bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of multiphoton quantum states on silicon
Authors: Zhang Ming , Feng Lan-Tian , Zhou Zhi-Yuan , Chen Yang , Wu Hao , Li Ming , Gao Shi-Ming , Guo Guo-Ping , Guo Guang-Can , Dai Dao-Xin , Ren Xi-Feng 
Published: May 2019

AbstractMultiphoton quantum states play a critical role in emerging quantum technologies and greatly improve our fundamental understanding of the quantum world. Integrated photonics is well recognized as an attractive technology offering great promise for the generation of photonic quantum states with high-brightness, tunability, stability, and scalability. Herein, we demonstrate the generation of multiphoton quantum states using a single-silicon nanophotonic waveguide. The detected four-photon rate reaches 0.34 Hz even with a low-pump power of 600 μW. This multiphoton quantum state is also qualified with multiphoton quantum interference, as well as quantum state tomography. For the generated four-photon states, the quantum interference visibilities are greater than 95%, and the fidelity is 0.78 ± 0.02. Furthermore, such a multiphoton quantum source is fully compatible with the on-chip processes of quantum manipulation, as well as quantum detection, which is helpful for the realization of large-scale quantum photonic integrated circuits (QPICs) and shows great potential for research in the area of multiphoton quantum science.
nNOS/GSNOR interaction contributes to skeletal muscle differentiation and homeostasis
Authors: Montagna Costanza , Rizza Salvatore , Cirotti Claudia , Maiani Emiliano , Muscaritoli Maurizio , Musarò Antonio , Carrí Maria Teresa , Ferraro Elisabetta , Cecconi Francesco , Filomeni Giuseppe 
Published: May 2019

AbstractNeuronal nitric oxide synthase (nNOS) plays a crucial role in the maintenance of correct skeletal muscle function due, at least in part, to S-nitrosylation of specific protein targets. Similarly, we recently provided evidence for a muscular phenotype in mice lacking the denitrosylase S-nitrosoglutathione reductase (GSNOR). Here, we demonstrate that nNOS and GSNOR are concomitantly expressed during differentiation of C2C12. They colocalizes at the sarcolemma and co-immunoprecipitate in cells and in myofibers. We also provide evidence that GSNOR expression decreases in mouse models of muscular dystrophies and of muscle atrophy and wasting, i.e., aging and amyotrophic lateral sclerosis, suggesting a more general regulatory role of GSNOR in skeletal muscle homeostasis.
Angiotensin II inhibits apoptosis of mouse aortic smooth muscle cells through regulating the circNRG-1/miR-193b-5p/NRG-1 axis
Authors: Sun Yan , Zhang Suli , Yue Mingming , Li Yang , Bi Jing , Liu Huirong 
Published: May 2019

AbstractAngiotensin II (Ang II) is known to promote proliferation of vascular smooth muscle cells (VSMCs) in vascular remodeling, but whether it has an anti-apoptotic effect needs to be explored. Neuregulin-1 (NRG-1) as a member of the epidermal growth factor family was reported to suppress the proliferation of VSMCs by activating ErbB receptors, and therefore we hypothesized that there might be a cross talk between the anti-apoptotic effect of Ang II and the anti-proliferative effect of NRG-1 in VSMCs. The aim of the present study was to observe the expression and role of NRG-1 underlying the inhibitory effect of Ang II on apoptosis of mouse aortic smooth muscle cells (MASMCs). It was found that NRG-1 expression was down-regulated via the circNRG-1/miR-193b-5p-mediated post-transcriptional mechanism in response to Ang II. In addition, NRG-1 overexpression reversed the inhibitory effect of Ang II on apoptosis in MASMCs. Our data may provide a molecular basis for further understanding the mechanism of Ang II in suppressing the apoptosis of MASMCs by decreasing NRG-1 expression at circular RNA and micro RNA levels. The circNRG-1/miR-193b-5p/NRG-1 axis may prove to be a potential target for Ang II to inhibit the apoptosis of VSMCs and lead to vascular remodeling.
SIRT1 deacetylated and stabilized XRCC1 to promote chemoresistance in lung cancer
Authors: Yousafzai Neelum Aziz , Zhou Qiyin , Xu Wenxia , Shi Qiqi , Xu Jinye , Feng Lifeng , Chen Hui , Shin Vivian Yvonne , Jin Hongchuan , Wang Xian 
Published: May 2019

