Identification of aromatic amino acid residues in conserved region VI of the large polymerase of vesicular stomatitis virus is essential for both guanine-N-7 and ribose 2'-O methyltransferases

AbstractNon-segmented negative-sense RNA viruses possess a unique mechanism for mRNA cap methylation. For vesicular stomatitis virus, conserved region VI in the large (L) polymerase protein catalyzes both guanine-N-7 (G-N-7) and ribose 2'-O (2'-O) methyltransferases, and the two methylases share a binding site for the methyl donor S-adenosyl-l-methionine. Unlike conventional mRNA cap methylation, the 2'-O methylation of VSV precedes subsequent G-N-7 methylation. In this study, we found that individual alanine substitutions in two conserved aromatic residues (Y1650 and F1691) in region VI of L protein abolished both G-N-7 and 2'-O methylation. However, replacement of one aromatic residue with another aromatic residue did not significantly affect the methyltransferase activities. Our studies provide genetic and biochemical evidence that conserved aromatic residues in region VI of L protein essential for both G-N-7 and 2'-O methylations. In combination with the structural prediction, our results suggest that these aromatic residues may participate in RNA recognition

Quantitative Method for Network Security Situation Based on Attack Prediction

Multistep attack prediction and security situation awareness are two big challenges for network administrators because future is generally unknown. In recent years, many investigations have been made. However, they are not sufficient. To improve the comprehensiveness of prediction, in this paper, we quantitatively convert attack threat into security situation. Actually, two algorithms are proposed, namely, attack prediction algorithm using dynamic Bayesian attack graph and security situation quantification algorithm based on attack prediction. The first algorithm aims to provide more abundant information of future attack behaviors by simulating incremental network penetration. Through timely evaluating the attack capacity of intruder and defense strategies of defender, the likely attack goal, path, and probability and time-cost are predicted dynamically along with the ongoing security events. Furthermore, in combination with the common vulnerability scoring system (CVSS) metric and network assets information, the second algorithm quantifies the concealed attack threat into the surfaced security risk from two levels: host and network. Examples show that our method is feasible and flexible for the attack-defense adversarial network environment, which benefits the administrator to infer the security situation in advance and prerepair the critical compromised hosts to maintain normal network communication

Solution-processed quasi-two-dimensional perovskite light-emitting diodes using organic small molecular electron transporting layer

In this paper, all-solution-processed LEDs using quasi-two-dimensional perovskites with organic small molecular electron transporting materials (ETMs) are successfully fabricated

Calorimetric evidence for two phase transitions in Ba1−xKxFe2As2 with fermion pairing and quadrupling states

Materials that break multiple symmetries allow the formation of four-fermion condensates above the superconducting critical temperature (T c). Such states can be stabilized by phase fluctuations. Recently, a fermionic quadrupling condensate that breaks the Z 2 time-reversal symmetry was reported in Ba1−xKxFe2As2. A phase transition to the new state of matter should be accompanied by a specific heat anomaly at the critical temperature where Z 2 time-reversal symmetry is broken (TcZ2>Tc). Here, we report on detecting two anomalies in the specific heat of Ba1−xKxFe2As2 at zero magnetic field. The anomaly at the higher temperature is accompanied by the appearance of a spontaneous Nernst effect, indicating the breakdown of Z 2 symmetry. The second anomaly at the lower temperature coincides with the transition to a zero-resistance state, indicating the onset of superconductivity. Our data provide the first example of the appearance of a specific heat anomaly above the superconducting phase transition associated with the broken time-reversal symmetry due to the formation of the novel fermion order

Pushing the Limits of Machine Design: Automated CPU Design with AI

Design activity -- constructing an artifact description satisfying given goals and constraints -- distinguishes humanity from other animals and traditional machines, and endowing machines with design abilities at the human level or beyond has been a long-term pursuit. Though machines have already demonstrated their abilities in designing new materials, proteins, and computer programs with advanced artificial intelligence (AI) techniques, the search space for designing such objects is relatively small, and thus, "Can machines design like humans?" remains an open question. To explore the boundary of machine design, here we present a new AI approach to automatically design a central processing unit (CPU), the brain of a computer, and one of the world's most intricate devices humanity have ever designed. This approach generates the circuit logic, which is represented by a graph structure called Binary Speculation Diagram (BSD), of the CPU design from only external input-output observations instead of formal program code. During the generation of BSD, Monte Carlo-based expansion and the distance of Boolean functions are used to guarantee accuracy and efficiency, respectively. By efficiently exploring a search space of unprecedented size 10^{10^{540}}, which is the largest one of all machine-designed objects to our best knowledge, and thus pushing the limits of machine design, our approach generates an industrial-scale RISC-V CPU within only 5 hours. The taped-out CPU successfully runs the Linux operating system and performs comparably against the human-designed Intel 80486SX CPU. In addition to learning the world's first CPU only from input-output observations, which may reform the semiconductor industry by significantly reducing the design cycle, our approach even autonomously discovers human knowledge of the von Neumann architecture.Comment: 28 page

Prognostic factors and treatment of neuroendocrine tumors of the uterine cervix based on the FIGO 2018 staging system: a single-institution study of 172 patients

Objective This study aimed to explore the prognostic factors and outcomes of patients with neuroendocrine tumors (NETs) of the cervix and to determine appropriate treatment. Methods A single-institution retrospective analysis of 172 patients with NETs was performed based on the new International Federation of Gynecology and Obstetrics (FIGO 2018) staging system. Results Among the 172 eligible patients, 161 were diagnosed with small cell neuroendocrine carcinoma (SCNEC), six with large cell neuroendocrine carcinoma, four with typical carcinoid tumors and one with SCNEC combined with an atypical carcinoid tumor. According to the FIGO 2018 staging guidelines, 31 were stage I, 66 were stage II, 57 were stage III, and 18 were stage IV. The 5-year survival rates of patients with stage I–IV disease were 74.8%, 56.2%, 41.4% and 0%, respectively. The 5-year progression-free survival rates of patients with stage I–IV disease were 63.8%, 54.5%, 30.8% and 0%, respectively. In the multivariate analysis, advanced FIGO stage, large tumor and older age were identified as independent variables for 5-year survival in patients with stage I–IV disease. FIGO stage, tumor size and para-aortic lymph node metastasis were independent prognostic factors for 5-year progression-free survival in patients with stage I–IV disease. For the patients receiving surgery (n = 108), tumor size and pelvic lymph node metastasis were independent prognostic factors for 5-year survival, and pelvic lymph node metastasis for 5-year progression-free survival. In stage IVB, at least six cycles of chemotherapy (n = 7) was associated with significantly better 2-year OS (83.3% vs. 9.1%, p < 0.001) and 2-year PFS (57.1% vs. 0%, p = 0.01) than fewer than six cycles of chemotherapy(n = 11). Conclusion Advanced FIGO stage, large tumor, older age and lymph node metastasis are independent prognostic factors for NETs of the cervix. The TP/TC and EP regimens were the most commonly used regimens, with similar efficacies and toxicities. Standardized and complete multimodality treatment may improve the survival of patients with NETs

Large-scale patterned quantum dots as color conversion layer for organic light emitting diode by inkjet printing

In this work, we fabricated 6.6-inch QD display panel by inkjet printing technology, being cooperated with active matrix organic light emitting diodes (AMOLEDs). Here 3-stack blue OLEDs (BOLEDs) with top-emission structure acted as backlight and red QD layer acted as converted materials, which exhibited high quantum efficiency, high luminance, high color purity and improved wide viewing angle of output emission. We believe that inkjet-printed QD display with AMOLEDs would be promising candidate for the next generation display and lighting in the near future