Identification of <em>CHIP</em> as a novel causative gene for autosomal recessive cerebellar ataxia

Autosomal recessive cerebellar ataxias are a group of neurodegenerative disorders that are characterized by complex clinical and genetic heterogeneity. Although more than 20 disease-causing genes have been identified, many patients are still currently without a molecular diagnosis. In a two-generation autosomal recessive cerebellar ataxia family, we mapped a linkage to a minimal candidate region on chromosome 16p13.3 flanked by single-nucleotide polymorphism markers rs11248850 and rs1218762. By combining the defined linkage region with the whole-exome sequencing results, we identified a homozygous mutation (c.493CT) in CHIP (NM_005861) in this family. Using Sanger sequencing, we also identified two compound heterozygous mutations (c.389AT/c.441GT; c.621C>G/c.707GC) in CHIP gene in two additional kindreds. These mutations co-segregated exactly with the disease in these families and were not observed in 500 control subjects with matched ancestry. CHIP colocalized with NR2A, a subunit of the N-methyl-D-aspartate receptor, in the cerebellum, pons, medulla oblongata, hippocampus and cerebral cortex. Wild-type, but not disease-associated mutant CHIPs promoted the degradation of NR2A, which may underlie the pathogenesis of ataxia. In conclusion, using a combination of whole-exome sequencing and linkage analysis, we identified CHIP, encoding a U-box containing ubiquitin E3 ligase, as a novel causative gene for autosomal recessive cerebellar ataxia

Case Report: Cancer spectrum and genetic characteristics of a de novo germline POLD1 p.L606M variant-induced polyposis syndrome

Germline variations in the DNA polymerase genes, POLE and POLD1, can lead to a hereditary cancer syndrome that is characterized by frequent gastrointestinal polyposis and multiple primary malignant tumors. However, because of its rare occurrence, this disorder has not been extensively studied. In this report, we present the case of a 22-year-old female patient who had been diagnosed with gastrointestinal polyposis, breast fibroadenoma, multiple primary colorectal cancers, and glioblastoma (grade IV) within a span of 4 years. Next-generation sequencing analysis revealed a germline variant in POLD1 (c.1816C&gt;A; p.L606M). In silico analysis using protein functional predicting software, including SIFT, Polyphen, GERP++, and CADD, further confirmed the pathogenicity of POLD1 p.L606M (classified as ACMG grade Class 4). In line with polymerase deficiency, both rectal cancer and glioblastoma tissues exhibited a high tumor mutation burden, with 16.9 muts/Mb and 347.1 muts/Mb, respectively. Interestingly, the patient has no family history of cancer, and gene examination of both parents confirms that this is a de novo germline variant. Therefore, molecular screening for POLD1 may be necessary for patients with such a cancer spectrum, regardless of their family history

Study on the Dynamics of Laser Gyro Strapdown Inertial Measurement Unit System Based on Transfer Matrix Method for Multibody System

The dynamic test precision of the strapdown inertial measurement unit (SIMU) is the basis of estimating accurate motion of various vehicles such as warships, airplanes, spacecrafts, and missiles. So, it is paid great attention in the above fields to increase the dynamic precision of SIMU by decreasing the vibration of the vehicles acting on the SIMU. In this paper, based on the transfer matrix method for multibody system (MSTMM), the multibody system dynamics model of laser gyro strapdown inertial measurement unit (LGSIMU) is developed; the overall transfer equation of the system is deduced automatically. The computational results show that the frequency response function of the LGSIMU got by the proposed method and Newton-Euler method have good agreements. Further, the vibration reduction performance and the attitude error responses under harmonic and random excitations are analyzed. The proposed method provides a powerful technique for studying dynamics of LGSIMU because of using MSTMM and its following features: without the global dynamics equations of the system, high programming, low order of system matrix, and high computational speed

Dynamic Power Flow Cascading Failure Analysis of Wind Power Integration with Complex Network Theory

The impact of the rapid development of large-scale centralized wind power farms on the power system is drawing more and more attention. Some topics about grid-connected wind power are discussed from the view of complex network theory in this paper. Firstly, a complex network cascading failure model is established, combined with dynamic AC power flow (DACPF). Then, the IEEE 30 bus system is used to analyze its validity using the simulations of nodes removal, wind power integration, as well as the change of current and voltage boundaries. Furthermore, the influences of wind power before and after smoothing are investigated. Also, different wind power coupling locations are studied. Finally, some significant conclusions are obtained to provide references for large-scale wind power integration

Selective Hydrogenolysis of Glycerol over Acid-Modified Co–Al Catalysts in a Fixed-Bed Flow Reactor

In this study, different acid-modified Co–Al catalysts were prepared and employed for glycerol hydrogenolysis by the addition of B, Ce, Zr, and heteropolyacids (HSiW, HPW, HPMo) to Co–Al catalysts. The catalysts prepared in this work were thoroughly examined by various characterization methods such as BET, ICP, SEM, H₂ chemisorption, TEM, XRD, H₂-TPR, NH₃-TPD, XPS, and FTIR. The results showed an increase in the acid strength and Co dispersion on the catalytic surface for the modified Co–Al catalysts. This facilitated the conversion of glycerol. When ethanol was used as a solvent, the selectivity of 1,2-propanediol (1,2-PDO) by the acid-modified Co–Al catalysts decreased slightly, attributable to the enhanced etherification activity of glycerol with ethanol. However, when water was used as a solvent, the modified Co–Al catalyst with the B, Ce, and Zr species increased the selectivity of 1,2-PDO. Addition of heteropolyacids to the Co–Al catalyst enhanced the selectivity of 1,3-propanediol (1,3-PDO) as compared to 1,2-PDO selectivity which was relatively low due to its association with Brønsted acid sites on the modified Co–Al catalysts. The optimal HSiW/Co–Al catalyst (in terms of both 1,2- and 1,3-PDO selectivity) showed 76.3% glycerol conversion and 18.3% 1,3-PDO selectivity with a good stability. This could be attributed to the existence of well-dispersed Co particles with strong interaction between Co and W species