AbstractChemoresistance is one of the most important challenges in the clinical management of lung cancer. SIRT1 is a NAD dependent protein deacetylase and implicated in diverse cellular processes such as DNA damage repair, and cancer progression. SIRT1 is upregulated in chemoresistant lung cancer cells, genetic knockdown or chemical inhibition of SIRT1 reversed chemoresistance by enhancing DNA damage and apoptosis activation, accompanied with XRCC1 degradation. E3 ligase β-TrCP catalyzed the poly-ubiquitination of XRCC1 to promote its proteasome-dependent degradation. SIRT1 bound and deacetylated XRCC1 at lysine K260, K298 and K431, preventing it from β-TrCP-dependent ubiquitination. Mutations of these three lysine sites in XRCC1 abrogated the interaction with β-TrCP and prolonged the half-life of XRCC1 protein. Here, we describes SIRT1 confers chemoresistance to lung cancer cells by deacetylating and stabilizing XRCC1. Therefore, targeting SIRT1 might be a new strategy to manage the chemoresistance of lung cancer, and probably other cancers.
PRMT1 regulates the tumour-initiating properties of esophageal squamous cell carcinoma through histone H4 arginine methylation coupled with transcriptional activation
Authors: Zhao Yue , Lu Qijue , Li Chunguang , Wang Xinyu , Jiang Long , Huang Lei , Wang Chao , Chen Hezhong 
Published: May 2019

AbstractEsophageal squamous cell carcinoma (ESCC) is the most difficult subtype of esophageal cancer to treat due to a paucity of effective targeted therapy. ESCC is believed to arise from tumour initiating cells (TICs), which contribute to metastasis and chemoresistance. In this study, we found that Protein arginine methyltransferase 1(PRMT1) was highly expressed in ESCCs and associated with aberrant clinicopathological characteristics of ESCC patients. In ESCC specimens, the elevated expression of PRMT1 and OV6 was significantly associated with histologic grade, TNM stage and poor patient prognosis. Moreover, overexpression of PRMT1 was observed in esophageal TICs purified by magnetic sorting of adherent and spheroid ECA109/TE1 cells. The increased level of PRMT1 in TICs facilitated the expression of TIC markers, stem cell-like properties, resistance to chemotherapy, tumorigenicity and increased their percentages in ECSS samples. Conversely, knockdown of PRMT1 significantly diminished the self-renewal properties of ESCC. Moreover, we show that PRMT1 can catalyse histone H4R3 asymmetric dimethylation and promote transcription activation of down-stream genes. Further RNA-Seq transcriptome analysis reveals that overexpression of PRMT1 in ESCC cell lines activates Wnt/β-catenin and Notch signaling pathway. Together, our studies highlight that PRMT1 activates and maintains esophageal TICs by mediating transcription alteration through histone H4 arginine methylation.
ALK5 signaling pathway mediates neurogenesis and functional recovery after cerebral ischemia/reperfusion in rats via Gadd45b
Authors: Zhang Keming , Zhang Qinbin , Deng Jing , Li Jinfang , Li Jiani , Wen Lan , Ma Jingxi , Li Changqing 
Published: May 2019

AbstractTransforming growth factor β (TGF-β) serves critical functions in brain injury, especially in cerebral ischemia; however, apart from its neuroprotective effects, its role in regulating neurogenesis is unclear. TGF-β acts in different ways; the most important, canonical TGF-β activity involves TGF-β receptor I (TβRI) or the activin receptor-like kinase 5 (ALK5) signaling pathway. ALK5 signaling is a major determinant of adult neurogenesis. In our previous studies, growth arrest and DNA damage protein 45b (Gadd45b) mediated axonal plasticity after stroke. Here, we hypothesized that ALK5 signaling regulates neural plasticity and neurological function recovery after cerebral ischemia/reperfusion (I/R) via Gadd45b. First, ALK5 expression was significantly increased in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. Then, we knocked down or overexpressed ALK5 with lentivirus (LV) in vivo. ALK5 knockdown reduced axonal and dendritic plasticity, with a concomitant decrease in neurological function recovery. Conversely, ALK5 overexpression significantly increased neurogenesis as well as functional recovery. Furthermore, ALK5 mediated Gadd45b protein levels by regulating Smad2/3 phosphorylation. Finally, ALK5 coimmunoprecipitated with Gadd45b. Our results suggested that the ALK5 signaling pathway plays a critical role in mediating neural plasticity and neurological function recovery via Gadd45b after cerebral ischemia, representing a new potential target for cerebral I/R injury.
AXL degradation in combination with EGFR-TKI can delay and overcome acquired resistance in human non-small cell lung cancer cells
Authors: Kim Donghwa , Bach Duc-Hiep , Fan Yan-Hua , Luu Thi-Thu-Trang , Hong Ji-Young , Park Hyen Joo , Lee Sang Kook 
Published: May 2019

AbstractAcquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. AXL has been reported to mediate EGFR-TKIs. Recently, third generation EGFR-TKI osimertinib has been approved and yet its acquired resistance mechanism is not clearly understood. We found that AXL is involved in both gefitinib and osimertinib resistance using in vitro and in vivo model. In addition, AXL overexpression was correlated with extended protein degradation rate. We demonstrate targeting AXL degradation is an alternative route to restore EGFR-TKIs sensitivity. We confirmed that the combination effect of YD, an AXL degrader, and EGFR-TKIs can delay or overcome EGFR-TKIs-driven resistance in EGFR-mutant NSCLC cells, xenograft tumors, and patient-derived xenograft (PDX) models. Therefore, combination of EGFR-TKI and AXL degrader is a potentially effective treatment strategy for overcoming and delaying acquired resistance in NSCLC.
Mechanism-based tuning of insect 3,4-dihydroxyphenylacetaldehyde synthase for synthetic bioproduction of benzylisoquinoline alkaloids
Authors: Vavricka Christopher J. , Yoshida Takanobu , Kuriya Yuki , Takahashi Shunsuke , Ogawa Teppei , Ono Fumie , Agari Kazuko , Kiyota Hiromasa , Li Jianyong , Ishii Jun , Tsuge Kenji , Minami Hiromichi , Araki Michihiro , Hasunuma Tomohisa , Kondo Akihiko 
Published: May 2019

AbstractPrevious studies have utilized monoamine oxidase (MAO) and L-3,4-dihydroxyphenylalanine decarboxylase (DDC) for microbe-based production of tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) precursor to opioid analgesics. In the current study, a phylogenetically distinct Bombyx mori 3,4-dihydroxyphenylacetaldehyde synthase (DHPAAS) is identified to bypass MAO and DDC for direct production of 3,4-dihydroxyphenylacetaldehyde (DHPAA) from L-3,4-dihydroxyphenylalanine (L-DOPA). Structure-based enzyme engineering of DHPAAS results in bifunctional switching between aldehyde synthase and decarboxylase activities. Output of dopamine and DHPAA products is fine-tuned by engineered DHPAAS variants with Phe79Tyr, Tyr80Phe and Asn192His catalytic substitutions. Balance of dopamine and DHPAA products enables improved THP biosynthesis via a symmetrical pathway in Escherichia coli. Rationally engineered insect DHPAAS produces (R,S)-THP in a single enzyme system directly from L-DOPA both in vitro and in vivo, at higher yields than that of the wild-type enzyme. However, DHPAAS-mediated downstream BIA production requires further improvement.
Fluidal pyroclasts reveal the intensity of peralkaline rhyolite pumice cone eruptions
Authors: Clarke Ben , Calder Eliza S. , Dessalegn Firawalin , Fontijn Karen , Cortés Joaquín A. , Naylor Mark , Butler Ian , Hutchison William , Yirgu Gezahegn 
Published: May 2019

AbstractPeralkaline rhyolites are medium to low viscosity, volatile-rich magmas typically associated with rift zones and extensional settings. The dynamics of peralkaline rhyolite eruptions remain elusive with no direct observations recorded, significantly hindering the assessment of hazard and risk. Here we describe uniquely-preserved, fluidal-shaped pyroclasts found within pumice cone deposits at Aluto, a peralkaline rhyolite caldera in the Main Ethiopian Rift. We use a combination of field-observations, geochemistry, X-ray computed microtomography (XCT) and thermal-modelling to investigate how these pyroclasts are formed. We find that they deform during flight and, depending on size, quench prior to deposition or continue to inflate then quench in-situ. These findings reveal important characteristics of the eruptions that gave rise to them: that despite the relatively low viscosity of these magmas, and similarities to basaltic scoria-cone deposits, moderate to intense, unstable, eruption columns are developed; meaning that such eruptions can generate extensive tephra-fall and pyroclastic density currents.
Electrocardiogram generation with a bidirectional LSTM-CNN generative adversarial network
Authors: Zhu Fei , Ye Fei , Fu Yuchen , Liu Quan , Shen Bairong 
Published: May 2019

