The construction and characterization of the bi-directional promoter between pp38 gene and 1.8-kb mRNA transcripts of Marek's disease viruses

<p>Abstract</p> <p>Background</p> <p>Marek's disease virus (MDV) has a bi-directional promoter between pp38 gene and 1.8-kb mRNA transcripts. By sequencing for the promoters from 8 different strains (CVI988, 814, GA, JM, Md5, G2, RB1B and 648A), it is found, comparing with the other 7 MDV strains, CVI988 has a 5-bp (from -628 to -632) deletion in this region, which caused a Sp1 site destroyed. In order to analysis the activity of the promoter, the complete bi-directional promoters from GA and CVI988 were, respectively, cloned into pCAT-Basic vector in both directions for the recombinants pP_GA(pp38)-CAT, pP_GA(1.8 kb)-CAT, pP_CVI(pp38)-CAT and pP_CVI(1.8 kb)-CAT. The complete promoter of GA was divided into two single-direction promoters from the replication of MDV genomic DNA, and cloned into pCAT-Basic for pdP_GA(pp38)-CAT and pdP_GA(1.8 kb)-CAT as well. The above 6 recombinants were then transfected into chicken embryo fibroblasts (CEFs) infected with MDV, and the activity of chloramphenicol acetyltransferase (CAT) was measured from the lysed CEFs 48 h post transfection.</p> <p>Results</p> <p>The results showed the activity of the divided promoters was decreased on both directions. In 1.8-kb mRNA direction, it is nearly down to 2.4% (19/781) of the whole promoter, while it keeps 65% (34/52) activity in pp38 direction. The deletion of Sp1 site in CVI988 causes the 20% activity decreased, and has little influence in pp38 direction.</p> <p>Conclusion</p> <p>The present study confirmed their result, and the promoter for the 1.8-kb mRNA transcripts is a much stronger promoter than that in the orientation for pp38.</p

Polar Coding for Ring-LWE-Based Public Key Encryption

Cryptographic constructions based on $\textit{ring learning with errors}$ (RLWE) have emerged as one of the front runners for the standardization of post quantum public key cryptography. As the standardization process continues, optimizing specific parts of proposed schemes becomes a worthwhile endeavor. In this work we focus on using error correcting codes to alleviate a natural trade-off present in most schemes; namely, we would like a wider error distribution to increase security, but a wider error distribution comes at the cost of an increased probability of decryption error. The motivation of this work is to improve the security level of RLWE-based public key encryption (PKE) while keeping the target decryption failure rate (DFR) achievable using error-correcting codes. Specifically, we explore how to implement a family member of error correcting codes, known as polar codes, in RLWE-based PKE schemes in order to effectively lower the DFR. The dependency existing in the additive noise term is handled by mapping every error term (e.g., $e,t,s,e_1,e_2$) under canonical embedding to the space $H$ where a product in the number field $K$ gives rise to a coordinate-wise product in $H$. An attempt has been made to make the modulation constellation (message basis) fit in with the canonical basis. Furthermore, we exploit the actuality of some error terms known by the decoder to further lower the DFR. Using our method, the DFR is expected to be as low as $2^{-298}$ for code rate 0.25, $n=1024,q=12289$ and binomial parameter $k=8$ as is exactly the setting of the post-quantum scheme NewHope; DFR is $2^{-156}$ for code rate 0.25, $n=1024,q=12289,k=16$. This new DFR margin enables us to improve the security level by $9.4\%$ compared with NewHope. Moreover, polar encoding and decoding have quasi-linear complexity $O(N\log N)$ and they can be implemented in constant time

Polar Sampler: A Novel Bernoulli Sampler Using Polar Codes with Application to Integer Gaussian Sampling

