407 research outputs found

    ‘Relax and Repair’ to restrain aging

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    The maintenance of genomic integrity requires the precise identification and repair of DNA damage. Since DNA is packaged and condensed into higher order chromatin, the events associated with DNA damage recognition and repair are orchestrated within the layers of chromatin. Very similar to transcription, during DNA repair, chromatin remodelling events and histone modifications act in concert to ‘open’ and relax chromatin structure so that repair proteins can gain access to DNA damage sites. One such histone mark critical for maintaining chromatin structure is acetylated lysine 16 of histone H4 (AcH4K16), a modification that can disrupt higher order chromatin organization and convert it into a more ‘relaxed’ configuration. We have recently shown that impaired H4K16 acetylation delays the accumulation of repair proteins to double strand break (DSB) sites which results in defective genome maintenance and accelerated aging in a laminopathy-based premature aging mouse model. These results support the idea that epigenetic factors may directly contribute to genomic instability and aging by regulating the efficiency of DSB repair. In this article, the interplay between epigenetic misregulation, defective DNA repair and aging is discussed

    Semi-Supervised Learning for Neural Machine Translation

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    While end-to-end neural machine translation (NMT) has made remarkable progress recently, NMT systems only rely on parallel corpora for parameter estimation. Since parallel corpora are usually limited in quantity, quality, and coverage, especially for low-resource languages, it is appealing to exploit monolingual corpora to improve NMT. We propose a semi-supervised approach for training NMT models on the concatenation of labeled (parallel corpora) and unlabeled (monolingual corpora) data. The central idea is to reconstruct the monolingual corpora using an autoencoder, in which the source-to-target and target-to-source translation models serve as the encoder and decoder, respectively. Our approach can not only exploit the monolingual corpora of the target language, but also of the source language. Experiments on the Chinese-English dataset show that our approach achieves significant improvements over state-of-the-art SMT and NMT systems.Comment: Corrected a typ

    Surgical treatment of spinal tenosynovial giant cell tumor: Experience from a single center and literature review

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    IntroductionSpinal tenosynovial giant cell tumor (TGCT) is a rare benign primary spinal tumor with aggressive behavior. The treatment strategy and prognosis of spinal TGCT remain unclear. This retrospective study aimed to evaluate the effectiveness of surgical treatment of spinal TGCT.MethodsWe enrolled 18 patients with spinal TGCT who underwent surgical treatment in our hospital between January 2002 and January 2021. Additionally, we reviewed 72 cases of spinal TGCT with surgical treatment reported in the previous literature. Therefore, a total of 90 cases of spinal TGCT were evaluated for their clinical characteristics, surgical details, radiotherapy, and prognosis.ResultsIn terms of the extent of resection, 73 cases (81.1%) underwent gross total resection (GTR), and 17 cases (18.9%) underwent subtotal resection (STR). Regarding the technique of GTR, 12 cases (16.7%) underwent en bloc resection, while 60 cases (83.3%) underwent piecemeal resection. During a median follow-up duration of 36 months (range: 3–528 months), 17.8% (16/90) cases experienced local recurrence/progression. The local recurrence/progression rate in cases that underwent GTR was 8.2% (6/73), which was significantly lower than that in cases with STR (58.8%, 10/17) (p<0.001). The local recurrence/progression rate of en bloc resection was 8.3% (1/12), and that of piecemeal resection was 8.3% (5/60). Twelve cases underwent perioperative adjuvant radiotherapy, and one (8.3%, 1/12) of them showed disease progression during follow-up. Six recurrent/progressive lesions were given radiotherapy and all of them remained stable in the subsequent follow-up. Eight recurrent/progressive lesions were only treated with re-operation without radiotherapy, and half of them (50.0%, 4/8) demonstrated repeated recurrence/progression in the subsequent follow-up.ConclusionSurgical treatment could be effective for spinal TGCT cases, and GTR is the preferred surgical strategy. Piecemeal resection may be appropriate for spinal TGCT cases with an acceptable local recurrence/progression rate. Perioperative adjuvant radiotherapy may reduce the risk of postoperative local recurrence/progression, and radiotherapy plays an important role in the treatment of recurrent/unresectable spinal TGCT lesions

    Robust Optimization of Fourth Party Logistics Network Design under Disruptions

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    The Fourth Party Logistics (4PL) network faces disruptions of various sorts under the dynamic and complex environment. In order to explore the robustness of the network, the 4PL network design with consideration of random disruptions is studied. The purpose of the research is to construct a 4PL network that can provide satisfactory service to customers at a lower cost when disruptions strike. Based on the definition of β-robustness, a robust optimization model of 4PL network design under disruptions is established. Based on the NP-hard characteristic of the problem, the artificial fish swarm algorithm (AFSA) and the genetic algorithm (GA) are developed. The effectiveness of the algorithms is tested and compared by simulation examples. By comparing the optimal solutions of the 4PL network for different robustness level, it is indicated that the robust optimization model can evade the market risks effectively and save the cost in the maximum limit when it is applied to 4PL network design

    Stable isotope probing reveals compositional and functional shifts in active denitrifying communities along the soil profile in an intensive agricultural area

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    Denitrifying microbial communities in the vadose zone play an essential role in eliminating the nitrate leached from agricultural practices. This nitrate could otherwise contaminate groundwater and threaten public health. Here, we utilized stable isotope probing combined with amplicon sequencing and functional gene quantification to inspect the composition and function of heterotrophic denitrifying microorganisms along a 9-m soil profile in an intensive agricultural area. Dramatic differences in the composition of the active denitrifiers were uncovered between the surface soil and deep layers of the vadose zone. The main denitrifying bacterial taxa identified from 13C-DNA fractions were Pseudomonadaceae (Pseudomonas), Rhodocyclaceae (Azoarcus), and Burkholderiaceae in the surface soil (0–0.2 m), and were Pseudomonadaceae (Pseudomonas), Burkholderiaceae, Bacillaceae (Bacillus), and Paenibacillaceae (Ammoniphilus) in the deep layers (0.5–9.0 m). Analysis of the functional genes (nirS, nirK, and nosZ) in isotope-labeled DNA revealed an upward nos/nir ratio with increasing soil depth, which may account for the higher nitrous oxide emission potential in the surface soil, as compared to the deeper sand-rich, low organic carbon layers. This study improves our understanding of active denitrifying microbes in the vadose zone and helps in developing techniques to reduce nitrate pollution in groundwater
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