bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causative role of PDLIM2 epigenetic repression in lung cancer and therapeutic resistance
Authors: Sun Fan , Li Liwen , Yan Pengrong , Zhou Jingjiao , Shapiro Steven D. , Xiao Gutian , Qu Zhaoxia 
Published: November 2019

AbstractMost cancers are resistant to anti-PD-1/PD-L1 and chemotherapy. Herein we identify PDLIM2 as a tumor suppressor particularly important for lung cancer therapeutic responses. While PDLIM2 is epigenetically repressed in human lung cancer, associating with therapeutic resistance and poor prognosis, its global or lung epithelial-specific deletion in mice causes increased lung cancer development, chemoresistance, and complete resistance to anti-PD-1 and epigenetic drugs. PDLIM2 epigenetic restoration or ectopic expression shows antitumor activity, and synergizes with anti-PD-1, notably, with chemotherapy for complete remission of most lung cancers. Mechanistically, through repressing NF-κB/RelA and STAT3, PDLIM2 increases expression of genes involved in antigen presentation and T-cell activation while repressing multidrug resistance genes and cancer-related genes, thereby rendering cancer cells vulnerable to immune attacks and therapies. We identify PDLIM2-independent PD-L1 induction by chemotherapeutic and epigenetic drugs as another mechanism for their synergy with anti-PD-1. These findings establish a rationale to use combination therapies for cancer treatment.
Synthesizing multi-phonon quantum superposition states using flux-mediated three-body interactions with superconducting qubits
Authors: Kounalakis Marios , Blanter Yaroslav M. , Steele Gary A. 
Published: November 2019

AbstractMassive mechanical resonators operating at the quantum scale can enable a large variety of applications in quantum technologies as well as fundamental tests of quantum theory. Of crucial importance in that direction is both their integrability into state-of-the-art quantum platforms as well as the ability to prepare them in generic quantum states using well-controlled high-fidelity operations. Here, we propose a scheme for controlling a radio-frequency mechanical resonator at the quantum scale using two superconducting transmon qubits that can be integrated on the same chip. Specifically, we consider two qubits coupled via a capacitor in parallel to a superconducting quantum interference device (SQUID), which has a suspended mechanical beam embedded in one of its arms. Following a theoretical analysis of the quantum system, we find that this configuration, in combination with an in-plane magnetic field, can give rise to a tuneable three-body interaction in the single-photon strong-coupling regime, while enabling suppression of the stray qubit-qubit coupling. Using state-of-the-art parameters and qubit operations at single-excitation levels, we numerically demonstrate the possibility of ground-state cooling as well as high-fidelity preparation of mechanical quantum states and qubit-phonon entanglement, i.e. states having negative Wigner functions and obeying non-classical correlations. Our work significantly extends the quantum control toolbox of radio-frequency mechanical resonators and may serve as a promising architecture for integrating such mechanical elements with transmon-based quantum processors.
Cambridge quantum network
Authors: Dynes J. F. , Wonfor A. , Tam W. W. -S. , Sharpe A. W. , Takahashi R. , Lucamarini M. , Plews A. , Yuan Z. L. , Dixon A. R. , Cho J. , Tanizawa Y. , Elbers J. -P. , Greißer H. , White I. H. , Penty R. V. , Shields A. J. 
Published: November 2019

AbstractFuture-proofing current fibre networks with quantum key distribution (QKD) is an attractive approach to combat the ever growing breaches of data theft. To succeed, this approach must offer broadband transport of quantum keys, efficient quantum key delivery and seamless user interaction, all within the existing fibre network. However, quantum networks to date either require dark fibres and/or offer bit rates inadequate for serving a large number of users. Here we report a city wide high-speed metropolitan QKD network—the Cambridge quantum network—operating on fibres already populated with high-bandwidth data traffic. We implement a robust key delivery layer to demonstrate essential network operation, as well as enabling encryption of 100 Gigabit per second (Gbps) simultaneous data traffic with rapidly refreshed quantum keys. Network resilience against link disruption is supported by high-QKD link rates and network link redundancy. We reveal that such a metropolitan network can support tens of thousands of users with key rates in excess of 1 kilobit per second (kbps) per user. Our result hence demonstrates a clear path for implementing quantum security in metropolitan fibre networks.
Prediction Model of Organic Molecular Absorption Energies based on Deep Learning trained by Chaos-enhanced Accelerated Evolutionary algorithm
Authors: Li Mengshan , Lian Suyun , Wang Fan , Zhou Yanying , Chen Bingsheng , Guan Lixin , Wu Yan 
Published: November 2019

