with ASD cause a range of microtubule-related phenotypes, including disrupted localization of the protein at mitotic spindles, cell cycle stalling, DNA damage and cell death. Lastly, we observe that ASD genetic risk is significantly enriched among tubulin-associated proteins, suggesting broader relevance. Together, these results provide additional evidence that the role of tubulin biology and cellular proliferation in ASD warrants further investigation and highlight the pitfalls of relying solely on annotated gene functions in the search for pathological mechanisms., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Copy number variants (CNVs) associated with neurodevelopmental disorders are characterized by extensive phenotypic heterogeneity. In particular, one CNV was identified in a subset of children clinically diagnosed with intellectual disabilities (ID) that results in a hemizygous deletion of multiple genes at chromosome 16p12.1. In addition to ID, individuals with this deletion display a variety of symptoms including microcephaly, seizures, cardiac defects, and growth retardation. Moreover, patients also manifest severe craniofacial abnormalities, such as micrognathia, cartilage malformation of the ears and nose, and facial asymmetries; however, the function of the genes within the 16p12.1 region have not been studied in the context of vertebrate craniofacial development. The craniofacial tissues affected in patients with this deletion all derive from the same embryonic precursor, the cranial neural crest, leading to the hypothesis that one or more of the 16p12.1 genes may be involved in regulating neural crest cell (NCC)-related processes. To examine this, we characterized the developmental role of the 16p12.1-affected gene orthologs, polr3e , mosmo , uqcrc2 , and cdr2 , during craniofacial morphogenesis in the vertebrate model system, Xenopus laevis . While the currently-known cellular functions of these genes are diverse, we find that they share similar expression patterns along the neural tube, pharyngeal arches, and later craniofacial structures. As these genes show co-expression in the pharyngeal arches where NCCs reside, we sought to elucidate the effect of individual gene depletion on craniofacial development and NCC migration. We find that reduction of several 16p12.1 genes significantly disrupts craniofacial and cartilage formation, pharyngeal arch migration, as well as NCC specification and motility. Thus, we have determined that some of these genes play an essential role during vertebrate craniofacial patterning by regulating specific processes during NCC development, which may be an underlying mechanism contributing to the craniofacial defects associated with the 16p12.1 deletion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lasser, Bolduc, Murphy, O'Brien, Lee, Girirajan and Lowery.)

We previously identified a deletion on chromosome 16p12.1 that is mostly inherited and associated with multiple neurodevelopmental outcomes, where severely affected probands carried an excess of rare pathogenic variants compared to mildly affected carrier parents. We hypothesized that the 16p12.1 deletion sensitizes the genome for disease, while "second-hits" in the genetic background modulate the phenotypic trajectory. To test this model, we examined how neurodevelopmental defects conferred by knockdown of individual 16p12.1 homologs are modulated by simultaneous knockdown of homologs of "second-hit" genes in Drosophila melanogaster and Xenopus laevis. We observed that knockdown of 16p12.1 homologs affect multiple phenotypic domains, leading to delayed developmental timing, seizure susceptibility, brain alterations, abnormal dendrite and axonal morphology, and cellular proliferation defects. Compared to genes within the 16p11.2 deletion, which has higher de novo occurrence, 16p12.1 homologs were less likely to interact with each other in Drosophila models or a human brain-specific interaction network, suggesting that interactions with "second-hit" genes may confer higher impact towards neurodevelopmental phenotypes. Assessment of 212 pairwise interactions in Drosophila between 16p12.1 homologs and 76 homologs of patient-specific "second-hit" genes (such as ARID1B and CACNA1A), genes within neurodevelopmental pathways (such as PTEN and UBE3A), and transcriptomic targets (such as DSCAM and TRRAP) identified genetic interactions in 63% of the tested pairs. In 11 out of 15 families, patient-specific "second-hits" enhanced or suppressed the phenotypic effects of one or many 16p12.1 homologs in 32/96 pairwise combinations tested. In fact, homologs of SETD5 synergistically interacted with homologs of MOSMO in both Drosophila and X. laevis, leading to modified cellular and brain phenotypes, as well as axon outgrowth defects that were not observed with knockdown of either individual homolog. Our results suggest that several 16p12.1 genes sensitize the genome towards neurodevelopmental defects, and complex interactions with "second-hit" genes determine the ultimate phenotypic manifestation., Competing Interests: The authors have declared that no competing interests exist.

