bluuebunny/crossref_metadata_2025_split huggingface dataset:
Security evaluation of quantum key distribution with weak basis-choice flaws
Authors: Sun Shi-Hai , Tian Zhi-Yu , Zhao Mei-Sheng , Ma Yan 
Published: October 2020

AbstractQuantum key distribution (QKD) can share an unconditional secure key between two remote parties, but the deviation between theory and practice will break the security of the generated key. In this paper, we evaluate the security of QKD with weak basis-choice flaws, in which the random bits used by Alice and Bob are weakly controlled by Eve. Based on the definition of Li et al. (Sci Rep 5:16200, 2015) and GLLP’s analysis, we obtain a tight and analytical bound to estimate the phase error and key rate for both the single photon source and the weak coherent source. Our approach largely increases the key rate from that of the original approach. Finally, we investigate and confirm the security of BB84-QKD with a practical commercial devices.
Direct signaling of TL1A-DR3 on fibroblasts induces intestinal fibrosis in vivo
Authors: Jacob Noam , Kumagai Kotaro , Abraham Jay P. , Shimodaira Yosuke , Ye Yuefang , Luu Justin , Blackwood Anna Y. , Castanon Sofi L. , Stamps Dalton T. , Thomas Lisa S. , Gonsky Rivkah , Shih David Q. , Michelsen Kathrin S. , Targan Stephan R. 
Published: October 2020

AbstractTumor necrosis factor-like cytokine 1A (TL1A, TNFSF15) is implicated in inflammatory bowel disease, modulating the location and severity of inflammation and fibrosis. TL1A expression is increased in inflamed mucosa and associated with fibrostenosing Crohn’s disease. Tl1a-overexpression in mice causes spontaneous ileitis, and exacerbates induced proximal colitis and fibrosis. Intestinal fibroblasts express Death-receptor 3 (DR3; the only know receptor for TL1A) and stimulation with TL1A induces activation in vitro. However, the contribution of direct TL1A-DR3 activation on fibroblasts to fibrosis in vivo remains unknown. TL1A overexpressing naïve T cells were transferred into Rag−/− , Rag−/− mice lacking DR3 in all cell types (Rag−/−Dr3−/−), or Rag−/− mice lacking DR3 only on fibroblasts (Rag−/−Dr3∆Col1a2) to induce colitis and fibrosis, assessed by clinical disease activity index, intestinal inflammation, and collagen deposition. Rag−/− mice developed overt colitis with intestinal fibrostenosis. In contrast, Rag−/−Dr3−/− demonstrated decreased inflammation and fibrosis. Despite similar clinical disease and inflammation as Rag−/−, Rag−/−Dr3∆Col1a2 exhibited reduced intestinal fibrosis and attenuated fibroblast activation and migration. RNA-Sequencing of TL1A-stimulated fibroblasts identified Rho signal transduction as a major pathway activated by TL1A and inhibition of this pathway modulated TL1A-mediated fibroblast functions. Thus, direct TL1A signaling on fibroblasts promotes intestinal fibrosis in vivo. These results provide novel insight into profibrotic pathways mediated by TL1A paralleling its pro-inflammatory effects.
Logarithmic encoding of ensemble time intervals
Authors: Ren Yue , Allenmark Fredrik , Müller Hermann J. , Shi Zhuanghua 
Published: October 2020

AbstractAlthough time perception is based on the internal representation of time, whether the subjective timeline is scaled linearly or logarithmically remains an open issue. Evidence from previous research is mixed: while the classical internal-clock model assumes a linear scale with scalar variability, there is evidence that logarithmic timing provides a better fit to behavioral data. A major challenge for investigating the nature of the internal scale is that the retrieval process required for time judgments may involve a remapping of the subjective time back to the objective scale, complicating any direct interpretation of behavioral findings. Here, we used a novel approach, requiring rapid intuitive ‘ensemble’ averaging of a whole set of time intervals, to probe the subjective timeline. Specifically, observers’ task was to average a series of successively presented, auditory or visual, intervals in the time range 300–1300 ms. Importantly, the intervals were taken from three sets of durations, which were distributed such that the arithmetic mean (from the linear scale) and the geometric mean (from the logarithmic scale) were clearly distinguishable. Consistently across the three sets and the two presentation modalities, our results revealed subjective averaging to be close to the geometric mean, indicative of a logarithmic timeline underlying time perception.
Development of a protein microarray-based diagnostic chip mimicking the skin prick test for allergy diagnosis
Authors: Kalli Marina , Blok Andrew , Jiang Long , Starr Nichola , Alcocer Marcos J. C. , Falcone Franco H. 
Published: October 2020

