bluuebunny/crossref_metadata_2025_split huggingface dataset:
An efficient and compact switch for quantum circuits
Authors: Wu Yulin , Yang Li-Ping , Gong Ming , Zheng Yarui , Deng Hui , Yan Zhiguang , Zhao Yanjun , Huang Keqiang , Clark Juno , Munro William J. , Nemoto Kae , Zheng Dong-Ning , Sun C. P. , Liu Yu-xi , Zhu Xiaobo , Lu Li 
Published: October 2018

Abstract
The engineering of quantum devices has reached the stage where we now have small-scale quantum processors containing multiple interacting qubits within them. Simple quantum circuits have been demonstrated and scaling up to larger numbers is underway. However, as the number of qubits in these processors increases, it becomes challenging to implement switchable or tunable coherent coupling among them. The typical approach has been to detune each qubit from others or the quantum bus it connected to, but as the number of qubits increases this becomes problematic to achieve in practice due to frequency crowding issues. Here, we demonstrate that by applying a fast longitudinal control field to the target qubit, we can turn off its couplings to other qubits or buses. This has important implications in superconducting circuits as it means we can keep the qubits at their optimal points, where the coherence properties are greatest, during coupling/decoupling process. Our approach suggests another way to control coupling among qubits and data buses that can be naturally scaled up to large quantum processors.
Trends in clinical trials for articular cartilage repair by cell therapy
Authors: Negoro Takaharu , Takagaki Yuri , Okura Hanayuki , Matsuyama Akifumi 
Published: October 2018

AbstractFocal and degenerative lesions of articular cartilage greatly reduce the patient’s quality of life. Various therapies including surgical treatment have been developed, but a definitive therapy is not yet known. Several cell therapy products have already been developed and are available in the market. In this study, we examined the clinical research trends related to cell therapy products in the cartilage repair field based on data obtained from the ClinicalTrial.gov website. Although this website does not provide comprehensive results of clinical trials, it offers information on prospective clinical trials, including work in progress, and thus allows for chronological analysis of the data. We selected 203 studies related to the field of cartilage regeneration from ClinicalTrial.gov. The results showed a shift in the clinical translational trend in utilized cells from cartilage- and bone marrow- to adipose tissue-based cells. Whereas the studies that used cartilage as the cell source included many phase III trials, fewer studies using bone marrow and adipose tissue cells progressed to phase III, suggesting that most clinical developments using the latter sources have not been successful so far. One product covered the entire period from the start of phase I to the completion of phase III, with a time to completion of more than 100 months. Translational trends in autologous chondrocyte implantation were also discussed. The use of ClinicalTrials.gov as the sole data source can yield a perspective view of the global clinical translational trends, which has been difficult to observe up to this point.
Male-specific association between subclinical hypothyroidism and the risk of non-alcoholic fatty liver disease estimated by hepatic steatosis index: Korea National Health and Nutrition Examination Survey 2013 to 2015
Authors: Lee Jeongmin , Ha Jeonghoon , Jo Kwanhoon , Lim Dong-Jun , Lee Jung-Min , Chang Sang-Ah , Kang Moo-Il , Cha Bong-Yun , Kim Min-Hee 
Published: October 2018

AbstractNon-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease encompassing a broad spectrum of pathologic changes in the liver. Metabolic derangements are suggested to be main causes of NAFLD. As thyroid hormone is a main regulator of energy metabolism, there may be a link between NAFLD and thyroid function. In previous studies, the association between NAFLD and thyroid function was not conclusive. The aim of this study was to clarify the relationship between NAFLD and thyroid function, focusing on subclinical hypothyroidism, using nationwide survey data representing the Korean population. NAFLD was defined as a hepatic steatosis index of 36 or higher. Based on the analysis of nationwide representative data, subclinical hypothyroidism was related to a high risk of NAFLD in males, but not in females. Our study showed that thyroid function might play a substantial role in the development of NAFLD, especially in males. Further study to elucidate the underlying mechanism of gender specific association of mild thyroid dysfunction and NAFLD would be required.
Bayesian spatiotemporal analysis for association of environmental factors with hand, foot, and mouth disease in Guangdong, China
Authors: Du Zhicheng , Lawrence Wayne R. , Zhang Wangjian , Zhang Dingmei , Yu Shicheng , Hao Yuantao 
Published: October 2018

