bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-probing spectroscopy of XUV photo-ionization dynamics in atoms subjected to a strong-field environment
Authors: Azoury Doron , Krüger Michael , Orenstein Gal , Larsson Henrik R. , Bauch Sebastian , Bruner Barry D. , Dudovich Nirit 
Published: November 2017

AbstractSingle-photon ionization is one of the most fundamental light matter interactions in nature, serving as a universal probe of the quantum state of matter. By probing the emitted electron, one can decode the full dynamics of the interaction. When photo-ionization is evolving in the presence of a strong laser field, the fundamental properties of the mechanism can be signicantly altered. Here we demonstrate how the liberated electron can perform a self-probing measurement of such interaction with attosecond precision. Extreme ultraviolet attosecond pulses initiate an electron wavepacket by photo-ionization, a strong infrared field controls its motion, and finally electron–ion collision maps it into re-emission of attosecond radiation bursts. Our measurements resolve the internal clock provided by the self-probing mechanism, obtaining a direct insight into the build-up of photo-ionization in the presence of the strong laser field.
Quantification of flexoelectricity in PbTiO3/SrTiO3 superlattice polar vortices using machine learning and phase-field modeling
Authors: Li Q. , Nelson C. T. , Hsu S.-L. , Damodaran A. R. , Li L.-L. , Yadav A. K. , McCarter M. , Martin L. W. , Ramesh R. , Kalinin S. V. 
Published: November 2017

AbstractFlexoelectricity refers to electric polarization generated by heterogeneous mechanical strains, namely strain gradients, in materials of arbitrary crystal symmetries. Despite more than 50 years of work on this effect, an accurate identification of its coupling strength remains an experimental challenge for most materials, which impedes its wide recognition. Here, we show the presence of flexoelectricity in the recently discovered polar vortices in PbTiO3/SrTiO3 superlattices based on a combination of machine-learning analysis of the atomic-scale electron microscopy imaging data and phenomenological phase-field modeling. By scrutinizing the influence of flexocoupling on the global vortex structure, we match theory and experiment using computer vision methodologies to determine the flexoelectric coefficients for PbTiO3 and SrTiO3. Our findings highlight the inherent, nontrivial role of flexoelectricity in the generation of emergent complex polarization morphologies and demonstrate a viable approach to delineating this effect, conducive to the deeper exploration of both topics.
PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways
Authors: Naidu Srivatsava , Shi Lei , Magee Peter , Middleton Justin D. , Laganá Alessandro , Sahoo Sudhakar , Leong Hui Sun , Galvin Melanie , Frese Kristopher , Dive Caroline , Guzzardo Vincenza , Fassan Matteo , Garofalo Michela 
Published: November 2017

AbstractIn NSCLC alterations in PDGF receptors are markers of worst prognosis and efficient targeting of these receptors is yet to be achieved. In this study, we explored PDGFR-regulated microRNAs demonstrating that miR-23b cluster and miR-125a-5p are downregulated by increased expression of PDGFR-α or PDGFR-β in NSCLC cells. Mechanistically, the expression of these microRNAs is positively regulated by p53 and negatively modulated by NF-kB p65. Forced expression of miR-23b cluster or miR-125a-5p enhanced drug sensitivity and suppressed invasiveness of NSCLC cells by silencing several genes involved in oncogenic KRAS and NF-kB pathways, including SOS1, GRB2, IQGAP1, RALA, RAF-1, IKKβ, AKT2, ERK2 and KRAS itself. Of note, an inverse correlation between miR-23b cluster, miR-125a-5p and respective target genes was also found in vivo in a large dataset of lung adenocarcinoma samples. Furthermore, in vivo delivery of miR-23b cluster or miR-125a-5p significantly repressed tumour growth in a highly aggressive NSCLC circulating tumour cell (CTC) patient derived explant (CDX) mouse model. In conclusion, our finding sheds light on the PDGFR signaling and endorses the possibility to employ miR-23b cluster and miR-125a-5p as therapeutic tools to silence simultaneously a range of redundant pathways and main effectors of tumorigenesis in NSCLC.
Nitric oxide mediated inhibition of antigen presentation from DCs to CD4+ T cells in cancer and measurement of STAT1 nitration
Authors: Markowitz Joseph , Wang Jiang , Vangundy Zach , You Jia , Yildiz Vedat , Yu Lianbo , Foote Isaac P. , Branson Owen E. , Stiff Andrew R. , Brooks Taylor R. , Biesiadecki Brandon , Olencki Thomas , Tridandapani Susheela , Freitas Michael A. , Papenfuss Tracey , Phelps Mitch A. , Carson William E. 
Published: November 2017

