bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metastable brain waves
Authors: Roberts James A. , Gollo Leonardo L. , Abeysuriya Romesh G. , Roberts Gloria , Mitchell Philip B. , Woolrich Mark W. , Breakspear Michael 
Published: March 2019

AbstractTraveling patterns of neuronal activity—brain waves—have been observed across a breadth of neuronal recordings, states of awareness, and species, but their emergence in the human brain lacks a firm understanding. Here we analyze the complex nonlinear dynamics that emerge from modeling large-scale spontaneous neural activity on a whole-brain network derived from human tractography. We find a rich array of three-dimensional wave patterns, including traveling waves, spiral waves, sources, and sinks. These patterns are metastable, such that multiple spatiotemporal wave patterns are visited in sequence. Transitions between states correspond to reconfigurations of underlying phase flows, characterized by nonlinear instabilities. These metastable dynamics accord with empirical data from multiple imaging modalities, including electrical waves in cortical tissue, sequential spatiotemporal patterns in resting-state MEG data, and large-scale waves in human electrocorticography. By moving the study of functional networks from a spatially static to an inherently dynamic (wave-like) frame, our work unifies apparently diverse phenomena across functional neuroimaging modalities and makes specific predictions for further experimentation.
Tensor network simulation of multi-environmental open quantum dynamics via machine learning and entanglement renormalisation
Authors: Schröder Florian A. Y. N. , Turban David H. P. , Musser Andrew J. , Hine Nicholas D. M. , Chin Alex W. 
Published: March 2019

AbstractThe simulation of open quantum dynamics is a critical tool for understanding how the non-classical properties of matter might be functionalised in future devices. However, unlocking the enormous potential of molecular quantum processes is highly challenging due to the very strong and non-Markovian coupling of ‘environmental’ molecular vibrations to the electronic ‘system’ degrees of freedom. Here, we present an advanced but general computational strategy that allows tensor network methods to effectively compute the non-perturbative, real-time dynamics of exponentially large vibronic wave functions of real molecules. We demonstrate how ab initio modelling, machine learning and entanglement analysis can enable simulations which provide real-time insight and direct visualisation of dissipative photophysics, and illustrate this with an example based on the ultrafast process known as singlet fission.
Intracellular hydrogelation preserves fluid and functional cell membrane interfaces for biological interactions
Authors: Lin Jung-Chen , Chien Chen-Ying , Lin Chi-Long , Yao Bing-Yu , Chen Yuan-I , Liu Yu-Han , Fang Zih-Syun , Chen Jui-Yi , Chen Wei-ya , Lee No-No , Chen Hui-Wen , Hu Che-Ming J. 
Published: March 2019

AbstractCell membranes are an intricate yet fragile interface that requires substrate support for stabilization. Upon cell death, disassembly of the cytoskeletal network deprives plasma membranes of mechanical support and leads to membrane rupture and disintegration. By assembling a network of synthetic hydrogel polymers inside the intracellular compartment using photo-activated crosslinking chemistry, we show that the fluid cell membrane can be preserved, resulting in intracellularly gelated cells with robust stability. Upon assessing several types of adherent and suspension cells over a range of hydrogel crosslinking densities, we validate retention of surface properties, membrane lipid fluidity, lipid order, and protein mobility on the gelated cells. Preservation of cell surface functions is further demonstrated with gelated antigen presenting cells, which engage with antigen-specific T lymphocytes and effectively promote cell expansion ex vivo and in vivo. The intracellular hydrogelation technique presents a versatile cell fixation approach adaptable for biomembrane studies and biomedical device construction.
Probabilistic variable-length segmentation of protein sequences for discriminative motif discovery (DiMotif) and sequence embedding (ProtVecX)
Authors: Asgari Ehsaneddin , McHardy Alice C. , Mofrad Mohammad R. K. 
Published: March 2019