AbstractProtein microarrays have been successfully used for detection of allergen-specific IgE in patient sera. Here, we demonstrate proof-of-concept of a solid-phase technique coupling the high-throughput potential of protein microarrays with the biologically relevant readout provided by IgE reporter cells, creating a novel allergic sensitization detection system. Three proteins (κ-casein, timothy grass pollen extract, polyclonal anti-human IgE) were printed onto three different polymer-coated surfaces (aldehyde-, epoxy- and NHS ester-coated). ToF–SIMs analysis was performed to assess printed protein stability and retention during washing steps. NFAT-DsRed rat basophil leukemia cell attachment and retention during washing steps was assessed after treatment with various extracellular matrix proteins. NFAT-DsRed IgE reporter cells were sensitized with serum of an allergic donor, incubated on the printed slides, and cell activation determined using a microarray laser scanner. NFAT DsRed IgE reporter cell binding was significantly increased on all polymer surfaces after incubation with fibronectin and vitronectin, but not collagen or laminin. All surfaces supported printed protein stability during washing procedure, with epoxy- and NHS ester-coated surfaces showing best protein retention. Cell activation was significantly higher in NHS ester-coated slides after timothy grass pollen extract stimulation appearing a suitable substrate for further development of an automated allergy diagnosis system.
Sampling of the conformational landscape of small proteins with Monte Carlo methods
Authors: Heilmann Nana , Wolf Moritz , Kozlowska Mariana , Sedghamiz Elaheh , Setzler Julia , Brieg Martin , Wenzel Wolfgang 
Published: October 2020

AbstractComputer simulation provides an increasingly realistic picture of large-scale conformational change of proteins, but investigations remain fundamentally constrained by the femtosecond timestep of molecular dynamics simulations. For this reason, many biologically interesting questions cannot be addressed using accessible state-of-the-art computational resources. Here, we report the development of an all-atom Monte Carlo approach that permits the modelling of the large-scale conformational change of proteins using standard off-the-shelf computational hardware and standard all-atom force fields. We demonstrate extensive thermodynamic characterization of the folding process of the α-helical Trp-cage, the Villin headpiece and the β-sheet WW-domain. We fully characterize the free energy landscape, transition states, energy barriers between different states, and the per-residue stability of individual amino acids over a wide temperature range. We demonstrate that a state-of-the-art intramolecular force field can be combined with an implicit solvent model to obtain a high quality of the folded structures and also discuss limitations that still remain.
A novel bioassay for quantification of surface Cannabinoid receptor 1 expression
Authors: Rodríguez-Rodríguez Ismael , Kalafut Joanna , Czerwonka Arkadiusz , Rivero-Müller Adolfo 
Published: October 2020

AbstractThe cannabinoid receptor type 1 (CB1) plays critical roles in multiple physiological processes such as pain perception, brain development and body temperature regulation. Mutations on this gene (CNR1), results in altered functionality and/or biosynthesis such as reduced membrane expression, changes in mRNA stability or changes in downstream signaling that act as triggers for diseases such as obesity, Parkinson’s, Huntington’s, among others; thus, it is considered as a potential pharmacological target. To date, multiple quantification methods have been employed to determine how these mutations affect receptor expression and localization; however, they present serious disadvantages that may arise quantifying errors. Here, we describe a sensitive bioassay to quantify receptor surface expression; in this bioassay the Gaussia Luciferase (GLuc) was fused to the extracellular portion of the CB1. The GLuc activity was assessed by coelenterazine addition to the medium followed by immediate readout. Based on GLuc activity assay, we show that the GLuc signals corelate with CB1 localization, besides, we showed the assay’s functionality and reliability by comparing its results with those generated by previously reported mutations on the CNR1 gene and by using flow cytometry to determine the cell surface receptor expression. Detection of membrane-bound CB1, and potentially other GPCRs, is able to quickly screen for receptor levels and help to understand the effect of clinically relevant mutations or polymorphisms.
Acoustic preadaptation to transmit vocal individuality of savanna nightjars in noisy urban environments
Authors: Liang Shih-Hsiung , Walther Bruno Andreas , Jen Chia-Hung , Chen Chao-Chieh , Chen Yi-Chih , Shieh Bao-Sen 
Published: October 2020

