Caenorhabditis elegans Protein Arginine Methyltransferase PRMT-5 Negatively Regulates DNA Damage-Induced Apoptosis

Arginine methylation of histone and non-histone proteins is involved in transcription regulation and many other cellular processes. Nevertheless, whether such protein modification plays a regulatory role during apoptosis remains largely unknown. Here we report that the Caenorhabditis elegans homolog of mammalian type II arginine methyltransferase PRMT5 negatively regulates DNA damage-induced apoptosis. We show that inactivation of C. elegans prmt-5 leads to excessive apoptosis in germline following ionizing irradiation, which is due to a CEP-1/p53–dependent up-regulation of the cell death initiator EGL-1. Moreover, we provide evidence that CBP-1, the worm ortholog of human p300/CBP, functions as a cofactor of CEP-1. PRMT-5 forms a complex with both CEP-1 and CBP-1 and can methylate the latter. Importantly, down-regulation of cbp-1 significantly suppresses DNA damage-induced egl-1 expression and apoptosis in prmt-5 mutant worms. These findings suggest that PRMT-5 likely represses CEP-1 transcriptional activity through CBP-1, which represents a novel regulatory mechanism of p53-dependent apoptosis

Challenges and Opportunities for Multi-functional Oxide Thin Films for Voltage Tunable Radio Frequency/Microwave Components

There has been significant progress on the fundamental science and technological applications of complex oxides and multiferroics. Among complex oxide thin films, barium strontium titanate (BST) has become the material of choice for room-temperature-based voltage-tunable dielectric thin films, due to its large dielectric tunability and low microwave loss at room temperature. BST thin film varactor technology based reconfigurable radio frequency (RF)/microwave components have been demonstrated with the potential to lower the size, weight, and power needs of a future generation of communication and radar systems. Low-power multiferroic devices have also been recently demonstrated. Strong magneto-electric coupling has also been demonstrated in different multiferroic heterostructures, which show giant voltage control of the ferromagnetic resonance frequency of more than two octaves. This manuscript reviews recent advances in the processing, and application development for the complex oxides and multiferroics, with the focus on voltage tunable RF/microwave components. The over-arching goal of this review is to provide a synopsis of the current state-of the-art of complex oxide and multiferroic thin film materials and devices, identify technical issues and technical challenges that need to be overcome for successful insertion of the technology for both military and commercial applications, and provide mitigation strategies to address these technical challenges

Software-Hardware Co-design for Fast and Scalable Training of Deep Learning Recommendation Models

Deep learning recommendation models (DLRMs) are used across many business-critical services at Facebook and are the single largest AI application in terms of infrastructure demand in its data-centers. In this paper we discuss the SW/HW co-designed solution for high-performance distributed training of large-scale DLRMs. We introduce a high-performance scalable software stack based on PyTorch and pair it with the new evolution of Zion platform, namely ZionEX. We demonstrate the capability to train very large DLRMs with up to 12 Trillion parameters and show that we can attain 40X speedup in terms of time to solution over previous systems. We achieve this by (i) designing the ZionEX platform with dedicated scale-out network, provisioned with high bandwidth, optimal topology and efficient transport (ii) implementing an optimized PyTorch-based training stack supporting both model and data parallelism (iii) developing sharding algorithms capable of hierarchical partitioning of the embedding tables along row, column dimensions and load balancing them across multiple workers; (iv) adding high-performance core operators while retaining flexibility to support optimizers with fully deterministic updates (v) leveraging reduced precision communications, multi-level memory hierarchy (HBM+DDR+SSD) and pipelining. Furthermore, we develop and briefly comment on distributed data ingestion and other supporting services that are required for the robust and efficient end-to-end training in production environments

Clinical manifestation and genetic analysis in Chinese early onset X‐linked retinoschisis

Abstract Background X‐linked retinoschisis (XLRS) is one type of retinal dystrophy leading to the schisis of the neural retina and causing reduced visual acuity. The study aimed to investigate the clinical manifestations and retinoschisin 1 (RS1) mutations in Chinese patients with early onset XLRS. Methods Thirty‐eight probands with early onset XLRS were recruited, comprehensive ophthalmic examination was performed. A targeted gene panel was used to test the RS1 mutations. Results All probands had RS1 hemizygous mutations including 16 known and 14 novel mutations. The median onset age was 2 years old (range 0.1–6 years). Probands with onset age ≤1 years. had more complications (retinal detachment and vitreous hemorrhage, p 1 years. Macular and peripheral involvement was present in 77.27% of probands, and inner and outer nuclear layer splitting were present in 53.57% of probands. Electroretinography showed an electronegative waveform. The relatively rare phenotypes of lamellar macular hole and macular hole were present in a unilateral eye in three probands. Conclusion In conclusion, the early onset XLRS developed more severe complications which need close monitoring and clinical manifestations illustrated here may facilitate the early diagnosis of retinoschisis