AbstractAs an important physical property of molecules, absorption energy can characterize the electronic property and structural information of molecules. Moreover, the accurate calculation of molecular absorption energies is highly valuable. Present linear and nonlinear methods hold low calculation accuracies due to great errors, especially irregular complicated molecular systems for structures. Thus, developing a prediction model for molecular absorption energies with enhanced accuracy, efficiency, and stability is highly beneficial. By combining deep learning and intelligence algorithms, we propose a prediction model based on the chaos-enhanced accelerated particle swarm optimization algorithm and deep artificial neural network (CAPSO BP DNN) that possesses a seven-layer 8-4-4-4-4-4-1 structure. Eight parameters related to molecular absorption energies are selected as inputs, such as a theoretical calculating value Ec of absorption energy (B3LYP/STO-3G), molecular electron number Ne, oscillator strength Os, number of double bonds Ndb, total number of atoms Na, number of hydrogen atoms Nh, number of carbon atoms Nc, and number of nitrogen atoms NN; and one parameter representing the molecular absorption energy is regarded as the output. A prediction experiment on organic molecular absorption energies indicates that CAPSO BP DNN exhibits a favourable predictive effect, accuracy, and correlation. The tested absolute average relative error, predicted root-mean-square error, and square correlation coefficient are 0.033, 0.0153, and 0.9957, respectively. Relative to other prediction models, the CAPSO BP DNN model exhibits a good comprehensive prediction performance and can provide references for other materials, chemistry and physics fields, such as nonlinear prediction of chemical and physical properties, QSAR/QAPR and chemical information modelling, etc.
The Role of Wettability on the Response of a Quartz Crystal Microbalance Loaded with a Sessile Droplet
Authors: Murray Brandon , Narayanan Shankar 
Published: November 2019

AbstractIn this work, the interaction between a sessile droplet’s contact angle and a quartz crystal microbalance (QCM) is elucidated. We differentiate the QCM’s frequency response to changes in the droplet contact area from variations in the dynamic contact angle. This is done by developing a computational model that couples the electrical and mechanical analysis of the quartz substrate with the visco-acoustic behavior of the sessile droplet. From our analysis, we conclude that changes in the contact angle have an effect on the frequency response of the QCM when the droplet height is on the order of the viscous decay length or smaller. On the other hand, changes in the interfacial contact area of the sessile droplets have a significant impact on the frequency response of the QCM regardless of the droplet size.
A Multi-Phasic Perspective of the Intact Permeability of the Heterogeneous Argillaceous Cobourg Limestone
Authors: Selvadurai A. P. S. 
Published: November 2019

AbstractThe Cobourg limestone is a heterogeneous argillaceous rock consisting of lighter nodular regions of calcite and dolomite, interspersed with darker regions composed of calcite, dolomite, quartz and a clay fraction. The intact permeability of the Cobourg limestone is estimated to be in the range of K ∈ (10−23, 10−19) m2. This paper discusses the factors influencing the measurement of the intact permeability of the Cobourg limestone and presents an upscaling approach for estimating this parameter. The procedure first involves the dissection of a cuboidal sample of the rock measuring, 80 mm × 120 mm × 300 mm, into ten 8 mm-thick slabs. Digital imaging and mapping of the larger surfaces of these sections are used to create, from both surface image extrusion and surface image interpolation techniques, the fabric within the dissected regions. The estimated permeabilities of the lighter and darker regions are used in the computational models of the computer-generated fabric to estimate the effective permeability of the rock. These results are complemented by estimates derived from mathematical theories for estimating permeabilities of multiphasic composites.
The Use of Motion Analysis as Particle Biomarkers in Lensless Optofluidic Projection Imaging for Point of Care Urine Analysis
Authors: Kun Jessica , Smieja Marek , Xiong Bo , Soleymani Leyla , Fang Qiyin 
Published: November 2019