AbstractAs urbanization has expanded dramatically, the impacts of urban noise on wildlife have drawn increasing attention. However, previous studies have focused primarily on diurnal songbirds and much less on nocturnal nonpasserines such as nightjars. The savanna nightjar has recently successfully colonized urban areas in Taiwan. Using 1925 calls recorded from 67 individuals, we first investigated the individual differences of the acoustic structures; and, for those acoustic variables with significant individual differences, we examined the correlation between the acoustic structures and the ambient noise levels. We then compared the transmission efficacy of vocal individuality among three sets of acoustic variables: all acoustic variables, noise-related variables, and noise-unrelated variables. Using seven artificial frequency-shifted calls to represent seven different individuals in playback-recording experiments, we also investigated the transmission efficacy of vocal individuality and variable accuracy in three different urban noise levels (high, medium, low). We found that all 30 acoustic variables derived from the acoustic structures demonstrated significant individual differences, and 14 frequency-based variables were negatively correlated with ambient noise levels. Although transmission efficacy was significantly affected by urban noise, individuality information was still transmitted with high accuracy. Furthermore, the noise-unrelated structures (which included the maximum frequency, the maximum amplitude frequency, and the mean frequency of the call) had a significantly higher transmission efficacy of vocal individuality than the noise-related variables (which included the minimum frequency, the frequency at the start and the end of the call) in both field observation and playback-recording experiments. We conclude that these noise-unrelated acoustic features may be one of the key preadaptations for this nocturnal nonpasserine to thrive so successfully in its newly adopted urban environment.
Cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies
Authors: Lu Victor M. , Jue Toni Rose , McDonald Kerrie L. 
Published: October 2020

AbstractGlioblastoma (GBM) is a malignant brain tumour with a dismal prognosis, despite best treatment by surgical resection, radiation therapy (RT) and chemotherapy with temozolomide (TMZ). Nanoparticle (NP) therapy is an emerging consideration due to the ability of NPs to be formulated and cross the blood brain barrier. Lanthanum oxide (La2O3) NPs are therapeutically advantageous due to the unique chemical properties of lanthanum making it cytotoxic to cancers, and able to enhance existing anti-cancer treatments. However, La2O3 NPs have yet to be thoroughly investigated in brain tumors. We show that these NPs can reach the brain after venous injection, penetrate into GBM cells via endocytosis, dissociate to be cytotoxic, and enhance the therapeutic effects of RT and TMZ. The mechanisms of cell death by La2O3 NPs were found to be multifaceted. Increasing NP concentration was correlated to increased intrinsic and extrinsic apoptosis pathway markers in a radical oxygen species (ROS)-dependent manner, as well as involving direct DNA damage and autophagic pathways within GBM patient-derived cell lines. NP interactions to sensitize GBM to RT and TMZ were shown to involve these pathways by enhancing ROS and apoptotic mechanisms. We therefore demonstrate the therapeutic potential of La2O3 NPs to treat GBM cells in vitro, and encourage translational exploration in the future.
Single molecule, near full-length genome sequencing of dengue virus
Authors: Adikari Thiruni N. , Riaz Nasir , Sigera Chathurani , Leung Preston , Valencia Braulio M. , Barton Kirston , Smith Martin A. , Bull Rowena A. , Li Hui , Luciani Fabio , Weeratunga Praveen , Thein Tun-Linn , Lim Vanessa W. X. , Leo Yee-Sin , Rajapakse Senaka , Fink Katja , Lloyd Andrew R. , Fernando Deepika , Rodrigo Chaturaka 
Published: October 2020