Microstructure and storage properties of low V-containing Ti–Cr–V hydrogen storage alloys prepared by arc melting and suction casting

The microstructure and hydrogen storage properties of low V content (Ti_(0.46)Cr_(0.54))_(100?x) V_x (x = 2.5–7.1, at%) and (Ti_y Cr_(1?y))_(95)V_5 (y = 0.38–0.54) alloys were investigated. These alloys were prepared by arc melting and copper mould suction casting. The structures of as-cast (Ti_(0.46)Cr_(0.54))_(100?x) V_x (x = 2.5, 5.0, and 7.1) alloy ingots evolve with V contents from pure Laves- (x = 2.5) to dual-phase TiCr2-BCC structures (5.0 and 7.1), whereas the suction-cast (Ti_(0.46)Cr_(0.54))_(100?x) V_x (x = 2.5, 5.0, and 7.1) alloys only contain single BCC phase. The suction-cast alloy rod (Ti_(0.46)Cr_(0.54))_(95)V_5, containing only 5.0 at% V is shown to possess the optimum hydrogen absorption capacity, with the maximum hydrogen content of 3.14 wt%. Furthermore, the hydrogen storage properties of the suction-cast low V alloys (Ti_y Cr_(1?y))_(95)V)5 (y = 0.38–0.54) are sensitive to Ti/Cr ratios and only those alloys with Ti/Cr ratios close to the CN14 cluster Ti_7Cr_8 have good hydrogen storage properties

Microstructure and storage properties of low V-containing Ti–Cr–V hydrogen storage alloys prepared by arc melting and suction casting

The microstructure and hydrogen storage properties of low V content (Ti_(0.46)Cr_(0.54))_(100?x) V_x (x = 2.5–7.1, at%) and (Ti_y Cr_(1?y))_(95)V_5 (y = 0.38–0.54) alloys were investigated. These alloys were prepared by arc melting and copper mould suction casting. The structures of as-cast (Ti_(0.46)Cr_(0.54))_(100?x) V_x (x = 2.5, 5.0, and 7.1) alloy ingots evolve with V contents from pure Laves- (x = 2.5) to dual-phase TiCr2-BCC structures (5.0 and 7.1), whereas the suction-cast (Ti_(0.46)Cr_(0.54))_(100?x) V_x (x = 2.5, 5.0, and 7.1) alloys only contain single BCC phase. The suction-cast alloy rod (Ti_(0.46)Cr_(0.54))_(95)V_5, containing only 5.0 at% V is shown to possess the optimum hydrogen absorption capacity, with the maximum hydrogen content of 3.14 wt%. Furthermore, the hydrogen storage properties of the suction-cast low V alloys (Ti_y Cr_(1?y))_(95)V)5 (y = 0.38–0.54) are sensitive to Ti/Cr ratios and only those alloys with Ti/Cr ratios close to the CN14 cluster Ti_7Cr_8 have good hydrogen storage properties

Novel Compound Heterozygous BBS2 and Homozygous MKKS Variants Detected in Chinese Families with Bardet–Biedl Syndrome

Background. Bardet–Biedl syndrome (BBS) is a rare multisystem developmental disorder. In this study, we report the genetic causes and clinical manifestations in two Chinese families with BBS. Materials and Methods. Two families were recruited in this study. Family A was a four-generation family with four affected and 15 unaffected members participating in the study, and family B was a consanguineous family with one affected and three unaffected members participating. Whole exome sequencing was performed in the two families, followed by a multistep bioinformatics analysis. Sanger sequencing was used to verify the variants and to perform a segregation analysis. Comprehensive ocular and systemic examinations were also conducted. Results. Novel compound heterozygous variants c.235T > G (p.T79P) and c.534 + 1G > T were detected in the BBS2 gene in family A, and known homozygous variant c.748G > A (p.G250R) was detected in the MKKS gene in family B. Both families presented with retinitis pigmentosa; however, except for polydactyly, all other systemic manifestations were different. All of the affected family members in family A were overweight with a high body mass index (range from 26.5 to 41.9) and high blood pressure. Family A also presented with a delay in the onset of secondary sex characteristics and genital anomalies, while other systemic abnormalities were absent in family B. Conclusions. This study presents one family with two novel BBS2 variants, expanding the variant spectrum of BBS, and one family with a known homozygous MKKS variant. The different phenotypes seen between the families with BBS2 and MKKS variants will contribute to the literature and our overall understanding of BBS