AbstractIn this paper, we present peptide-pair encoding (PPE), a general-purpose probabilistic segmentation of protein sequences into commonly occurring variable-length sub-sequences. The idea of PPE segmentation is inspired by the byte-pair encoding (BPE) text compression algorithm, which has recently gained popularity in subword neural machine translation. We modify this algorithm by adding a sampling framework allowing for multiple ways of segmenting a sequence. PPE segmentation steps can be learned over a large set of protein sequences (Swiss-Prot) or even a domain-specific dataset and then applied to a set of unseen sequences. This representation can be widely used as the input to any downstream machine learning tasks in protein bioinformatics. In particular, here, we introduce this representation through protein motif discovery and protein sequence embedding. (i) DiMotif: we present DiMotif as an alignment-free discriminative motif discovery method and evaluate the method for finding protein motifs in three different settings: (1) comparison of DiMotif with two existing approaches on 20 distinct motif discovery problems which are experimentally verified, (2) classification-based approach for the motifs extracted for integrins, integrin-binding proteins, and biofilm formation, and (3) in sequence pattern searching for nuclear localization signal. The DiMotif, in general, obtained high recall scores, while having a comparable F1 score with other methods in the discovery of experimentally verified motifs. Having high recall suggests that the DiMotif can be used for short-list creation for further experimental investigations on motifs. In the classification-based evaluation, the extracted motifs could reliably detect the integrins, integrin-binding, and biofilm formation-related proteins on a reserved set of sequences with high F1 scores. (ii) ProtVecX: we extend k-mer based protein vector (ProtVec) embedding to variablelength protein embedding using PPE sub-sequences. We show that the new method of embedding can marginally outperform ProtVec in enzyme prediction as well as toxin prediction tasks. In addition, we conclude that the embeddings are beneficial in protein classification tasks when they are combined with raw amino acids k-mer features.
Vertical disc tilt and features of the optic nerve head anatomy are related to visual field defect in myopic eyes
Authors: Park Hae-Young Lopilly , Kim Yong Chan , Jung Younhea , Park Chan Kee 
Published: March 2019

AbstractMyopia is significantly growing eye disease which accompanies various ocular pathologies including glaucoma. Understanding visual field (VF) and retinal nerve fiber layer (RNFL) damage observed in myopic eyes is important. Therefore, we evaluated optic disc margin anatomy using spectral-domain (SD) optical coherence tomography (OCT). We enrolled 40 healthy myopic patients and 64 myopic patients with RNFL defects in the superonasal region of the optic disc on red-free photographs and OCT. Optic disc stereophotographs were co-localized to SD-OCT images, and we analyzed the frequency with which the disc margin identified in photographs coincided with Bruch’s membrane (BM) opening, BM/border tissue, or border tissue. For each scan, the presence of border tissue overhang beyond the clinical disc margin and the end of Bruch’s membrane was identified. Among 64 myopic eyes with RNFL defects, 42 had corresponding inferotemporal VF defects. Border tissue overhang was found from 25 to 60% of myopic eyes with RNFL defect at all clock positions. However, border tissue overhang was found from 86 to 97% at 1, 2, 11 and 12 o’clock position in myopic eyes with VF defects. This was significantly different from myopic healthy eyes. We suggest that the OCT structure at the disc margin might contribute to VF damage in myopic patients.
Characterization of Plaque-Sized Variants of Daniel’s (DA) Strain in Theiler’s Virus-Induced Epilepsy
Authors: Bijalwan M. , Young C. R. , Tingling J. , Zhou X. J. , Rimmelin A. R. , Leibowitz J. L. , Welsh C. J. 
Published: March 2019

AbstractEpilepsy is a complex neurological disease characterized by recurrent seizures. Patients with viral encephalitis have a 16-fold increased risk of developing epilepsy, and this risk can persist for about 15 years after the occurrence of initial viral infection. Theiler’s murine encephalomyelitis virus (TMEV) infection induces a well-characterized experimental model of epilepsy in C57BL/6 mice. In response to intracerebral (I.C.) injection of Daniel’s (DA) strain of TMEV, there is vigorous immune response, which is detrimental to neurons and contributes to acute seizures, rendering mice susceptible to epilepsy. A comparativein vivochallenge study with either one of the two variants of the DA strain, small (DA-DS) or large (DA-CL) plaque forming variants, revealed differences in the diseases they induced in C57BL/6 mice. Compared to DA-CL-, DA-DS-infected mice exhibited significantly more seizures, higher clinical scores, neuroinflammation, and neuronal damage (mainly in the CA1-CA2 regions of hippocampus). Moreover, the brains of DA-DSinfected mice contained approximately five-fold higher virus than those of DA-CLinfected mice. A sequence comparison of the DA-CLand DA-DSgenome sequences showed mutations in the leader (L) and L* proteins of DA-CLvariant, which may be the cause of attenuating phenotype of DA-CLvariant in the C57BL/6 mouse model of epilepsy.
Long Non-coding RNAs Coordinate Developmental Transitions and Other Key Biological Processes in Grapevine
Authors: Bhatia Garima , Sharma Shailesh , Upadhyay Santosh Kumar , Singh Kashmir 
Published: March 2019

