POLR3-related leukodystrophy caused by biallelic POLR3A and 1C pathogenic variants: a single-center experience

ObjectivesThis study aimed to investigate the clinical, radiological, and genetic features of POLR3-related leukodystrophy caused by mutations in POLR3A or POLR1C.MethodsFourteen Chinese patients with POLR3-related leukodystrophy were enrolled in this cross-sectional observational study. The clinical manifestations, brain MRI and genetic tests of the patients were evaluated.ResultsThirteen patients had biallelic variants in POLR3A (92.9%), and one had biallelic variants in POLR1C (7.1%). The median age at disease onset was 9 months. A total of 85.7% of the patients presented with motor delay, abnormal gait, and intelligence disability in the first 2 years of life. Intellectual disability can be categorized based on its severity. It varied from mild (which involves difficulty concentrating) to very severe (with no smiling or laughing or never being able to speak since birth). Short stature was observed in all patients, and delayed dentition was observed in 64.3% of them. Furthermore, three out of 14 patients had myopia. Hypomyelination was invariably present in all patients, whereas myelination of the basal ganglia was preserved in only six out of 14 patients. All the mutations were compound heterozygous and included missense (n = 25), deletion (n = 1), and splice site variants (n = 2). A total of 78.6% of the patients with POLR3A were identified as carrying the c.1771-6C>G variant or the c.1771-7C>G variant.ConclusionThe phenotypic diversity of POLR3-HLD associated with pathogenic variants ranges from mild to very severe for neurological and non-neurological symptoms. Most patients presented symptoms in the first 2 years of life. The c.1771-6C>G or c.1771-7C>G variant is the most frequent mutation site in POLR3A in Chinese individuals

Discrepancy between bulk-rock and zircon Hf isotopes accompanying Nd-Hf isotope decoupling

Zircon is an important accessory mineral for studying the crust-mantle interaction and crustal growth through time because zircon crystals not only allow precise dating but also record initial Hf isotope ratios of the host magmas. Our study on a suite of gabbronorite, mafic diorite cumulates, diorite and granite from the Kekeli Batholith in the North Qilian Orogenic Belt, northern Tibetan Plateau, shows (1) a significant Hf isotope discrepancy between zircons and their bulk rocks; and (2) bulk-rock Nd-Hf isotopic decoupling. These observations thus demonstrate that zircons do not always capture the full history of magmatic system. The significant positive correlation between bulk-rock Hf isotope ratios and TiO2 content (R2=0.94) indicates that Ti-rich minerals (e.g., ilmenite, amphibole) are likely important Hf hosts. The early-formed Ti-rich minerals possibly record different Hf isotopes from those of zircons crystallized subsequently, thus causing discrepancy between zircons and bulk-rocks and leading to bulk-rock Nd-Hf isotope decoupling. Correlations between bulk-rock TiO2 content, Mg isotopes and Hf isotopes indicate a mixing process, with granite and gabbronorite representing two compositional endmembers. Because Ti minerals have higher crystallization temperatures than zircons, when the mixing melts have contrasting isotopes (or from heterogeneous sources/ have a strong crustal contamination), the bulk-rock and zircon Hf isotope discrepancies reflect mineral crystallization sequence during mafic and felsic magma mixing. It is thus imperative to consider early formed minerals such as Ti-rich minerals and the bulk rock composition, not just zircons, when using Hf isotopes to track melt evolution and precisely constrain mantle contribution to granitoid petrogenesis

Numerical Simulation on Damage and Failure Mechanism of Rock under Combined Multiple Strain Rates

During underground hard-rock mining, the drilling and blasting method currently remains the most economical excavation method, and the rock may experience a multistrain-rate spectrum under quasi-static, dynamic, and rheological loading conditions and their combination as well. The study on the damage mechanism of rock under multistrain-rate condition that induced by mining excavation is the fundamental issue for predicting the mining-induced hazards such as rockburst. In this study, the state of the art of rock damage and failure under different strain rates is reviewed first. Then, the numerical model for rock failure under multiple strain rates is formulated when the rock damage is taken as the main thread. Meanwhile, we summarize our work in this area over the past ten years, and the constitutive law for the damage and failure of rock under multistrain rates is presented. Finally, several numerical examples, i.e., rock damage and failure under combined static and dynamic load, rock damage and failure triggered by dynamic stress redistribution due to excavation, rock damage and failure induced by blasting, and rock damage and failure due to the combination of dynamic disturbance and rheological load, are presented. Based on these numerical simulations, the associated rock damage mechanism and failure behaviors under differently combined multiple strain rates are clarified, which may provide a theoretical basis for clarifying the rock failure mechanism during rockbursts and rock blasting. Also, further studies on the damage and failure of rock under multiple strain rates are suggested