AbstractUrine testing is an essential clinical diagnostic tool. The presence of urine sediments, typically analyzed through microscopic urinalysis or cell culture, can be indicative of many diseases, including bacterial, parasitic, and yeast infections, as well as more serious conditions like bladder cancer. Current urine analysis diagnostic methods are usually centralized and limited by high cost, inconvenience, and poor sensitivity. Here, we developed a lensless projection imaging optofluidic platform with motion-based particle analysis to rapidly detect urinary constituents without the need for concentration or amplification through culture. A removable microfluidics channel ensures that urine samples do not cross contaminate and the lens-free projection video is captured and processed by a low-cost integrated microcomputer. A motion tracking and analysis algorithm is developed to identify and track moving objects in the flow. Their motion characteristics are used as biomarkers to detect different urine species in near real-time. The results show that this technology is capable of detection of red and white blood cells, Trichomonas vaginalis, crystals, casts, yeast and bacteria. This cost-effective device has the potential to be implemented for timely, point-of-care detection of a wide range of disorders in hospitals, clinics, long-term care homes, and in resource-limited regions.
Spontaneous Yawning and its Potential Functions in South American Sea Lions (Otaria flavescens)
Authors: Palagi Elisabetta , Guillén-Salazar Federico , Llamazares-Martín Clara 
Published: November 2019

AbstractSpontaneous yawning is a widespread behaviour in vertebrates. However, data on marine mammals are scarce. In this study, we tested some hypotheses on the functions of yawning in a captive group of South American sea lions (Otaria flavescens). According to the Dimorphism Hypothesis, species showing low levels of sexual dimorphism in canine size do not show sex differences in yawning distribution; this was supported by our findings, since yawning did not differ between the sexes. Yawning was more frequently performed during resting/sleeping contexts, thus supporting the Drowsiness Hypothesis. Yawning and self-scratching are considered reliable indicators of short-term anxiety in sea lions, since they immediately increased after conflicts both in aggressors and victims (Social Distress Hypothesis supported). In the long-term, yawning was not correlated with individuals’ dominance status, thus showing that anxiety is similarly experienced by dominants and subordinates. The last two findings can be explained by the social competition of this species, that involves individuals independently from their sex, age or ranking status. Therefore, the exposure to frequent stressful events can induce similar levels of anxiety in all the subjects (Resource Inequity Hypothesis supported). In conclusion, spontaneous yawning in sea lions seems to share similar functions with other social mammals, suggesting that this behaviour is a possible plesiomorphic trait.
Induction of HLA-A2 restricted CD8 T cell responses against ApoB100 peptides does not affect atherosclerosis in a humanized mouse model
Authors: Schaftenaar Frank H. , Amersfoort Jacob , Douna Hidde , Kröner Mara J. , Foks Amanda C. , Bot Ilze , Slütter Bram A. , van Puijvelde Gijs H. M. , Drijfhout Jan W. , Kuiper Johan 
Published: November 2019

AbstractCardiovascular diseases form the most common cause of death worldwide, with atherosclerosis as main etiology. Atherosclerosis is marked by cholesterol rich lipoprotein deposition in the artery wall, evoking a pathogenic immune response. Characteristic for the disease is the pathogenic accumulation of macrophages in the atherosclerotic lesion, which become foam cells after ingestion of large quantities of lipoproteins. We hypothesized that, by inducing a CD8 T cell response towards lipoprotein derived apolipoprotein-B100 (ApoB100), lesional macrophages, that are likely to cross-present lipoprotein constituents, can specifically be eliminated. Based onin silicomodels for protein processing and MHC-I binding, 6 putative CD8 T cell epitopes derived from ApoB100 were synthesized. HLA-A2 binding was confirmed for all peptides by T2 cell binding assays and recall responses after vaccination with the peptides proved that 5 of 6 peptides could induce CD8 T cell responses. Induction of ApoB100 specific CD8 T cells did not impact plaque size and cellular composition in HLA-A2 and human ApoB100 transgenic LDLr−/−mice. No recall response could be detected in cultures of cells isolated from the aortic arch, which were observed in cell cultures of splenocytes and mesenteric lymph nodes, suggesting that the atherosclerotic environment impairs CD8 T cell activation.
Genetic disorder prenatal diagnosis and pregnancy termination practices among high consanguinity population, Saudi Arabia
Authors: AbdulAzeez Sayed , Al Qahtani Nourah H. , Almandil Noor B. , Al-Amodi Amani M. , Aldakeel Sumayh A. , Ghanem Neda Z. , Alkuroud Deem N. , AlTurki Ameen , AlQattan Quds Abdulhakeem , Alghamdi Abdulrahman , Alhur Norah Fahad , Al Taifi Hatoon Ahmed , Aljofi Halah Egal , Jermy B. Rabindran , Raman Vinoth , Giambona Antonino , Maggio Aurelio , Borgio J. Francis 
Published: November 2019

