Hybrid minigene splicing assay verifies the pathogenicity of a novel splice site variant in the COL1A1 gene of a chinese patient with osteogenesis imperfecta type I

Abstract(#br)Background(#br)Osteogenesis imperfecta (OI) is a rare genetic bone disease associated with brittle bones and fractures. Among all known types, OI type I is the most common type and characterized by increased bone fragility, low bone mass, distinctly blue-gray sclera, and susceptibility to conductive hearing loss beginning in adolescence. Mutations in genes encoding type I collagen ( COL1A1 and COL1A2 ) contribute to the main pathogenic mechanism of OI.(#br)Methods(#br)Subtle mutation of the COL1A1 gene in the proband was detected by targeted next-generation sequencing (NGS) and confirmed by Sanger sequencing. We then assessed the effect of the mutation on the splicing of the COL1A1 gene by bioinformatics prediction and hybrid minigene splicing assay (HMSA).(#br)Results(#br)A novel splice site mutation c.1821+1 G > C was discovered in the proband by NGS and further confirmed by Sanger sequencing, which was also simultaneously identified from the proband’s mother and elder sister. Bioinformatics predicted that this mutation would result in a disappearance of the 5′ donor splice site in intron 26, thereby leading to abnormal splicing and generation of premature stop codon. The follow-up experimental data generated by HMSA was consistent with this prediction.(#br)Conclusion(#br)Our study identified a novel splice site mutation that caused OI type I in the proband by abnormal splicing and demonstrated that combined applications of NGS, bioinformatics and HMSA are comprehensive and effective methods for diagnosis and aberrant splicing study of OI

Clinical Value of Spectral Imaging Combined with MAR for CTA after Embolization of Intracranial Aneurysms

Objective: To evaluate the application value of combining spectral imaging and metal artifact reduction (MAR) in head and neck CTA after the embolization of intracranial aneurysms. Methods: We collected 37 patients who experienced embolization of intracranial aneurysms then received spectral imaging of head and neck CTA. Monochromatic images with energy ranging from 70～140 keV, 120 kVp-like mixed energic images, 70～140 keV MAR images, and 120 kVp-like MAR images were generated. The region of interest was placed on the area near the coil and with the most serious metal artifact. CT attenuation and standard deviation were measured, and artifact index (AI) and signal-noise ratio (SNR) were calculated. Two radiologists independently subjectively evaluated the metal artifact and the display of surrounding vessels using Likert 5 scales. The subjective scores and objective parameters between MAR and non-MAR images were compared. The Wilcoxon ranking test, paired sample t test, and independent sample t test were utilized to compare parameters between the groups. Results: MAR images had significantly lower AI than did non-MAR images for all eight monochromatic energies. When energies ranged from 80~110 keV, SNR was higher for MAR images than for non-MAR images, and the difference was statistically significant. With same energies, MAR images had higher artifact and vessel display scores than did non-MAR images. For non-MAR images, the different coil diameters did not make a statistical difference in AI and vessel display scores. For MAR images, a larger coil diameter (>8.79 mm) led to higher AI and lower vessel display scores than did normal diameters (≤8.79 mm). Conclusion: The combination of spectral imaging and MAR could effectively reduce the metal artifact of implants for the embolization of intracranial aneurysms and improve the surrounding vessel display. Moreover, the metal artifact reduction effect was more significant for the coils with smaller diameters

Separating VNF and Network Control for Hardware‐Acceleration of SDN/NFV Architecture

A hardware‐acceleration architecture that separates virtual network functions (VNFs) and network control (called HSN) is proposed to solve the mismatch between the simple flow steering requirements and strong packet processing abilities of software‐defined networking (SDN) forwarding elements (FEs) in SDN/network function virtualization (NFV) architecture, while improving the efficiency of NFV infrastructure and the performance of network‐intensive functions. HSN makes full use of FEs and accelerates VNFs through two mechanisms: (1) separation of traffic steering and packet processing in the FEs; (2) separation of SDN and NFV control in the FEs. Our HSN prototype, built on NetFPGA‐10G, demonstrates that the processing performance can be greatly improved with only a small modification of the traditional SDN/NFV architecture