AbstractHeart disease is a malignant threat to human health. Electrocardiogram (ECG) tests are used to help diagnose heart disease by recording the heart’s activity. However, automated medical-aided diagnosis with computers usually requires a large volume of labeled clinical data without patients' privacy to train the model, which is an empirical problem that still needs to be solved. To address this problem, we propose a generative adversarial network (GAN), which is composed of a bidirectional long short-term memory(LSTM) and convolutional neural network(CNN), referred as BiLSTM-CNN,to generate synthetic ECG data that agree with existing clinical data so that the features of patients with heart disease can be retained. The model includes a generator and a discriminator, where the generator employs the two layers of the BiLSTM networks and the discriminator is based on convolutional neural networks. The 48 ECG records from individuals of the MIT-BIH database were used to train the model. We compared the performance of our model with two other generative models, the recurrent neural network autoencoder(RNN-AE) and the recurrent neural network variational autoencoder (RNN-VAE). The results showed that the loss function of our model converged to zero the fastest. We also evaluated the loss of the discriminator of GANs with different combinations of generator and discriminator. The results indicated that BiLSTM-CNN GAN could generate ECG data with high morphological similarity to real ECG recordings.
Native soil microorganisms hinder the soil enrichment with antibiotic resistance genes following manure applications
Authors: Pérez-Valera Eduardo , Kyselková Martina , Ahmed Engy , Sladecek Frantisek Xaver Jiri , Goberna Marta , Elhottová Dana 
Published: May 2019

AbstractBacterial genes responsible for resistance to antibiotic agents (ARG) are spread from livestock to soil through application of manure, threatening environmental and human health. We investigated the mechanisms of ARG dissemination and persistence to disentangle i) the influence of nutrients and microorganisms on the soil tetracycline (TET) resistome, and ii) the role of indigenous soil microbiota in preventing ARG spread. We analysed short-term (7 days) and persistent (84 days) effects of manure on the resistome of three antibiotic-free pasture soils. Four microcosm treatments were evaluated: control, mineral nutrient fertilization, and deposition of a layer of fresh manure onto soil or γ-irradiated soil. We quantified five TET-resistance genes, isolated 135 TET-resistant bacteria and sequenced both culturable TET-resistant and whole bacterial communities. Manure amendments, but not nutrient addition, increased the abundance of TET-r genes such as tet(Y). Such changes persisted with time, in contrast with the TET-resistant bacterial composition, which partially recovered after manure amendments. Manured γ-irradiated soils showed significantly lower nutrient content and higher TET-r gene abundance than non-irradiated soils, suggesting that native soil bacteria are essential for the fertilization effect of manure on soil as well as control the dissemination of potentially risky TET-r genes.
Drug-like Fragments Inhibit agr-Mediated Virulence Expression in Staphylococcus aureus
Authors: Bezar Ian F. , Mashruwala Ameya A. , Boyd Jeffrey M. , Stock Ann M. 
Published: May 2019

AbstractIn response to the increasingly problematic emergence of antibiotic resistance, novel strategies for combating pathogenic bacteria are being investigated. Targeting the agr quorum sensing system, which regulates expression of virulence in Staphylococcus aureus, is one potentially useful approach for combating drug-resistant pathogens that has not yet been fully explored. A previously published study of a fragment screen resulted in the identification of five compound fragments that interact with the DNA-binding domain of the response regulator AgrA from S. aureus. We have analyzed the ability of these compounds to affect agr-mediated virulence gene expression in cultured S. aureus cells. Three of the compounds demonstrated the ability to reduce agr-driven transcription at the P2 and P3 promoters of the agr operon and increase biofilm formation, and two of these compounds also showed the ability to reduce levels of secreted toxins. The finding that the compounds tested were able to reduce agr activity suggests that they could be useful tools for probing the effects of agr inhibition. Furthermore, the characteristics of compound fragments make them good starting materials for the development of compound libraries to iteratively improve the inhibitors.
Downregulation of thromboxane A2 and angiotensin II type 1 receptors associated with aging-related decrease in internal anal sphincter tone
Authors: Mohanty Ipsita , Singh Jagmohan , Rattan Satish 
Published: May 2019