AbstractHand, foot, and mouth disease (HFMD) remains a significant public health and economic burden in parts of China, particularly Guangdong Province. Although the association between meteorological factors and HFMD has been well documented, significant gaps remain in our understanding of the potential impact of environmental factors. Using county-level monthly HFMD data from China CDC and environmental data from multiple sources, we used spatiotemporal Bayesian models to evaluate the association between HFMD and environmental factors including vegetation index, proportion of artificial surface, road capacity, temperature and humidity, and assessed the spatial and temporal dynamic of the association. Statistically significant correlation coefficients from −0.056 to 0.36 (all P < 0.05) were found between HFMD incidence and all environmental factors. The contributions of these factors for HFMD incidence were estimated to be 16.32%, 12.31%, 14.61%, 13.53%, and 2.63%. All environmental factors including vegetation index (Relative Risk: 0.889; Credible Interval: 0.883–0.895), artificial surface (1.028; 1.022–1.034), road capacity (1.033; 1.028–1.038), temperature (1.039; 1.028–1.05), and relative humidity (1.015; 1.01–1.021) were statistically retained in the final spatiotemporal model. More comprehensive environmental factors were identified as associating with HFMD incidence. Taking these environmental factors into consideration for prevention and control strategy might be of great practical significance.
Heat-stress triggers MAPK crosstalk to turn on the hyperosmotic response pathway
Authors: Dunayevich Paula , Baltanás Rodrigo , Clemente José Antonio , Couto Alicia , Sapochnik Daiana , Vasen Gustavo , Colman-Lerner Alejandro 
Published: October 2018

AbstractCells make decisions based on a combination of external and internal signals. In yeast, the high osmolarity response (HOG) is a mitogen-activated protein kinase (MAPK) pathway that responds to a variety of stimuli, and it is central to the general stress response. Here we studied the effect of heat-stress (HS) on HOG. Using live-cell reporters and genetics, we show that HS promotes Hog1 phosphorylation and Hog1-dependent gene expression, exclusively via the Sln1 phosphorelay branch, and that the strength of the activation is larger in yeast adapted to high external osmolarity. HS stimulation of HOG is indirect. First, we show that HS causes glycerol loss, necessary for HOG activation. Preventing glycerol efflux by deleting the glyceroporin FPS1 or its regulators RGC1 and ASK10/RGC2, or by increasing external glycerol, greatly reduced HOG activation. Second, we found that HOG stimulation by HS depended on the operation of a second MAPK pathway, the cell-wall integrity (CWI), a well-known mediator of HS, since inactivating Pkc1 or deleting the MAPK SLT2 greatly reduced HOG activation. Our data suggest that the main role of the CWI in this process is to stimulate glycerol loss. We found that in yeast expressing the constitutively open channel mutant (Fps1-Δ11), HOG activity was independent of Slt2. In summary, we suggest that HS causes a reduction in turgor due to the loss of glycerol and the accompanying water, and that this is what actually stimulates HOG. Thus, taken together, our findings highlight a central role for Fps1, and the metabolism of glycerol, in the communication between the yeast MAPK pathways, essential for survival and reproduction in changing environments.
PAR-1 is a novel mechano-sensor transducing laminar flow-mediated endothelial signaling
Authors: Kim Suji , Han Jung-Hwa , Nam Dae-Hwan , Kim Geun-Young , Lim Jae Hyang , Kim Jae-Ryong , Woo Chang-Hoon 
Published: October 2018

AbstractRecent studies have indicated that protease-activated receptor-1 (PAR-1) is involved in cytoprotective and anti-inflammatory responses in endothelial cells (ECs). However, the role of PAR-1 in laminar flow-mediated atheroprotective responses remains unknown. Herein, we investigated whether PAR-1 regulates laminar flow-mediated mechanotransduction in ECs. Confocal analysis showed that PAR-1 was internalized into early endosomes in response to laminar flow. In addition, flow cytometry analysis showed that cell surface expression of PAR-1 was reduced by laminar flow, suggesting that PAR-1 was activated in response to laminar flow. Depletion of PAR-1 using human PAR-1 siRNA inhibited unidirectional laminar flow-mediated actin stress fiber formation and cellular alignment as well as atheroprotective gene expressions in HUVECs. Moreover, PAR-1 knockdown inhibited laminar flow-stimulated eNOS phosphorylation, and inhibited the phosphorylations of Src, AMPK, ERK5 and HDAC5. Furthermore, PAR-1 depletion inhibited laminar flow-mediated anti-inflammatory responses as demonstrated by reduced TNFα-induced VCAM-1 expression and by monocyte adhesion to HUVECs, and prevented laminar flow-mediated anti-apoptotic response. An investigation of the role of PAR-1 in vasomotor modulation using mouse aortic rings revealed that acetylcholine-induced vasorelaxation was diminished in PAR-1 deficient mice compared to littermate controls. Taken together, these findings suggest that PAR-1 be viewed as a novel pharmacologic target for the treatment of vascular diseases, including atherosclerosis.
A break in parental interaction does not affect the temporal dependency of infant social engagement, but disrupts non-social engagement
Authors: Mattson Whitney I. , Messinger Daniel S. , Gangi Devon N. , Myers Nicholas D. 
Published: October 2018