AbstractCurrent methods for dengue virus (DENV) genome amplification, amplify parts of the genome in at least 5 overlapping segments and then combine the output to characterize a full genome. This process is laborious, costly and requires at least 10 primers per serotype, thus increasing the likelihood of PCR bias. We introduce an assay to amplify near full-length dengue virus genomes as intact molecules, sequence these amplicons with third generation “nanopore” technology without fragmenting and use the sequence data to differentiate within-host viral variants with a bioinformatics tool (Nano-Q). The new assay successfully generated near full-length amplicons from DENV serotypes 1, 2 and 3 samples which were sequenced with nanopore technology. Consensus DENV sequences generated by nanopore sequencing had over 99.5% pairwise sequence similarity to Illumina generated counterparts provided the coverage was > 100 with both platforms. Maximum likelihood phylogenetic trees generated from nanopore consensus sequences were able to reproduce the exact trees made from Illumina sequencing with a conservative 99% bootstrapping threshold (after 1000 replicates and 10% burn-in). Pairwise genetic distances of within host variants identified from the Nano-Q tool were less than that of between host variants, thus enabling the phylogenetic segregation of variants from the same host.
Wide temporal horns are associated with cognitive dysfunction, as well as impaired gait and incontinence
Authors: Lilja-Lund Otto , Kockum Karin , Hellström Per , Söderström Lars , Nyberg Lars , Laurell Katarina 
Published: October 2020

AbstractThe association between morphology of the brain and symptoms of suspected idiopathic normal pressure hydrocephalus (iNPH) is largely unknown. We investigated how ventricular expansion (width of the temporal horns [TH], callosal angle [CA], and Evans’ index [EI]) related to symptom severity in suspected iNPH. Participants (n = 168; 74.9 years ± SD 6.7; 55% females) from the general population underwent neurological examination, computed tomography, and neuropsychological testing. Multiple linear regression analysis revealed that wide TH was independently associated with all examined iNPH symptoms (p < 0.01) except for fine-motor performance, whereas a narrow CA only was associated to specific motor and cognitive functions (p < 0.05). TH and EI correlated significantly with incontinence (rs0.17 and rs0.16;p < 0.05). In conclusion, wide TH was significantly associated with most iNPH-symptoms. This finding potentially reflects the complex nature of the hippocampus, however further studies are needed to demonstrate functional connectivity.
Nanofibrous asymmetric collagen/curcumin membrane containing aspirin-loaded PLGA nanoparticles for guided bone regeneration
Authors: Ghavimi Mohammad Ali , Bani Shahabadi Amirhossein , Jarolmasjed Seyedhosein , Memar Mohammad Yousef , Maleki Dizaj Solmaz , Sharifi Simin 
Published: October 2020

AbstractThe goal of the current study was to develop an asymmetric guided bone regeneration (GBR) membrane benefiting from curcumin and aspirin. The membrane was prepared using electrospinning technique and then was physic-chemically characterized by the conventional methods. The release profile of aspirin from the prepared membrane was also measured by ultraviolet spectrophotometry. Also, the antibacterial activities of the membrane was evaluated. We also assessed the in vitro effects of the prepared membrane on the biocompatibility and osteogenic differentiation of dental pulp stem cells (DPSCs), and evaluated in vivo bone regeneration using the prepared membrane in the defects created in both sides of the dog’s jaw by histology. The results from the characterization specified that the membrane was successfully prepared with monodispersed nanosized fibers, uniform network shaped morphology, negative surface charge and sustained release platform for aspirin. The membrane also showed antimicrobial effects against all tested bacteria. The presence of curcumin and aspirin in the asymmetric membrane enhanced osteogenic potential at both transcriptional and translational levels. The results of the animal test showed that the test area was completely filled with new bone after just 28 days, while the commercial membrane area remained empty. There was also a soft tissue layer above the new bone area in the test side. We suggested that the prepared membrane in this work could be used as a GBR membrane to keep soft tissue from occupying bone defects in GBR surgeries. Besides, the surgeries can be benefited from antibacterial activities and bone healing effects of this novel GBR membrane while, simultaneously, promoting bone regeneration.
The genetic architecture of appendicular lean mass characterized by association analysis in the UK Biobank study
Authors: Pei Yu-Fang , Liu Yao-Zhong , Yang Xiao-Lin , Zhang Hong , Feng Gui-Juan , Wei Xin-Tong , Zhang Lei 
Published: October 2020