AbstractThe prevalence of consanguineous marriage and genetic disorders are high in Saudi Arabia. There were records on the practices of Saudis toward prenatal diagnosis (PND) and termination of pregnancy (TOP), however the sample sizes are small. This study has targeted the Saudi Arabian community and family history of genetic disorders to determine the practices toward PND and TOP. The cross-sectional survey was conducted among Saudis (n = 2761) to determine their practices toward reproductive-decision making. Regression analysis was conducted to identify the association of the limiting factors, relative merits and family history on the outcomes. Total of 2507 participants returned completed questionnaire. The practice towards PND (68%) were more favorable than TOP (33%). PND was found to be a good opportunity for early diagnosis and gives parent’s choice. Education, history with affected baby, prior knowledge and religious belief were significant deciding factors of PND and TOP. Down syndrome (n = 161) and sickle cell anemia (n = 152) were commonly available genetic disorder among participant’s family. Respondents with autistic cases in their family have higher acceptance rate for TOP. Non-consanguineous are more willing to consider TOP than consanguineous. Participants with abnormal fetus, aged of > 36 years, married and educated Saudis were more likely consider TOP. Though, religion is the most influencing factor for not accepting TOP, comparatively willingness to PND and TOP have increased recently. Awareness campaigns about PND and TOP may increase the chances of accepting prenatal genetic diagnosis.
Neurophysiological Correlates of Concussion: Deep Learning for Clinical Assessment
Authors: Boshra Rober , Ruiter Kyle I. , DeMatteo Carol , Reilly James P. , Connolly John F. 
Published: November 2019

AbstractConcussion has been shown to leave the afflicted with significant cognitive and neurobehavioural deficits. The persistence of these deficits and their link to neurophysiological indices of cognition, as measured by event-related potentials (ERP) using electroencephalography (EEG), remains restricted to population level analyses that limit their utility in the clinical setting. In the present paper, a convolutional neural network is extended to capitalize on characteristics specific to EEG/ERP data in order to assess for post-concussive effects. An aggregated measure of single-trial performance was able to classify accurately (85%) between 26 acutely to post-acutely concussed participants and 28 healthy controls in a stratified 10-fold cross-validation design. Additionally, the model was evaluated in a longitudinal subsample of the concussed group to indicate a dissociation between the progression of EEG/ERP and that of self-reported inventories. Concordant with a number of previous studies, symptomatology was found to be uncorrelated to EEG/ERP results as assessed with the proposed models. Our results form a first-step towards the clinical integration of neurophysiological results in concussion management and motivate a multi-site validation study for a concussion assessment tool in acute and post-acute cases.
The MUC5B mucin polymer is dominated by repeating structural motifs and its topology is regulated by calcium and pH
Authors: Hughes Gareth W. , Ridley Caroline , Collins Richard , Roseman Alan , Ford Robert , Thornton David J. 
Published: November 2019

AbstractThe polymeric mucin MUC5B provides the structural and functional framework of respiratory mucus, conferring both viscoelastic and antimicrobial properties onto this vital protective barrier. Whilst it is established that MUC5B forms disulfide-linked linear polymers, how this relates to their packaging in secretory granules, and their molecular form in mucus remain to be fully elucidated. Moreover, the role of the central heavily O-glycosylated mucin domains in MUC5B conformation is incompletely described. Here we have completed a detailed structural analysis on native MUC5B polymers purified from saliva and subsequently investigated how MUC5B conformation is affected by changes in calcium concentration and pH, factors important for mucin intragranular packaging and post-secretory expansion. The results identify that MUC5B has a beaded structure repeating along the polymer axis and suggest that these repeating motifs arise from distinct glycosylation patterns. Moreover, we demonstrate that the conformation of these highly entangled linear polymers is sensitive to calcium concentration and changes in pH. In the presence of calcium (Ca2+, 10 mM) at pH 5.0, MUC5B adopted a compact conformation which was lost either upon removal of calcium with EGTA, or by increasing the pH to 7.4. These results suggest a pathway of mucin collapse to enable intracellular packaging and mechanisms driving mucin expansion following secretion. They also point to the importance of the tight control of calcium and pH during different stages of mucin biosynthesis and secretion, and in the generation of correct mucus barrier properties.
Activation of heme oxygenase-1 by Ginkgo biloba extract differentially modulates endothelial and smooth muscle-like progenitor cells for vascular repair
Authors: Wu Tao-Cheng , Chen Jia-Shiong , Wang Chao-Hung , Huang Po-Hsun , Lin Feng-Yen , Lin Liang-Yu , Lin Shing-Jong , Chen Jaw-Wen 
Published: November 2019