AbstractLong non-coding RNAs (lncRNAs) are transcripts >200 nucleotides that have prominently surfaced as dynamic regulatory molecules. Using computational approaches, we identified and characterized 56,441 lncRNAs in grapevine (Vitis vinifera) by harnessing RNA-seq data from 10 developmental stages of leaf, inflorescence, and berry tissues. We conducted differential expression analysis and determined tissue- and developmental stage-specificity of lncRNAs in grapevine, which indicated their spatiotemporal regulation. Functional annotation using co-expression analysis revealed their involvement in regulation of developmental transitions in sync with transcription factors (TFs). Further, pathway enrichment analysis revealed lncRNAs associated with biosynthetic and secondary metabolic pathways. Additionally, we identified 115, 560, and 133 lncRNAs as putative miRNA precursors, targets, and endogenous target mimics, respectively, which provided an insight into the interplay of regulatory RNAs. We also explored lncRNA-mediated regulation of extra-chromosomal genes–i.e., mitochondrial and chloroplast coding sequences and observed their involvement in key biological processes like ‘photosynthesis’ and ‘oxidative phosphorylation’. In brief, these transcripts coordinate important biological functions via interactions with both coding and non-coding RNAs as well as TFs in grapevine. Our study would facilitate future experiments in unraveling regulatory mechanisms of development in this fruit crop of economic importance.
Continuously Frequency-Tuneable Plasmonic Structures for Terahertz Bio-sensing and Spectroscopy
Authors: Deng Xiangying , Li Leyang , Enomoto Mitsuhiro , Kawano Yukio 
Published: March 2019

AbstractPlasmon-based devices are powerful for use in highly sensitive evanescent-field detection and analysis, but they exhibit the problem of limited frequency tunability for fixed structures. This feature causes problems in the multi-frequency investigations required for materials characterization, bio-related research, etc. Here, we propose and fabricate a spiral-shaped plasmonic structure that enables a continuous frequency-tuneable evanescent-field concentration in the terahertz (THz) region with simple operation. The device also increases the electric field intensity at the subwavelength aperture, thus significantly amplifying the transmission. Highly tuneable transmission bands are observed by simply rotating the spiral plasmonic structure, which are in good agreement with the behaviour expected from electromagnetic simulation. Medical examinations are performed by measuring the interactions between the frequency-tuneable plasmons and bio-samples, which enables observing distinct tissue-dependent transmission spectra and images. The developed device simultaneously offers the advantages of both plasmonic devices and frequency-tuneable devices, which can increase the availability and versatility of evanescent-field THz sensing and analysis. The mechanism presented will shed light on THz plasmonics and motivate the implementation of a variety of applications based on plasmon-mediated THz technologies.
Speed tuning properties of mirror symmetry detection mechanisms
Authors: Sharman Rebecca J. , Gheorghiu Elena 
Published: March 2019

AbstractThe human visual system is often tasked with extracting image properties such as symmetry from rapidly moving objects and scenes. The extent to which motion speed and symmetry processing mechanisms interact is not known. Here we examine speed-tuning properties of symmetry detection mechanisms using dynamic dot-patterns containing varying amounts of position and local motion-direction symmetry. We measured symmetry detection thresholds for stimuli in which symmetric and noise elements either drifted with different relative speeds, were relocated at different relative temporal frequencies or were static. We also measured percentage correct responses under two stimulus conditions: a segregated condition in which symmetric and noise elements drifted at different speeds, and a non-segregated condition in which the symmetric elements drifted at two different speeds in equal proportions, as did the noise elements. We found that performance (i) improved gradually with increasing the difference in relative speed between symmetric and noise elements, but was invariant across relative temporal frequencies/lifetime duration differences between symmetric and noise elements, (ii) was higher in the segregated compared to non-segregated conditions, and in the moving compared to the static conditions. We conclude that symmetry detection mechanisms are broadly tuned to speed, with speed-selective symmetry channels combining their outputs by probability summation.
A thin layer of sucrose octasulfate protects the oesophageal mucosal epithelium in reflux oesophagitis
Authors: Hayakawa Takuya , Kawasaki Shizuka , Hirayama Yutaka , Tsutsui Takuya , Sugiyama Eiji , Adachi Kiyo , Kon Ryo , Suematsu Makoto , Sugiura Yuki 
Published: March 2019