Cryptographic constructions based on hard lattice problems have emerged as a front runner for the standardization of post quantum public key cryptography. As the standardization process takes place, optimizing specific parts of proposed schemes, e.g., Bernoulli sampling and integer Gaussian sampling, becomes a worthwhile endeavor. In this work, we propose a novel Bernoulli sampler based on polar codes, dubbed ``polar sampler . The polar sampler is information theoretically optimum in the sense that the number of uniformly random bits it consumes approaches the entropy bound asymptotically. It also features quasi-linear complexity and constant-time implementation. An integer Gaussian sampler is developed using multilevel polar samplers. Our algorithm becomes effective when sufficiently many samples are required at each query to the sampler. Security analysis is given based on Kullback-Leibler divergence and R\\u27enyi divergence. Experimental and asymptotic comparisons between our integer Gaussian sampler and state-of-the-art samplers verify its efficiency in terms of entropy consumption, running time and memory cost. We envisage that the proposed Bernoulli sampler can find other applications in cryptography in addition to Gaussian sampling

Bioactive conformational generation of small molecules: A comparative analysis between force-field and multiple empirical criteria based methods

<p>Abstract</p> <p>Background</p> <p>Conformational sampling for small molecules plays an essential role in drug discovery research pipeline. Based on multi-objective evolution algorithm (MOEA), we have developed a conformational generation method called Cyndi in the previous study. In this work, in addition to Tripos force field in the previous version, Cyndi was updated by incorporation of MMFF94 force field to assess the conformational energy more rationally. With two force fields against a larger dataset of 742 bioactive conformations of small ligands extracted from PDB, a comparative analysis was performed between pure force field based method (FFBM) and multiple empirical criteria based method (MECBM) hybrided with different force fields.</p> <p>Results</p> <p>Our analysis reveals that incorporating multiple empirical rules can significantly improve the accuracy of conformational generation. MECBM, which takes both empirical and force field criteria as the objective functions, can reproduce about 54% (within 1Å RMSD) of the bioactive conformations in the 742-molecule testset, much higher than that of pure force field method (FFBM, about 37%). On the other hand, MECBM achieved a more complete and efficient sampling of the conformational space because the average size of unique conformations ensemble per molecule is about 6 times larger than that of FFBM, while the time scale for conformational generation is nearly the same as FFBM. Furthermore, as a complementary comparison study between the methods with and without empirical biases, we also tested the performance of the three conformational generation methods in MacroModel in combination with different force fields. Compared with the methods in MacroModel, MECBM is more competitive in retrieving the bioactive conformations in light of accuracy but has much lower computational cost.</p> <p>Conclusions</p> <p>By incorporating different energy terms with several empirical criteria, the MECBM method can produce more reasonable conformational ensemble with high accuracy but approximately the same computational cost in comparison with FFBM method. Our analysis also reveals that the performance of conformational generation is irrelevant to the types of force field adopted in characterization of conformational accessibility. Moreover, post energy minimization is not necessary and may even undermine the diversity of conformational ensemble. All the results guide us to explore more empirical criteria like geometric restraints during the conformational process, which may improve the performance of conformational generation in combination with energetic accessibility, regardless of force field types adopted.</p

Constrained CMIP6 projections indicate less warming and a slower increase in water availability across Asia

Climate projections are essential for decision-making but contain non-negligible uncertainty. To reduce projection uncertainty over Asia, where half the world's population resides, we develop emergent constraint relationships between simulated temperature (1970-2014) and precipitation (2015-2100) growth rates using 27 CMIP6 models under four Shared Socioeconomic Pathways. Here we show that, with uncertainty successfully narrowed by 12.1-31.0%, constrained future precipitation growth rates are 0.39 ± 0.18 mm year-1 (29.36 mm °C-1, SSP126), 0.70 ± 0.22 mm year-1 (20.03 mm °C-1, SSP245), 1.10 ± 0.33 mm year-1 (17.96 mm °C-1, SSP370) and 1.42 ± 0.35 mm year-1 (17.28 mm °C-1, SSP585), indicating overestimates of 6.0-14.0% by the raw CMIP6 models. Accordingly, future temperature and total evaporation growth rates are also overestimated by 3.4-11.6% and -2.1-13.0%, respectively. The slower warming implies a lower snow cover loss rate by 10.5-40.2%. Overall, we find the projected increase in future water availability is overestimated by CMIP6 over Asia

Deletion of 1.8-kb mRNA of Marek's disease virus decreases its replication ability but not oncogenicity

