•A self-learning GA (SLGA) which combines both SARSA and Q-learning with GA is first proposed to solve FJSP.•The combined model of SLGA is constructed according to the features of GA and RL.•SARSA ...algorithm and Q-learning algorithm of RL are combined, which constitute the main part of learning module in SLGA.•The components of RL are designed, including the state of GA environment, action of parameters adjustment, and reward method.•The mixedstrategy of SARSA algorithm and Q-learning algorithm improve the efficiency of SLGA for FJSP.
As an important branch of production scheduling, flexible job-shop scheduling problem (FJSP) is difficult to solve and is proven to be NP-hard. Many intelligent algorithms have been proposed to solve FJSP, but their key parameters cannot be dynamically adjusted effectively during the calculation process, which causes the solution efficiency and quality not being able to meet the production requirements. Therefore, a self-learning genetic algorithm (SLGA) is proposed in this paper, in which genetic algorithm (GA) is adopted as the basic optimization method and its key parameters are intelligently adjusted based on reinforcement learning (RL). Firstly, the self-learning model is analyzed and constructed in SLGA, SARSA algorithm and Q-Learning algorithm are applied as the learning methods at initial and later stages of optimization, respectively, and the conversion condition is designed. Secondly, the state determination method and reward method are designed for RL in GA environment. Finally, the learning effect and performance of SLGA in solving FJSP are compared with other algorithms using two groups of benchmark data instances with different scales. Experiment results show that the proposed SLGA significantly outperforms its competitors in solving FJSP.
Ischemic stroke can induce changes in mitochondrial morphology and function. As a regulatory gene in mitochondria, optic atrophy 1 (OPA1) plays a pivotal role in the regulation of mitochondrial ...dynamics and other related functions. However, its roles in cerebral ischemia-related conditions are barely understood.
Cultured rat primary cortical neurons were respectively transfected with OPA1-v1ΔS1-encoding and OPA1-v1-encoding lentivirus before exposure to 2-h oxygen-glucose deprivation (OGD) and subsequent reoxygenation (OGD/R). Adult male SD rats received an intracranial injection of AAV-OPA1-v1ΔS1 and were subjected to 90 min of transient middle cerebral artery occlusion (tMCAO) followed by reperfusion. OPA1 expression and function were detected by in vitro and in vivo assays.
OPA1 was excessively cleaved after cerebral ischemia/reperfusion injury, both in vitro and in vivo. Under OGD/R condition, compared with that of the LV-OPA1-v1-treated group, the expression of OPA1-v1ΔS1 efficiently restored L-OPA1 level and alleviated neuronal death and mitochondrial morphological damage. Meanwhile, the expression of OPA1-v1ΔS1 markedly improved cerebral ischemia/reperfusion-induced motor function damage, attenuated brain infarct volume, neuronal apoptosis, mitochondrial bioenergetics deficits, oxidative stress, and restored the morphology of mitochondrial cristae and mitochondrial length. It also preserved the mitochondrial integrity and reinforced the mtDNA content and expression of mitochondrial biogenesis factors in ischemic rats.
Our results demonstrate that the stabilization of L-OPA1 protects ischemic brains by reducing neuronal apoptosis and preserving mitochondrial function, suggesting its significance as a promising therapeutic target for stroke prevention and treatment.
We developed PolyA-seq, a strand-specific and quantitative method for high-throughput sequencing of 3' ends of polyadenylated transcripts, and used it to globally map polyadenylation (polyA) sites in ...24 matched tissues in human, rhesus, dog, mouse, and rat. We show that PolyA-seq is as accurate as existing RNA sequencing (RNA-seq) approaches for digital gene expression (DGE), enabling simultaneous mapping of polyA sites and quantitative measurement of their usage. In human, we confirmed 158,533 known sites and discovered 280,857 novel sites (FDR < 2.5%). On average 10% of novel human sites were also detected in matched tissues in other species. Most novel sites represent uncharacterized alternative polyA events and extensions of known transcripts in human and mouse, but primarily delineate novel transcripts in the other three species. A total of 69.1% of known human genes that we detected have multiple polyA sites in their 3'UTRs, with 49.3% having three or more. We also detected polyadenylation of noncoding and antisense transcripts, including constitutive and tissue-specific primary microRNAs. The canonical polyA signal was strongly enriched and positionally conserved in all species. In general, usage of polyA sites is more similar within the same tissues across different species than within a species. These quantitative maps of polyA usage in evolutionarily and functionally related samples constitute a resource for understanding the regulatory mechanisms underlying alternative polyadenylation.