AbstractInfant looking patterns during interaction offer an early window into social and nonsocial engagement. Recent evidence indicates that infant looks exhibit temporal dependency—one look duration predicts the next look duration. It is unknown, however, whether temporal dependency emerges as infants structure their own looking or whether it is influenced by interaction. We examined whether a perturbation of social interaction affected temporal dependency. Using the Face-to-Face/Still-Face procedure, we compared temporal dependency during parental interaction (the Face-to-Face & Reunion episodes) to parental non-responsiveness (the Still-Face episode). Overall, the durations of successive infant looks were predictable; past behavior constrained current behavior. The duration of one look at the parent (Face Look) predicted the duration of the next Face Look. Likewise, the duration of a look at any place that was not the parent’s face (Away Look) predicted the duration of the next Away Look. The temporal dependency of Face Looks (social engagement) was unaffected by the Still-Face perturbation, but the temporal dependency of Away Looks (nonsocial engagement) declined during the Still-Face. Infant temporal structuring of engagement during social looking is not dependent on parental interaction while the disruption of interaction affects infants’ structuring of their own non-social engagement.
Antibiotic export by efflux pumps affects growth of neighboring bacteria
Authors: Wen Xi , Langevin Ariel M. , Dunlop Mary J. 
Published: October 2018

AbstractCell-cell interactions play an important role in bacterial antibiotic resistance. Here, we asked whether neighbor proximity is sufficient to generate single-cell variation in antibiotic resistance due to local differences in antibiotic concentrations. To test this, we focused on multidrug efflux pumps because recent studies have revealed that expression of pumps is heterogeneous across populations. Efflux pumps can export antibiotics, leading to elevated resistance relative to cells with low or no pump expression. In this study, we co-cultured cells with and without AcrAB-TolC pump expression and used single-cell time-lapse microscopy to quantify growth rate as a function of a cell’s neighbors. In inhibitory concentrations of chloramphenicol, we found that cells lacking functional efflux pumps (ΔacrB) grow more slowly when they are surrounded by cells with AcrAB-TolC pumps than when surrounded by ΔacrB cells. To help explain our experimental results, we developed an agent-based mathematical model, which demonstrates the impact of neighbors based on efflux efficiency. Our findings hold true for co-cultures of Escherichia coli with and without pump expression and also in co-cultures of E. coli and Salmonella typhumirium. These results show how drug export and local microenvironments play a key role in defining single-cell level antibiotic resistance.
Quantitative B-lymphocyte deficiency and increased TCRγδ T-lymphocytes in acute infectious spondylodiscitis
Authors: Haugaard Anna K. , Marquart Hanne V. , Kolte Lilian , Ryder Lars Peter , Kehrer Michala , Krogstrup Maria , Dragsted Ulrik B. , Dahl Benny , Gjørup Ida E. , Andersen Åse B. , Garred Peter , Nielsen Susanne D. 
Published: October 2018