AbstractAppendicular lean mass (ALM) is a heritable trait associated with loss of lean muscle mass and strength, or sarcopenia, but its genetic determinants are largely unknown. Here we conducted a genome-wide association study (GWAS) with 450,243 UK Biobank participants to uncover its genetic architecture. A total of 1059 conditionally independent variants from 799 loci were identified at the genome-wide significance level (p < 5 × 10−9), all of which were also significant at p < 5 × 10–5 in both sexes. These variants explained ~15.5% of the phenotypic variance, accounting for more than one quarter of the total ~50% GWAS-attributable heritability. There was no difference in genetic effect between sexes or among different age strata. Heritability was enriched in certain functional categories, such as conserved and coding regions, and in tissues related to the musculoskeletal system. Polygenic risk score prediction well distinguished participants with high and low ALM. The findings are important not only for lean mass but also for other complex diseases, such as type 2 diabetes, as ALM is shown to be a protective factor for type 2 diabetes.
A cell cycle-dependent CRISPR-Cas9 activation system based on an anti-CRISPR protein shows improved genome editing accuracy
Authors: Matsumoto Daisuke , Tamamura Hirokazu , Nomura Wataru 
Published: October 2020

AbstractThe development of genome editing systems based on the Cas9 endonuclease has greatly facilitated gene knockouts and targeted genetic alterations. Precise editing of target genes without off-target effects is crucial to prevent adverse effects in clinical applications. Although several methods have been reported to result in less off-target effects associated with the CRISPR technology, these often exhibit lower editing efficiency. Therefore, efficient, accurate, and innocuous CRISPR technology is still required. Anti-CRISPR proteins are natural inhibitors of CRISPR-Cas systems derived from bacteriophages. Here, the anti-CRISPR protein, AcrIIA4, was fused with the N terminal region of human Cdt1 that is degraded specifically in S and G2, the phases of the cell cycle when homology-directed repair (HDR) is dominant. Co-expression of SpyCas9 and AcrIIA4-Cdt1 not only increases the frequency of HDR but also suppress off-targets effects. Thus, the combination of SpyCas9 and AcrIIA4-Cdt1 is a cell cycle-dependent Cas9 activation system for accurate and efficient genome editing.
Modeling disk fragmentation and multiplicity in massive star formation
Authors: Oliva G. André , Kuiper R. 
Published: October 2020

Context. There is growing evidence that massive stars grow by disk accretion in a similar way to their low-mass counterparts. Early in evolution, these disks can achieve masses that are comparable to the current stellar mass, and therefore the forming disks are highly susceptible to gravitational fragmentation.
Aims. We investigate the formation and early evolution of an accretion disk around a forming massive protostar, focussing on its fragmentation physics. To this end, we follow the collapse of a molecular cloud of gas and dust, the formation of a massive protostar, the formation of its circumstellar disk, and the formation and evolution of the disk fragments.
Methods. We used a grid-based, self-gravity radiation hydrodynamics code including a sub-grid module for stellar evolution and dust evolution. We purposely do not use a sub-grid module for fragmentation such as sink particles to allow for all paths of fragment formation and destruction, but instead we keep the spatial grid resolution high enough to properly resolve the physical length scales of the problem, namely the pressure scale height and Jeans length of the disk. Simulations are performed on a grid in spherical coordinates with a logarithmic spacing of the grid cells in the radial direction and a cosine distribution of the grid cells in the polar direction, focusing the spatial resolution on the disk midplane. As a consequence, roughly 25% of the total number of grid cells, corresponding to ~26 million grid cells, are used to model the disk physics. These constitute the highest resolution simulations performed up to now on disk fragmentation around a forming massive star with the physics considered here. For a better understanding of the effects of spatial resolution and to compare our high-resolution results with previous lower resolution studies in the literature, we perform the same simulation at five different resolutions, each run differing in resolution from its predecessor by a factor of two.
Results. The cloud collapses and a massive (proto)star is formed in its center surrounded by a fragmenting Keplerian-like accretion disk with spiral arms. The fragments have masses of ~1 M⊙, and their continuous interactions with the disk, spiral arms, and other fragments result in eccentric orbits. Fragments form hydrostatic cores surrounded by secondary disks with spiral arms that also produce new fragments. We identified several mechanisms of fragment formation, interaction, and destruction. Central temperatures of the fragments can reach the hydrogen dissociation limit, form second Larson cores, and evolve into companion stars. Based on this, we study the multiplicity predicted by the simulations and find approximately six companions at different distances from the primary: from possible spectroscopic multiples, to companions at distances between 1000 and 2000 au.