AbstractVascular progenitors such as endothelial progenitor cells (EPCs) and smooth muscle-like progenitor cells (SMPCs) may play different roles in vascular repair.Ginkgo bilobaextract (GBE) is an exogenous activator of heme oxygenase (HO)-1, which has been suggested to improve vascular repair; however, the detailed mechanisms have yet to be elucidated. This study aimed to investigate whether GBE can modulate different vascular progenitor cells by activating HO-1 for vascular repair. A bone marrow transplantation mouse model was used to evaluate thein vivoeffects of GBE treatment on wire-injury induced neointimal hyperplasia, which is representative of impaired vascular repair. On day 14 of GBE treatment, the mice were subjected to wire injury of the femoral artery to identify vascular reendothelialization. Compared to the mice without treatment, neointimal hyperplasia was reduced in the mice that received GBE treatment for 28 days in a dose-dependent manner. Furthermore, GBE treatment increased bone marrow-derived EPCs, accelerated endothelial recovery, and reduced the number of SMPCs attached to vascular injury sites. The effects of GBE treatment on neointimal hyperplasia could be abolished by co-treatment with zinc protoporphyrin IX, an HO-1 inhibitor, suggesting thein vivorole of HO-1. In thisin vitrostudy, treatment with GBE activated human early and late EPCs and suppressed SMPC migration. These effects were abolished by HO-1 siRNA and an HO-1 inhibitor. Furthermore, GBE induced the expression of HO-1 by activating PI3K/Akt/eNOS signaling in human late EPCs and via p38 pathways in SMPCs, suggesting that GBE can induce HO-1in vitrothrough different molecular mechanisms in different vascular progenitor cells. Accordingly, GBE could activate early and late EPCs, suppress the migration of SMPCs, and improvein vivovascular repair after mechanical injury by activating HO-1, suggesting the potential role of pharmacological HO-1 activators, such as GBE, for vascular protection in atherosclerotic diseases.
Human pleural fluid triggers global changes in the transcriptional landscape of Acinetobacter baumannii as an adaptive response to stress
Authors: Martinez Jasmine , Fernandez Jennifer S. , Liu Christine , Hoard Amparo , Mendoza Anthony , Nakanouchi Jun , Rodman Nyah , Courville Robert , Tuttobene Marisel R. , Lopez Carolina , Gonzalez Lisandro J. , Shahrestani Parvin , Papp-Wallace Krisztina M. , Vila Alejandro J. , Tolmasky Marcelo E. , Bonomo Robert A. , Sieira Rodrigo , Ramirez Maria Soledad 
Published: November 2019

AbstractAcinetobacter baumannii is a feared, drug-resistant pathogen, characterized by its ability to resist extreme environmental and nutrient-deprived conditions. Previously, we showed that human serum albumin (HSA) can increase foreign DNA acquisition specifically and alter the expression of genes associated with pathogenicity. Moreover, in a recent genome-wide transcriptomic study, we observed that pleural fluid (PF), an HSA-containing fluid, increases DNA acquisition, can modulate cytotoxicity, and control immune responses by eliciting changes in the A. baumannii metabolic profile. In the present work, using more stringent criteria and focusing on the analysis of genes related to pathogenicity and response to stress, we analyzed our previous RNA-seq data and performed phenotypic assays to further explore the impact of PF on A. baumannii’s microbial behavior and the strategies used to overcome environmental stress. We observed that PF triggered differential expression of genes associated with motility, efflux pumps, antimicrobial resistance, biofilm formation, two-component systems (TCSs), capsule synthesis, osmotic stress, and DNA-damage response, among other categories. Phenotypic assays of A. baumannii A118 and two other clinical A. baumannii strains, revealed differences in their responses to PF in motility, biofilm formation, antibiotic susceptibility, osmotic stress, and outer membrane vesicle (OMV) production, suggesting that these changes are strain specific. We conclude that A. baumannii’s pathoadaptive responses is induced by HSA-containing fluids and must be part of this bacterium armamentarium to persist in hostile environments.