The 1.6 Mbp deletion on chromosome 3q29 is associated with a range of neurodevelopmental disorders, including schizophrenia, autism, microcephaly, and intellectual disability. Despite its importance towards neurodevelopment, the role of individual genes, genetic interactions, and disrupted biological mechanisms underlying the deletion have not been thoroughly characterized. Here, we used quantitative methods to assay Drosophila melanogaster and Xenopus laevis models with tissue-specific individual and pairwise knockdown of 14 homologs of genes within the 3q29 region. We identified developmental, cellular, and neuronal phenotypes for multiple homologs of 3q29 genes, potentially due to altered apoptosis and cell cycle mechanisms during development. Using the fly eye, we screened for 314 pairwise knockdowns of homologs of 3q29 genes and identified 44 interactions between pairs of homologs and 34 interactions with other neurodevelopmental genes. Interestingly, NCBP2 homologs in Drosophila (Cbp20) and X. laevis (ncbp2) enhanced the phenotypes of homologs of the other 3q29 genes, leading to significant increases in apoptosis that disrupted cellular organization and brain morphology. These cellular and neuronal defects were rescued with overexpression of the apoptosis inhibitors Diap1 and xiap in both models, suggesting that apoptosis is one of several potential biological mechanisms disrupted by the deletion. NCBP2 was also highly connected to other 3q29 genes in a human brain-specific interaction network, providing support for the relevance of our results towards the human deletion. Overall, our study suggests that NCBP2-mediated genetic interactions within the 3q29 region disrupt apoptosis and cell cycle mechanisms during development., Competing Interests: The authors have declared that no competing interests exist.

Wolf-Hirschhorn syndrome (WHS) is a rare developmental disorder characterized by intellectual disability and various physical malformations including craniofacial, skeletal, and cardiac defects. These phenotypes, as they involve structures that are derived from the cranial neural crest, suggest that WHS may be associated with abnormalities in neural crest cell (NCC) migration. This syndrome is linked with assorted mutations on the short arm of chromosome 4, most notably the microdeletion of a critical genomic region containing several candidate genes. However, the function of these genes during embryonic development, as well as the cellular and molecular mechanisms underlying the disorder, are still unknown. The model organism Xenopus laevis offers a number of advantages for studying WHS. With the Xenopus genome sequenced, genetic manipulation strategies can be readily designed in order to alter the dosage of the WHS candidate genes. Moreover, a variety of assays are available for use in Xenopus to examine how manipulation of WHS genes leads to changes in the development of tissue and organ systems affected in WHS. In this review article, we highlight the benefits of using X. laevis as a model system for studying human genetic disorders of development, with a focus on WHS.

Neurons depend on the highly dynamic microtubule (MT) cytoskeleton for many different processes during early embryonic development including cell division and migration, intracellular trafficking and signal transduction, as well as proper axon guidance and synapse formation. The coordination and support from MTs is crucial for newly formed neurons to migrate appropriately in order to establish neural connections. Once connections are made, MTs provide structural integrity and support to maintain neural connectivity throughout development. Abnormalities in neural migration and connectivity due to genetic mutations of MT-associated proteins can lead to detrimental developmental defects. Growing evidence suggests that these mutations are associated with many different neurodevelopmental disorders, including intellectual disabilities (ID) and autism spectrum disorders (ASD). In this review article, we highlight the crucial role of the MT cytoskeleton in the context of neurodevelopment and summarize genetic mutations of various MT related proteins that may underlie or contribute to neurodevelopmental disorders.