AbstractSucralfate is effective for the treatment of gastric and duodenal ulcers owing to its protective gel-forming ability. However, the mechanism by which sucralfate protects the oesophageal mucosa against reflux oesophagitis has not been clarified. We aimed to investigate the mechanisms of action of sucralfate and sucrose octasulfate (SOS), a component of sucralfate. SOS and sucralfate were administered to oesophagitis-induced rats, and the ulcer lesion size was macroscopically examined and scored. Effective pepsin activity in the gastric juices obtained from the animal model was evaluated by a casein digestion test. Sucralfate and SOS improved the pathology scores in a dose-dependent manner, whereas gastric juice pepsin activity was not impaired by therapeutic doses of SOS. As SOS lacks the ability to form a thick gel layer by polymerisation, we examined the distribution of SOS in the mucosal lumen by imaging mass spectrometry (IMS) to determine whether SOS directly adheres to the mucosal surface. A clear homogeneous thin-layer SOS film (>100 μm thick) was visualized on the oesophageal mucosal surface. Moreover, this SOS film formation was enhanced at ulcer lesion sites. Taken together, SOS appears to protect oesophageal mucosa against reflux oesophagitis via thin-layer formation on the mucosal surface.
A retinal model of cerebral malaria
Authors: Paquet-Durand François , Beck Susanne C. , Das Soumyaparna , Huber Gesine , Le Chang  , Schubert Timm , Tanimoto Naoyuki , Garcia-Garrido Marina , Mühlfriedel Regine , Bolz Sylvia , Hoffmann Wolfgang , Schraermeyer Ulrich , Mordmüller Benjamin , Seeliger Mathias W. 
Published: March 2019

AbstractMalaria is a causative factor in about 500.000 deaths each year world-wide. Cerebral malaria is a particularly severe complication of this disease and thus associated with an exceedingly high mortality. Malaria retinopathy is an ocular manifestation often associated with cerebral malaria, and presumably shares a substantial part of its pathophysiology. Here, we describe that indeed murine malaria retinopathy reproduced the main hallmarks of the corresponding human disease. In the living animal, we were able to follow the circulation and cellular localization of malaria parasites transgenically labelled with GFP via non-invasive in vivo retinal imaging. We found that malaria parasites cross the blood-retinal-barrier and infiltrate the neuroretina, concomitant with an extensive, irreversible, and long-lasting retinal neurodegeneration. Furthermore, anti-malarial treatment with dihydroartemisinin strongly diminished the load of circulating parasites but resolved the symptoms of the retinopathy only in part. In summary, we introduce here a novel preclinical model for human cerebral malaria that is much more directly accessible for studies into disease pathophysiology and development of novel treatment approaches. In vivo retinal imaging may furthermore serve as a valuable tool for the early diagnosis of the human disease.
Quantum Oscillations from Nontrivial States in Quasi-Two-Dimensional Dirac Semimetal ZrTe5 Nanowires
Authors: Yang Pei , Wang Wei , Zhang Xiaoqian , Wang Kejie , He Liang , Liu Wenqing , Xu Yongbing 
Published: March 2019

AbstractRecently discovered Dirac semimetal ZrTe5 bulk crystal, exhibits nontrivial conducting states in each individual layer, holding great potential for novel spintronic applications. Here, to reveal the transport properties of ZrTe5, we fabricated ZrTe5 nanowires (NWs) devices, with much larger surface-to-volume ratio than bulk materials. Quantum oscillations induced by the two-dimensional (2D) nontrivial conducting states have been observed from these NWs and a finite Berry phase of ~π is obtained by the analysis of Landau-level fan diagram. More importantly, the absence of the Aharonov-Bohm (A-B) oscillations, along with the SdH oscillations, suggests that the electrons only conduct inside each layer. And the intralayer conducting is suppressed because of the weak connection between adjacent layers. Our results demonstrate that ZrTe5 NWs can serve as a suitable quasi-2D Dirac semimetal with high mobility (~85000 cm2V−1s−1) and large nontrivial conductance contribution (up to 8.68%).
Extensive reprogramming of the nascent transcriptome during iPSC to hepatocyte differentiation
Authors: Viiri Leena E. , Rantapero Tommi , Kiamehr Mostafa , Alexanova Anna , Oittinen Mikko , Viiri Keijo , Niskanen Henri , Nykter Matti , Kaikkonen Minna U. , Aalto-Setälä Katriina 
Published: March 2019