AbstractAging-associated decrease in internal anal sphincter (IAS) tone (AADI) is a major contributor in the rectoanal incontinence (RI). To determine the pathogenesis of AADI, we investigated the effect of aging on GPCR activation and related downstream signaling. We particularly investigated two GPCRs that characterize IAS smooth muscle cells (SMCs): thromboxane A2 and angiotensin II type 1. Two groups of Fischer 344 rats (6-month-old [young group] and 26-month-old [old group]) were employed to determine the GPCR function by isometric contraction, the expressions of GPCRs, and their downstream regulatory signaling proteins (regulator of G-protein signaling 2, RGS2; GPCR Kinase 5, GRK5; and β-arrestin, Arrb2) using RT-PCR, qPCR, and western blot analyses. We used reversible biotinylation to monitor the GPCR trafficking using SMCs. Aging selectively attenuated thromboxane A2 and Ang II-induced IAS contraction. RT-PCR, qPCR, and WB data revealed a significant decrease in the expressions of the GPCRs and increase in the expression of RGS2, GRK5, and Arrb2. The increased GPCR internalization and decreased recycling under aging were validated by reversible biotinylation. We conclude that downregulation of GPCR, accompanied by upregulation of regulatory proteins, plays an important role in receptor desensitization and may be important underlying mechanisms of RI in certain aging patients.
Automated generation of Kochen-Specker sets
Authors: Pavičić Mladen , Waegell Mordecai , Megill Norman D. , Aravind P. K. 
Published: May 2019

AbstractQuantum contextuality turns out to be a necessary resource for universal quantum computation and also has applications in quantum communication. Thus it becomes important to generate contextual sets of arbitrary structure and complexity to enable a variety of implementations. In recent years, such generation has been done for contextual sets known as Kochen-Specker sets. Up to now, two approaches have been used for massive generation of non-isomorphic Kochen-Specker sets: exhaustive generation up to a given size and downward generation from master sets and their associated coordinatizations. Master sets were obtained earlier from serendipitous or intuitive connections with polytopes or Pauli operators, and more recently from arbitrary vector components using an algorithm that generates orthogonal vector groupings from them. However, both upward and downward generation face an inherent exponential complexity barrier. In contrast, in this paper we present methods and algorithms that we apply to downward generation that can overcome the exponential barrier in many cases of interest. These involve tailoring and manipulating Kochen-Specker master sets obtained from a small number of simple vector components, filtered by the features of the sets we aim to obtain. Some of the classes of Kochen-Specker sets we generate contain all previously known ones, and others are completely novel. We provide examples of both kinds in 4- and 6-dim Hilbert spaces. We also give a brief introduction for a wider audience and a novice reader.
Chemovirotherapeutic Treatment Using Camptothecin Enhances Oncolytic Measles Virus-Mediated Killing of Breast Cancer Cells
Authors: Tai Chen-Jei , Liu Ching-Hsuan , Pan Yu-Chi , Wong Shu Hui , Tai Cheng-Jeng , Richardson Christopher D. , Lin Liang-Tzung 
Published: May 2019

AbstractOncolytic virotherapy represents an emerging development in anticancer therapy. Although it has been tested against a variety of cancers, including breast cancer, the efficacy of oncolytic viral vectors delivered as a monotherapy is limited. Enhancing viral oncolytic therapies through combination treatment with anticancer agents is a feasible strategy. In this study, we considered a chemovirotherapeutic approach for treating breast adenocarcinoma using oncolytic measles virus (MV) and the chemotherapeutic agent camptothecin (CPT). Our results demonstrated that co-treatment of MV with CPT yielded enhanced cytotoxicity against breast cancer cells. Low dosage CPT combined with MV was also found to elicit the same therapeutic effect as high doses of CPT. At the lower dosage used, CPT did not inhibit the early stages of MV entry, nor reduce viral replication. Further studies revealed that co-treatment induced significantly enhanced apoptosis of the breast cancer cells compared to either MV or CPT alone. Overall, our findings demonstrate the potential value of MV plus CPT as a novel chemovirotherapeutic treatment against breast cancer and as a strategy to enhance MV oncolytic activity.
Variational principle for scale-free network motifs
Authors: Stegehuis Clara , Hofstad Remco van der , van Leeuwaarden Johan S. H. 
Published: May 2019

AbstractFor scale-free networks with degrees following a power law with an exponent τ ∈ (2, 3), the structures of motifs (small subgraphs) are not yet well understood. We introduce a method designed to identify the dominant structure of any given motif as the solution of an optimization problem. The unique optimizer describes the degrees of the vertices that together span the most likely motif, resulting in explicit asymptotic formulas for the motif count and its fluctuations. We then classify all motifs into two categories: motifs with small and large fluctuations.