Direct Conversion of Methane to Propylene

Nonoxidative coupling of methane exhibits promising prospect in that it affords value-added hydrocarbons and hydrogen with high atom economy. However, challenge remains in direct, selective conversion of methane to more valuable hydrocarbons like olefins. The current work presents a catalyst with well-dispersed Ta atoms anchored by graphitic C3N4-supported phthalocyanine. Such a catalyst is able to convert methane selectively to ethylene and propylene at a relatively low temperature (350 °C). The conception of the active center and construction of the catalyst have been described, and the origins of the catalytic performance are discussed

CFD Investigation on Secondary Flow Characteristics in Double-Curved Subsea Pipelines with Different Spatial Structures

Double-curved pipes are widely employed as essential components of subsea pipeline systems. Considering the layout flexibility and application diversity, there are various spatial structures for the double-curved combinations. However, few studies have compared the flow characteristics in different double-curved pipes. The dissipations of the corresponding downstream flow have not been thoroughly investigated, which are crucial for the measurement accuracy and flow assurance. In this paper, the turbulent flow in double-curved pipes with different spatial structures (i.e., Z-, U-, and spatial Z- type) was numerically studied by employing the ω-Reynolds stress model. The major purpose was to develop an in-depth knowledge on the secondary flow characteristics in different double-curved pipes and quantify the dissipations of the downstream flow. The effects of the spatial angle and interval distance of the two curves on the flow fields are taken into consideration, and the swirl intensity Si is introduced to evaluate the secondary flow dissipation. It is found that the secondary flows in the Z- and U-type structures are in opposite directions when the interval distance is short (3D), and the secondary flow in the spatial Z-type exhibits an oblique symmetric form. Only in the Z-type pipe with a short interval distance the secondary flow exhibits an exponential dissipation, and the fully developed flow is easier to achieve than the other cases. However, as the interval distance increases, the directions of the secondary flow in the U- and Z-type structures are the same, and the flow dissipations in all the structures return to the exponential types. The obtained dissipation rates for the secondary flow downstream of Z-, U-, and spatial Z-pipes with the 9D interval distance were 0.40, 0.25, and 0.20, respectively. The results are expected to guide the design of pipeline layouts and provide a reference for the arrangements of flowmeters in a complex subsea pipeline system

CFD Investigation on Secondary Flow Characteristics in Double-Curved Subsea Pipelines with Different Spatial Structures

Double-curved pipes are widely employed as essential components of subsea pipeline systems. Considering the layout flexibility and application diversity, there are various spatial structures for the double-curved combinations. However, few studies have compared the flow characteristics in different double-curved pipes. The dissipations of the corresponding downstream flow have not been thoroughly investigated, which are crucial for the measurement accuracy and flow assurance. In this paper, the turbulent flow in double-curved pipes with different spatial structures (i.e., Z-, U-, and spatial Z- type) was numerically studied by employing the ω-Reynolds stress model. The major purpose was to develop an in-depth knowledge on the secondary flow characteristics in different double-curved pipes and quantify the dissipations of the downstream flow. The effects of the spatial angle and interval distance of the two curves on the flow fields are taken into consideration, and the swirl intensity Si is introduced to evaluate the secondary flow dissipation. It is found that the secondary flows in the Z- and U-type structures are in opposite directions when the interval distance is short (3D), and the secondary flow in the spatial Z-type exhibits an oblique symmetric form. Only in the Z-type pipe with a short interval distance the secondary flow exhibits an exponential dissipation, and the fully developed flow is easier to achieve than the other cases. However, as the interval distance increases, the directions of the secondary flow in the U- and Z-type structures are the same, and the flow dissipations in all the structures return to the exponential types. The obtained dissipation rates for the secondary flow downstream of Z-, U-, and spatial Z-pipes with the 9D interval distance were 0.40, 0.25, and 0.20, respectively. The results are expected to guide the design of pipeline layouts and provide a reference for the arrangements of flowmeters in a complex subsea pipeline system