Based on big data and cloud computing technology, the development process of this system includes hardware cluster deployment of the delivery system, optimization of website delivery strategy, and ...development of the delivery management background system. The main functions in the following aspects are realized: first, we built the website back-end delivery subsystem and data collection and analysis subsystem to realize the control of website delivery and data collection; second, we designed and developed a process management subsystem for booking, management, and delivery of website resources and developed the contract management and order management subsystems to realize the accurate placement of user portraits on the website; then, the placement data monitoring and effect feedback subsystems, and the data inventory subsystem of the website system were designed and developed. Finally, based on the research of Android and based on the Eclipse platform, this article has completed the construction of the Android 4.0.3 version environment, successfully used the Java development language to develop a website information intelligent analysis and navigation system, and analyzed the various functional modules of the entire system. Experimental results show that the system not only realizes ordinary route and site query functions but also combines map API, integrates big data and cloud computing technology, and realizes congestion avoidance query, time optimal query, population heat map, and real-time viewing. The nearby use of this software’s personnel density distribution and other functions provides great convenience for personal travel, which can facilitate the real-time planning of travel plans, and has great practical and practical significance. Through the different levels of testing of various subsystems, the website delivery system meets the functional and nonfunctional requirements proposed by the network and on this basis realizes the use of group wisdom based on Pearson correlation coefficient, Cosine similarity, and Tanimoto coefficient for collaborative filtering website recommendation algorithm.
The Passive containment Air-cooling System (PAS) can effectively remove the decay heat of the modular small nuclear reactor after an accident. The details of natural convection around the dome, which ...is a key part of PAS, were investigated numerically in the present study. The thermal dynamics around the dome were studied through the temperature, pressure and velocity contours and the streamlines. Additionally, the formation of the buoyant plume at the top of the dome was investigated. The results show that with the increase of Ra, the lift-off point moves toward the bottom of the dome, and the eddy under the buoyant plume grows larger gradually, which enhances the heat transfer. And the heat transfer along the dome surface with different truncation angles was investigated. As the angle increases, the heat transfer coefficient becomes stronger as well. Consequently, a newly developed heat transfer correlation considering the influence of truncation angle for the dome is proposed based on the simulated results. This study could provide a better understanding of natural convection around the dome of PAS and the proposed correlation could also offer more predictive value in the improvement of nuclear safety.
To survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent ...normal tissues. We found that HBV integration is observed more frequently in the tumors (86.4%) than in adjacent liver tissues (30.7%). Copy-number variations (CNVs) were significantly increased at HBV breakpoint locations where chromosomal instability was likely induced. Approximately 40% of HBV breakpoints within the HBV genome were located within a 1,800-bp region where the viral enhancer, X gene and core gene are located. We also identified recurrent HBV integration events (in ≥ 4 HCCs) that were validated by RNA sequencing (RNA-seq) and Sanger sequencing at the known and putative cancer-related TERT, MLL4 and CCNE1 genes, which showed upregulated gene expression in tumor versus normal tissue. We also report evidence that suggests that the number of HBV integrations is associated with patient survival.
Gastric cancer (GC) is the second most common cause of cancer-related deaths. It is known to be a heterogeneous disease with several molecular and histological subtypes. Here we perform whole-genome ...sequencing of 49 GCs with diffuse (N=31) and intestinal (N=18) histological subtypes and identify three mutational signatures, impacting TpT, CpG and TpCpA/T nucleotides. The diffuse-type GCs show significantly lower clonality and smaller numbers of somatic and structural variants compared with intestinal subtype. We further divide the diffuse subtype into one with infrequent genetic changes/low clonality and another with relatively higher clonality and mutations impacting TpT dinucleotide. Notably, we discover frequent and exclusive mutations in Ephrins and SLIT/ROBO signalling pathway genes. Overall, this study delivers new insights into the mutational heterogeneity underlying distinct histologic subtypes of GC that could have important implications for future research in the diagnosis and treatment of GC.