The primary stability of different implants for intra-articular calcaneal fractures: an in vitro study

Abstract Background Calcaneal fractures account for around 2% of all fractures and most of them are intra-articular fractures. Many implants have been used in the fixation of calcaneal fractures, but their biomechanical stability has not yet been well investigated. The aim of this study was to compare the primary stability of four fixations of calcaneal fracture. Methods Eight cadaveric calcaneus samples were used to simulate the Sanders’ types III fracture pattern and fixed through four different implants, namely, K-wires, cannulated screws (CS), absorbable screws (AS), and plate-screw system (PSS). Each specimen was then placed into a custom-made jig and was loaded through a material testing machine to simulate the physiological condition. The primary stability was measured in the vertical direction as the stiffness and anterior–posterior direction as the calcaneocuboid force. One-way analysis of variance was used for data analysis. Results The results showed the highest stiffness of 634 (383–891; SD 226) N/mm in the intact model. It was significantly higher than the models fixed with K-wires, CS or PSS. There was no significant difference in vertical stiffness between fractures fixed with AS and the intact model or other fixed models. The intact model showed the lowest calcaneocuboid force of 153 (120–218; SD 39) N, while the fractures fixed with AS showed the greatest force of 242 (146–398; SD 84) N. The significance was only detected between these two models. Conclusions The global stiffness was similar when the calcaneal fractures were fixed by K-wires, CS and PSS. The stability of the AS fixation differed along both the vertical and anterior–posterior directions, and was greatly influenced by the bone quality. AS for fracture fixation should be designed with greater strength and pull-out resistance

Continuous Tracking of Targets for Stereoscopic HFSWR Based on IMM Filtering Combined with ELM

High frequency surface wave radar (HFSWR) plays an important role in marine surveillance on account of its ability to provide wide-range early warning detection. However, vessel target track breakages are common in large-scale marine monitoring, which limits the continuous tracking ability of HFSWR. The following are the possible reasons for track fracture: highly maneuverable vessels, dense channels, target occlusion, strong clutter/interference, long sampling intervals, and low detection probabilities. To solve this problem, we propose a long-term continuous tracking method for multiple targets with stereoscopic HFSWR based on an interacting multiple model extended Kalman filter (IMMEKF) combined with an extreme learning machine (ELM). When the trajectory obtained by IMMEKF breaks, a new section of the track will start on the basis of the observation data. For multiple-target tracking, a number of broken tracks can be obtained by IMMEKF tracking. Then the ELM classifies the segments from the same vessel by extracting different features including average velocity, average curvature, ratio of the arc length to the chord length, and wavelet coefficient. Both the simulation and the field experiment results validate the method presented here, showing that this method can achieve long-term continuous tracking for multiple vessels, with an average correct track segment association rate of over 91.2%, which is better than the tracking performance of conventional algorithms, especially when the vessels are in dense channels and strong clutter/interference area

A Performance Evaluation Scheme for Multiple Object Tracking with HFSWR

High-frequency surface wave radar (HFSWR) can detect and continuously track ship objects in real time and beyond the horizon. When ships navigate in a sea area, their motions in a time period form a scenario. The diversity and complexity of the motion scenarios make it difficult to accurately track ships, in which failures such as track fragmentation (TF) are frequently observed. However, it is still unclear how and to what degrees the motions of ships affect the tracking performance, especially which motion patterns can cause tracking failures. This paper addresses this problem and attempts to undertake a first step towards providing an intensive quantitative performance assessment and vulnerability detection scheme for ship-tracking algorithms by proposing an evolutionary and data-mining-based approach. Low-dimensional scenarios in terms of multiple maneuvering ship objects are generated using a grammar-based model. Closed-loop feedback is introduced using evolutionary computation to efficiently collect scenarios that cause more and more tracking performance loss, which provides diversified cases for analysing using data-mining technique to discover indicators of tracking vulnerability. Results on different tracking algorithms show that more cluster and convergence patterns and longer duration of our convoy and cluster patterns in the scenarios can cause severer TF to HFSWR ship tracking