Open radical cystectomy (ORC) remains the gold standard for treatment of muscle-invasive bladder cancer and certain cases of high-risk noninvasive bladder cancer. However, ORC is associated with significant morbidity, and there is promise of improved outcomes with the emergence of minimally invasive surgery. Because of the increased adoption of robotic radical cystectomy (RRC), we sought to review the current literature on the robotic approach. We explored the surgical techniques, perioperative and postoperative complications, oncologic and functional outcomes, and quality of life of patients with RRC versus ORC. Current data appear to favor RRC in perioperative outcomes and patient recovery, although RRC continues to be associated with longer surgical times and higher costs. Oncologic data are also promising, however data on long-term oncologic outcomes are insufficient. To date, there is evidence of similar functional outcomes between RRC and ORC continence, but there is a paucity of rigorous, standardized studies on health-related quality of life for continent versus incontinent diversion. Even as use of RRC steadily grows, there is a lack of consensus on the type of approach and urinary diversion that is optimal. We assessed the influence of surgeon experience on the totally intracorporeal urinary diversion and its feasibility to be widely adopted. We aimed to answer the question of whether there are significant benefits to RRC, and furthermore, of the effect of the approach on the choice of urinary diversion., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Bowel-related injuries are known complications of suprapubic tube (SPT) catheterization placement. A literature review was conducted to determine identifiable risk factors for bowel injury. Results on the analysis of 25 cases are presented along with a proposed algorithm to aid in choosing between open, percutaneous, and image-guided methods of placement.

Introduction: The application of robotic-assisted radical prostatectomy has increased considerably over the past decade, but there remains a paucity of standardized complications reporting associated with this procedure. The complications literature regarding robotic prostatectomy is wrought with limitations, variability, and bias making meaningful comparisons between surgical series difficult., Materials and Methods: From November 2006 to December 2010, a total of 575 patients were evaluated. Data were assimilated through an IRB-approved blinded prospective database by an independent third party committee. Patients were followed prospectively for 30 days postoperatively. The Modified Clavien system was utilized to grade complications. Grade I and II complications were classified as minor, while grade III, IV, and V were considered major complications. Multiple complications in individual patients were recorded as separate events. Our initial experience and that of our most recent were compared. Age, body mass index, American Society of Anesthesiologists score, Gleason grade, prostate specific antigen, prostate volume, and complications were evaluated., Results: Of the 575 patients, 482 (83.8%) had an ideal perioperative course. In the remaining 93 (16.2%) patients, there were 117 complications. Minor complications occurred in 84 (14.6%) and major complications arose in 15 (2.6%) patients. When the first 500 patients were divided into subsets of 100 patients, a linear regression analysis demonstrated no significant difference in overall complications among the five quintiles (p=0.17). The first quintile was found to have a significantly higher major complication rate compared with the second quintile (p=0.05). The subsequent quintiles exhibited no significant change in major complication rate., Conclusions: As a surgeon progresses through the learning curve, there is a stable overall complication rate with a drop in major complications after the first 100 cases.

In vivo anti-tumor activity of spleen cells from C3H/eb mice bearing a syngeneic fibrosarcoma was shown previously to decline to an undetectable level and be replaced by tumor-enhancing activity as tumor growth proceeds. In the light of our findings that thymocytes in the early stages of thymic processing can bring about tumor enhancement, we postulated that premature release of thymocytes and their accumulation in the spleen might account for the loss of the anti-tumor response. In the present experiments an injection of thymocytes did in fact cancel the anti-tumor response of reactive splenocytes from tumor-bearing mice. In order to determine whether premature thymocyte release occurs naturally in the tumor-bearing animals, we assayed activity of the enzyme TdT (as a marker for thymus cells) in the spleens of these mice during progressive tumor growth. Cells with TdT activity were clearly evident in the spleens of the tumor-bearing animals, were derived from the thymus, and accumulated in parallel to the loss of anti-tumour reactivity.