<p>Abstract</p> <p>Background</p> <p>The 1.8-kb mRNA was reported as one of the oncogenesis-related genes of Marek's disease virus (MDV). In this study, the bacterial artificial chromosome (BAC) clone of a MDV field strain GX0101 was used as the platform to generate mutant MDV to examine the functional roles of 1.8-kb mRNA.</p> <p>Results</p> <p>Based on the BAC clone of GX0101, the 1.8-kb mRNA deletion mutant GX0101Δ(A+C) was constructed. The present experiments indicated that GX0101Δ(A+C) retained a low level of oncogenicity, and it showed a decreased replication capacity in vitro and in vivo when compared with its parent virus, GX0101. Further studies in vitro demonstrated that deletion of 1.8-kb mRNA significantly decreased the transcriptional activity of the bi-directional promoter between 1.8-kb mRNA and pp38 genes of MDV.</p> <p>Conclusion</p> <p>These results suggested that the 1.8-kb mRNA did not directly influence the oncogenesis but related to the replication ability of MDV.</p

The Application Value of the Central Lymph Node Metastasis Risk Assessment Model in Papillary Thyroid Microcarcinoma of Stage cN0: A Study of 828 Patients

BackgroundThe aim of this study is to build a risk assessment system for central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma (PTMC) of stage cN0 and to explore its application value in clinical practice.MethodsA total of 500 patients with PTMC who underwent thyroid operation from 2013 to 2015 in Ningbo First Hospital were selected as the model group. Independent risk factors related to CLNM in PTMC were analyzed and determined, and a risk assessment system for CLNM was preliminarily established. Furthermore, the clinicopathological data from 328 PTMC patients with the same conditions as the model group from 2016 to 2017 were further collected as the validation group to verify the diagnostic value of the risk assessment system.ResultsThe risk assessment system was based on the score rating (score ≤ 5 was classified as low risk, 6–8 was classified as medium risk, and ≥9 was classified as high-risk). The area under the receiver operating characteristic curve (ROC) was 0.687 (95% CI: 0.635–0.783). According to the risk assessment system, 328 PTMC patients in the validation group were scored. Among the low-risk group, the moderate-risk group, and the high-group, 96.8%, 58.1%, and 43.2% were the CLNM (-) patients, and 3.1%, 41.9%, and 65.8% were CLNM (+) patients, respectively. The area under ROC was 0.837 (95% CI: 0.778–0.869).ConclusionsThe risk assessment system in this study is of diagnostic value and can provide a theoretical foundation for intraoperative decision-making of prophylactic central neck dissection (pCND)

Phylogeography and demographic history of the cyprinid fish Barbodes semifasciolatus: implications for the history of landform changes in south mainland China, Hainan and Taiwan

Hainan Island and Taiwan Island are adjacent to the southern margin of mainland China and Vietnam. During glacial periods, global sea levels dropped, allowing that the land bridges connected the continental island and mainland, connecting rivers and providing dispersal opportunities that shaped the origin and diversification of freshwater fishes. Barbodes semifasciolatus is distributed in various water systems of Vietnam, Hainan, Taiwan, and southern mainland China and is restricted to the southern region of the Min River. Our study aimed to evaluate the genetic diversity and phylogeography of B. semifasciolatus using the mtDNA cyt b gene (1,141 bp). A total of 107 haplotypes were identified from 395 specimens in 23 populations, and high haplotype diversity (1.000) and low nucleotide diversity (0.0134) were detected. Mitochondrial phylogenetic analysis and haplotype network analyses revealed three major lineages according to geographical distribution. Lineage A was mainly distributed in Hainan Island, Vietnam and the southern region of the Pearl River in mainland China. Lineage B was distributed only in southeastern Hainan Island. Lineage C was distributed in the coastal rivers of mainland China and Taiwan. We suggest that the river in the Guangdong region is a colonization route in South Taiwan and that the populations distributed in the Pearl River region moved southward to Hainan Island and Vietnam based on the network and Bayesian binary MCMC (BBM) analysis. Our demographic history results indicated that the populations of B. semifasciolatus experienced a bottleneck event following a recent population expansion (DECINC model) supported by ABC analysis. We suggest that sea-level changes exerted pronounced effects on the demography of B. semifasciolatus on the continental island and in the mainland during the late Pleistocene glacial cycles