Lognormal-Based Sampling for Fission Product Yields Uncertainty Propagation in Pebble-Bed HTGR

Uncertainty analyses of fission product yields are indispensable in evaluating reactor burnup and decay heat calculation credibility. Compared with neutron cross section, there are fewer uncertainty analyses conducted and it has been a controversial topic by lack of properly estimated covariance matrix as well as adequate sampling method. Specifically, the conventional normal-based sampling method in sampling large uncertainty independent fission yields could inevitably generate nonphysical negative samples. Cutting off these samples would introduce bias into uncertainty results. Here, we evaluate thermal neutron-induced U-235 independent fission yields covariance matrix by the Bayesian updating method, and then we use lognormal-based sampling method to overcome the negative fission yields samples issue. Fission yields uncertainty contribution to effective multiplication factor and several fission products’ atomic densities at equilibrium core of pebble-bed HTGR are quantified and investigated. The results show that the lognormal-based sampling method could prevent generating negative yields samples and maintain the skewness of fission yields distribution. Compared with the zero cut-off normal-based sampling method, the lognormal-based sampling method evaluates the uncertainty of effective multiplication factor and atomic densities are larger. This implies that zero cut-off effect in the normal-based sampling method would underestimate the fission yields uncertainty contribution. Therefore, adopting the lognormal-based sampling method is crucial for providing reliable uncertainty analysis results in fission product yields uncertainty analysis

Motion Parameter Identification and Motion Compensation for Shipborne HFSWR by Using the Reference RF Signal Generated at the Shore

The shipborne high-frequency surface wave radar (HFSWR) platform produces six degrees of freedom (DOF) motion at sea, which affects the performance of radar target detection and remote sensing of ocean surface dynamics parameters. Motion compensation can mitigate the effect of six-DOF motion, but motion parameters (including amplitude and angular frequency) need to be known. Motion parameters obtained by using high precision sensors are affected by the precision error and time delay, thus affecting the effect of motion compensation. To obtain the motion parameters accurately and in real time, a method of identifying the motion parameters by using an artificially transmitted reference radio frequency (RF) signal generated at the shore is proposed. Based on the results of the parameter identification, the reference RF signal and the first-order radar cross-sections (RCSs) modulated by six-DOF motion of the shipborne HFSWR platform can be compensated. The identification of angular frequency is divided into two steps: (1) Preliminary identification results are obtained by using the reference RF signal; (2) the pattern search method is used to further improve the identification accuracy of angular frequency. The amplitude of translation (including surge and sway) can be identified accurately through the reference RF signal. Due to the small amplitude of rotation (including roll, pitch, and yaw), it needs to be identified by the reference RF signal and pattern search method. After identifying the motion parameters, division in the time domain is used for motion compensation. Through the simulation results, both translation and rotation have good motion compensation effects. In addition, the method of using high precision sensors to obtain motion parameters and compensation is compared with the method in this paper, the simulation results of motion compensation show that the latter is better

A New Precursor Integral Method for Solving Space-Dependent Kinetic Equations in Neutronic and Thermal-Hydraulic Coupling System

The accurate prediction of the neutronic and thermal-hydraulic coupling system transient behavior is important in nuclear reactor safety analysis, where a large-scale nonlinear coupling system with strong stiffness should be solved efficiently. In order to reduce the stiffness and huge computational cost in the coupling system, the high-performance numerical techniques for solving delayed neutron precursor equation are a key issue. In this work, a new precursor integral method with an exponential approximation is proposed and compared with widely used Taylor approximation-based precursor integral methods. The truncation errors of exponential approximation and Taylor approximation are analyzed and compared. Moreover, a time control technique is put forward which is based on flux exponential approximation. The procedure is tested in a 2D neutron kinetic benchmark and a simplified high-temperature gas-cooled reactor-pebble bed module (HTR-PM) multiphysics problem utilizing the efficient Jacobian-free Newton–Krylov method. Results show that selecting appropriate flux approximation in the precursor integral method can improve the efficiency and precision compared with the traditional method. The computation time is reduced to one-ninth in the HTR-PM model under the same accuracy when applying the exponential integral method with the time adaptive technique