AbstractAcute infectious spondylodiscitis (AIS) is a serious infection of the spine with rising incidence and a mortality of 3–6%. The role of the immune system in AIS is largely unknown. We performed extensive B and T-lymphocyte phenotyping in patients with AIS at diagnosis and after treatment cessation. In this prospective multicentre study, flow cytometric analysis of T and B-lymphocyte subsets was performed in 35 patients at diagnosis and 3 months after treatment cessation. We additionally analysed levels of immunoglobulins and IgG subclasses, serum level and genetic variants of mannose-binding lectin, and somatic hypermutation. A total of 22 (61%) patients had B-lymphocytes below reference limit at baseline, persisting in 7 (30%) patients at follow-up. We found a lower proportion of CD19 + CD27 + IgD+ marginal zone B-lymphocytes and a higher proportion of γδ+ T-lymphocyte receptors compared with controls at both time points. Immunoglobulin levels were elevated at baseline compared to follow-up, and not associated with absolute B-lymphocyte count. In conclusion, a large proportion of AIS patients presented with profound B-lymphocyte deficiency, only partly reversible at follow-up. Identification of immune dysfunction related to AIS may allow for future targeted therapeutic interventions to restore host immunity.
The effects of aquarium culture on coral oocyte ultrastructure
Authors: Lin Chiahsin , Zhuo Jian-Ming , Chong Gabriella , Wang Li-Hsueh , Meng Pei-Jie , Tsai Sujune 
Published: October 2018

AbstractAs the world’s oceans are currently threatened by anthropogenic pollution and climate change, coral breeding has become an important conservation method, since it can limit marine organisms’ exposure to sub-optimal environment conditions. However, the aquarium environment is inherently different from the ocean, and this could manifest in physiological changes in the reared organisms, particularly with respect to their reproduction. Therefore, the aim of this study was to observe and compare the ultrastructure of the oocytes from wild Oxypora lacera and Echinopora gemmacea with the oocytes from cultured corals using transmission electron microscope. The oocytes from Wild O. lacera and E. gemmacea were larger than cultured ones, though their microvillus layers were significantly thiner. Internally, lipid granule areas and yolk material density in the oocytes of wild O. lacera and E. gemmacea were ~25% lower than in their cultured counterparts. Food availability and the presence and availability of symbiotic dinoflagellates (genus Symbiodinium) may have played a role in driving these lipid-based differences, in particular, as cultured corals had limited potential for heterotrophic feeding. These data will aid in future coral husbandry efforts.
Glutamate alleviates intestinal injury, maintains mTOR and suppresses TLR4 and NOD signaling pathways in weanling pigs challenged with lipopolysaccharide
Authors: Qin Qin , Xu Xiao , Wang Xiuying , Wu Huanting , Zhu Huiling , Hou Yongqing , Dai Bing , Liu Xiuting , Liu Yulan 
Published: October 2018

AbstractThis experiment aimed to explore whether glutamate (Glu) had beneficial effects on intestinal injury caused by Escherichia coli LPS challenge via regulating mTOR, TLRs, as well as NODs signaling pathways. Twenty-four piglets were allotted to 4 treatments including: (1) control group; (2) LPS group; (3) LPS + 1.0% Glu group; (4) LPS + 2.0% Glu group. Supplementation with Glu increased jejunal villus height/crypt depth ratio, ileal activities of lactase, maltase and sucrase, and RNA/DNA ratio and protein abundance of claudin-1 in jejunum and ileum. In addition, the piglets fed Glu diets had higher phosphorylated mTOR (Ser2448)/total mTOR ratio in jejunum and ileum. Moreover, Glu decreased TNF-α concentration in plasma. Supplementation with Glu also decreased mRNA abundance of jejunal TLR4, MyD88, IRAK1, TRAF6, NOD2 and increased mRNA abundance of ileal Tollip. These results indicate that Glu supplementation may be closely related to maintaining mTOR and inhibiting TLR4 and NOD signaling pathways, and concomitant improvement of intestinal integrity under an inflammatory condition.
Floristic diversity in different urban ecological niches of a southern European city
Authors: Salinitro Mirko , Alessandrini Alessandro , Zappi Alessandro , Melucci Dora , Tassoni Annalisa 
Published: October 2018

AbstractThe present paper aimed at studying the vertical and horizontal spatial distribution, species richness and diversity of vascular plants in different urban ecological niches (urban habitats) by means of the case study of Bologna (Italy), a typical densely populated southern European city. A total of 477 species were found in the study area of the historical city centre, 30% of which were alien species. Alien plant species were mainly present among phanerophytes, while native plants were mainly therophytes and hemicryptophytes. The habitats that mostly contributed to the species total richness were semi-natural soils, followed by paved areas, walls, rooftops and manholes. The number of exclusive species decreased according to the selectiveness of the habitat, with manholes and rooftops being the most selective. The presence of hemicryptophytes constant decreased going from 27% of more humid habitats to 5% of more arid habitats, so that they can be considered a water availability biomarker. Urban habitat quality, measured by the number of native species, was directly proportional to the strength of selective factors and inversely proportional to the rate of disturbance, with roofs and semi-natural soils having, respectively, the highest and lowest quality. Finally, a relation between species richness and street characteristics, like width, orientation and type of flooring, was demonstrated.
Placental FKBP51 mediates a link between second trimester maternal anxiety and birthweight in female infants
Authors: Togher Katie L. , O’Keeffe Gerard W. , Khashan Ali S. , Clarke Gerard , Kenny Louise C. 
Published: October 2018