As a classic immunoregulatory and anti-inflammatory cytokine, interleukin-10 (IL-10) provides neuroprotection in cerebral ischemia in vivo or oxygen-glucose deprivation (OGD)-induced injury in vitro. ...However, it remains blurred whether IL-10 promotes neurite outgrowth and synapse formation in cultured primary cortical neurons after OGD injury. In order to evaluate its effect on neuronal apoptosis, neurite outgrowth and synapse formation, we administered IL-10 or IL-10 neutralizing antibody (IL-10NA) to cultured rat primary cortical neurons after OGD injury. We found that IL-10 treatment activated the Janus kinase 1 (JAK1)/signal transducers and activators of transcription 3 (STAT3) signaling pathway. Moreover, IL-10 attenuated OGD-induced neuronal apoptosis by down-regulating the Bax expression and up-regulating the Bcl-2 expression, facilitated neurite outgrowth by increasing the expression of Netrin-1, and promoted synapse formation in cultured primary cortical neurons after OGD injury. These effects were partly abolished by JAK1 inhibitor GLPG0634. Contrarily, IL-10NA produced opposite effects on the cultured cortical neurons after OGD injury. Taken together, our findings suggest that IL-10 not only attenuates neuronal apoptosis, but also promotes neurite outgrowth and synapse formation via the JAK1/STAT3 signaling pathway in cultured primary cortical neurons after OGD injury.
Genes that participate in the degradation or isolation of glyphosate in plants are promising, for they endow crops with herbicide tolerance with a low glyphosate residue. Recently, the aldo-keto ...reductase (AKR4) gene in
(
) was identified as a naturally evolved glyphosate-metabolism enzyme. Here, we compared the glyphosate-degradation ability of theAKR4 proteins from maize, soybean and rice, which belong to a clade containing EcAKR4 in the phylogenetic tree, by incubation of glyphosate with AKR proteins both in vivo and in vitro. The results indicated that, except for OsALR1, the other proteins were characterized as glyphosate-metabolism enzymes, with ZmAKR4 ranked the highest activity, and OsAKR4-1 and OsAKR4-2 exhibiting the highest activity among the AKR4 family in rice. Moreover, OsAKR4-1 was confirmed to endow glyphosate-tolerance at the plant level. Our study provides information on the mechanism underlying the glyphosate-degradation ability of AKR proteins in crops, which enables the development of glyphosate-resistant crops with a low glyphosate residue, mediated by AKRs.
Hepatocellular carcinoma (HCC) is an aggressive and deadly cancer. The molecular pathogenesis of the disease remains poorly understood. To better understand HCC biology and explore potential ...biomarkers and therapeutic targets, we investigated the whole transcriptome of HCC. Considering the genetic heterogeneity of HCC, four datasets from four studies consisting of 15 pairs of HCC and adjacent normal samples were analyzed. We observed that the number of lncRNAs expressed in each HCC sample was consistently greater than the adjacent normal sample. Moreover, 15 lncRNAs were identified expressed in five to seven HCC tissues but were not detected in any adjacent normal tissue. Differential expression analysis detected 35 up- and 80 down-regulated lncRNAs in HCC samples compared with adjacent normal samples. In addition, five differentially expressed lncRNAs were predicted to play a role in oxidation and reduction process. With regard to splicing alterations, we identified nine highly recurrent differential splicing events belonging to eight genes
USO1
,
RPS24
,
CCDC50
,
THNSL2
,
NUMB
,
FN1
(two events),
SLC39A14
and
NR1I3
. Of them, splicing alterations of
SLC39A14
and
NR1I3
were reported for the association with HCC for the first time. The splicing dysregulation in HCC may be influenced by three splicing factors
ESRP2
,
CELF2
and
SRSF5
which were significantly down-regulated in HCC samples. This study revealed uncharacterized aspects of HCC transcriptome and identified important lncRNAs and splicing isoforms with the potential to serve as biomarkers and therapeutic targets for the disease.
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