AbstractHepatocyte-like cells (HLCs) derived from induced pluripotent stem cells (iPSCs) provide a renewable source of cells for drug discovery, disease modelling and cell-based therapies. Here, by using GRO-Seq we provide the first genome-wide analysis of the nascent RNAs in iPSCs, HLCs and primary hepatocytes to extend our understanding of the transcriptional changes occurring during hepatic differentiation process. We demonstrate that a large fraction of hepatocyte-specific genes are regulated at transcriptional level and identify hundreds of differentially expressed non-coding RNAs (ncRNAs), including primary miRNAs (pri-miRNAs) and long non-coding RNAs (lncRNAs). Differentiation induced alternative transcription start site (TSS) usage between the cell types as evidenced for miR-221/222 and miR-3613/15a/16-1 clusters. We demonstrate that lncRNAs and coding genes are tightly co-expressed and could thus be co-regulated. Finally, we identified sets of transcriptional regulators that might drive transcriptional changes during hepatocyte differentiation. These included RARG, E2F1, SP1 and FOXH1, which were associated with the down-regulated transcripts, and hepatocyte-specific TFs such as FOXA1, FOXA2, HNF1B, HNF4A and CEBPA, as well as RXR, PPAR, AP-1, JUNB, JUND and BATF, which were associated with up-regulated transcripts. In summary, this study clarifies the role of regulatory ncRNAs and TFs in differentiation of HLCs from iPSCs.
Neural correlates of early adversity among Bangladeshi infants
Authors: Jensen Sarah K. G. , Kumar Swapna , Xie Wanze , Tofail Fahmida , Haque Rashidul , Petri William A. , Nelson Charles A. 
Published: March 2019

AbstractIn this paper we explore the relationship between the Visual Evoked Potential (VEP), a component of the electroencephalogram elicited by visual stimuli, and cognitive functions in children growing up in an urban slum in Bangladesh. VEPs in response to pattern-reversing checkerboards were collected in 6 month-old-infants (n = 91) and 36-month-old children (n = 112). We examine variation in the amplitude and latency of the first positive component, the P1, of the VEP in relation to cognitive scores on the Mullen Scales of Early Learning and the Wechsler Preschool and Primary Scale of Intelligence. We also examine whether children’s caregiving experiences prior to the neuro-cognitive assessment explain variation in the P1 of the VEP. We find that the P1 amplitude of the VEP is related to concurrent cognitive performance in each respective cohort. We also find that the P1 amplitude at 6 months is prospectively associated with cognitive outcomes at 27 months, and the P1 amplitude at 36 months is prospectively associated with children’s IQ at 60 months. We find no associations between caregiving experiences and variation in the P1 of the VEP at 6 months, yet caregiving experience do explain variation in the P1 amplitude at 36 months. Caregiving experiences also explain variation in children’s concurrent and prospective cognitive functioning. The VEP may be used as a biomarker to index the neurobiological embedding of early adversity, which in turn may impact children’s cognitive functions.
Trimethylation of Elongation Factor-Tu by the Dual Thermoregulated Methyltransferase EftM Does Not Impact Its Canonical Function in Translation
Authors: Prezioso Samantha M. , Duong Duc M. , Kuiper Emily G. , Deng Qiudong , Albertí Sebastián , Conn Graeme L. , Goldberg Joanna B. 
Published: March 2019

AbstractThe Pseudomonas aeruginosa methyltransferase EftM trimethylates elongation factor-Tu (EF-Tu) on lysine 5 to form a post-translational modification important for initial bacterial adherence to host epithelial cells. EftM methyltransferase activity is directly temperature regulated. The protein stability of EftM is tuned with a melting temperature (Tm) around 37 °C such that the enzyme is stable and active at 25 °C, but is completely inactivated by protein unfolding at higher temperatures. This leads to higher observable levels of EF-Tu trimethylation at the lower temperature. Here we report an additional layer of thermoregulation resulting in lower eftM mRNA transcript level at 37 °C compared to 25 °C and show that this regulation occurs at the level of transcription initiation. To begin to define the impact of this system on P. aeruginosa physiology, we demonstrate that EF-Tu is the only observable substrate for EftM. Further, we interrogated the proteome of three different wild-type P. aeruginosa strains, their eftM mutants, and these mutants complemented with eftM and conclude that trimethylation of EF-Tu by EftM does not impact EF-Tu’s canonical function in translation. In addition to furthering our knowledge of this Pseudomonas virulence factor, this study provides an intriguing example of a protein with multiple layers of thermoregulation.