AbstractPrenatal distress is associated with adverse outcomes in affected offspring. Alterations in placental glucocorticoid signalling and subsequent foetal overexposure to glucocorticoids have been implicated as an underlying mechanism. Infant sex is emerging as an important factor in disease susceptibility. This study aimed to examine the effects of maternal distress across pregnancy on birth outcomes and placental glucocorticoid genes in a sex-dependent manner. Participants completed psychological distress questionnaires throughout pregnancy. Placental HSD11B2, NR3C1 and FKBP51 were analysed by real time PCR and cortisol was measured in new-born hair. Second trimester stress was negatively correlated with birthweight in males and positively correlated with placental NR3C1 mRNA in females. Second trimester anxiety was negatively correlated with birthweight and placental FKBP51 mRNA in females. In mediation analysis, placental FKBP51 mRNA expression was found to mediate the link between prenatal anxiety and birthweight. New-born cortisol was negatively correlated with second trimester anxiety and positively correlated with female placental FKBP51 mRNA levels. Again, FKBP51 mRNA was found to mediate the link between anxiety and new-born cortisol. These results highlight a role for FKBP51 in the placental response to prenatal distress in females. The precise role that placental FKBP51 has in foetal and infant development has not been extensively studied and warrants further investigations.
2.0 Å resolution crystal structure of human polκ reveals a new catalytic function of N-clasp in DNA replication
Authors: Jha Vikash , Ling Hong 
Published: October 2018

AbstractHuman polymerase kappa (polκ) is a distinct Y-family DNA polymerase with a unique N-terminal N-clasp domain. The N-clasp renders polκ’s high efficiency and accuracy in DNA replication and lesion bypass. How N-clasp empowers polκ in replication remains unclear due to the disordering of N-clasp. Here, we present a 2.0-Å resolution crystal structure of a polκ ternary complex with DNA and an incoming nucleotide. The structure-function study reveals an ordered N-clasp domain that brings conserved and functionally important residues in contact with the replicating basepair in the active site and contributes to the nucleotidyl transfer reaction. Particularly, a fully ordered Lys25 from the N-clasp domain is in H-bonding with the α- and γ-phosphates of the incoming nucleotide. K25A mutation reduces the polymerase activity of polκ significantly. This lysine is structurally analogous to a conserved lysine in the A-family DNA polymerases in the closed form. In contrast, Lys25 in the previous structures of polκ does not have any contacts with the incoming nucleotide, resembling an open form of a DNA polymerase. Based on structural and functional similarity, we propose a local open/closed mechanism for polκ in DNA replication catalysis, which mimics the common mechanism for all DNA polymerases.
Engineering a branching sucrase for flavonoid glucoside diversification
Authors: Malbert Yannick , Moulis Claire , Brison Yoann , Morel Sandrine , André Isabelle , Remaud-Simeon Magali 
Published: October 2018

AbstractEnzymatic glycosylation of flavonoids is an efficient mean to protect aglycons against degradation while enhancing their solubility, life time and, by extension, their bioavailability which is critical for most of their applications in health care. To generate a valuable enzymatic platform for flavonoid glucosylation, an α-1,2 branching sucrase belonging to the family 70 of glycoside-hydrolases was selected as template and subsequently engineered. Two libraries of variants targeting pair-wise mutations inferred by molecular docking simulations were generated and screened for quercetin glucosylation using sucrose as a glucosyl donor. Only a limited number of variants (22) were retained on the basis of quercetin conversion and product profile. Their acceptor promiscuity towards five other flavonoids was subsequently assessed, and the automated screening effort revealed variants showing remarkable ability for luteolin, morin and naringenin glucosylation with conversion ranging from 30% to 90%. Notably, naringenin and morin, a priori considered as recalcitrant compounds to glucosylation using this α-transglucosylases, could also be modified. The approach reveals the potential of small platforms of engineered GH70 α-transglucosylases and opens up the diversity of flavonoid glucosides to molecular structures inaccessible yet.