AbstractMyeloid derived suppressor cells (MDSC) produce nitric oxide (NO) and inhibit dendritic cell (DC) immune responses in cancer. DCs present cancer cell antigens to CD4+T cells through Jak-STAT signal transduction. In this study, NO donors (SNAP and DETA-NONOate) inhibited DC antigen presentation. As expected, MDSC isolated from peripheral blood mononuclear cells (PBMC) from cancer patients produced high NO levels. We hypothesized that NO producing MDSC in tumor-bearing hosts would inhibit DC antigen presentation. Antigen presentation from DCs to CD4+T cells (T cell receptor transgenic OT-II) was measured via a [3H]-thymidine incorporation proliferation assay. MDSC from melanoma tumor models decreased the levels of proliferation more than pancreatic cancer derived MDSC. T cell proliferation was restored when MDSC were treated with inhibitors of inducible nitric oxide synthase (L-NAME and NCX-4016). A NO donor inhibited OT II T cell receptor recognition of OT II specific tetramers, thus serving as a direct measure of NO inhibition of antigen presentation. Our group has previously demonstrated that STAT1 nitration also mediates MDSC inhibitory effects on immune cells. Therefore, a novel liquid chromatography-tandem mass spectrometry assay demonstrated that nitration of the STAT1-Tyr701 occurs in PBMC derived from both pancreatic cancer and melanoma patients.
Disruption of diphthamide synthesis genes and resulting toxin resistance as a robust technology for quantifying and optimizing CRISPR/Cas9-mediated gene editing
Authors: Killian Tobias , Dickopf Steffen , Haas Alexander K. , Kirstenpfad Claudia , Mayer Klaus , Brinkmann Ulrich 
Published: November 2017

AbstractWe have devised an effective and robust method for the characterization of gene-editing events. The efficacy of editing-mediated mono- and bi-allelic gene inactivation and integration events is quantified based on colony counts. The combination of diphtheria toxin (DT) and puromycin (PM) selection enables analyses of 10,000–100,000 individual cells, assessing hundreds of clones with inactivated genes per experiment. Mono- and bi-allelic gene inactivation is differentiated by DT resistance, which occurs only upon bi-allelic inactivation. PM resistance indicates integration. The robustness and generalizability of the method were demonstrated by quantifying the frequency of gene inactivation and cassette integration under different editing approaches: CRISPR/Cas9-mediated complete inactivation was ~30–50-fold more frequent than cassette integration. Mono-allelic inactivation without integration occurred >100-fold more frequently than integration. Assessment of gRNA length confirmed 20mers to be most effective length for inactivation, while 16–18mers provided the highest overall integration efficacy. The overall efficacy was ~2-fold higher for CRISPR/Cas9 than for zinc-finger nuclease and was significantly increased upon modulation of non-homologous end joining or homology-directed repair. The frequencies and ratios of editing events were similar for two different DPH genes (independent of the target sequence or chromosomal location), which indicates that the optimization parameters identified with this method can be generalized.
Energy neutral: the human foot and ankle subsections combine to produce near zero net mechanical work during walking
Authors: Takahashi Kota Z. , Worster Kate , Bruening Dustin A. 
Published: November 2017

AbstractThe human foot and ankle system is equipped with structures that can produce mechanical work through elastic (e.g., Achilles tendon, plantar fascia) or viscoelastic (e.g., heel pad) mechanisms, or by active muscle contractions. Yet, quantifying the work distribution among various subsections of the foot and ankle can be difficult, in large part due to a lack of objective methods for partitioning the forces acting underneath the stance foot. In this study, we deconstructed the mechanical work production during barefoot walking in a segment-by-segment manner (hallux, forefoot, hindfoot, and shank). This was accomplished by isolating the forces acting within each foot segment through controlling the placement of the participants’ foot as it contacted a ground-mounted force platform. Combined with an analysis that incorporated non-rigid mechanics, we quantified the total work production distal to each of the four isolated segments. We found that various subsections within the foot and ankle showed disparate work distribution, particularly within structures distal to the hindfoot. When accounting for all sources of positive and negative work distal to the shank (i.e., ankle joint and all foot structures), these structures resembled an energy-neutral system that produced net mechanical work close to zero (−0.012 ± 0.054 J/kg).
A Complementary Scale of Biased Agonism for Agonists with Differing Maximal Responses
Authors: Burgueño Javier , Pujol Marta , Monroy Xavier , Roche David , Varela Maria Jose , Merlos Manuel , Giraldo Jesús 
Published: November 2017

AbstractCompelling data in the literature from the recent years leave no doubt about the pluridimensional nature of G protein-coupled receptor function and the fact that some ligands can couple with different efficacies to the multiple pathways that a receptor can signal through, a phenomenon most commonly known as functional selectivity or biased agonism. Nowadays, transduction coefficients (log(τ/KA)), based on the Black and Leff operational model of agonism, are widely used to calculate bias. Nevertheless, combining both affinity and efficacy in a single parameter can result in compounds showing a defined calculated bias of one pathway over other though displaying varying experimental bias preferences. In this paper, we present a novel scale (log(τ)), that attempts to give extra substance to different compound profiles in order to better classify compounds and quantify their bias. The efficacy-driven log(τ) scale is not proposed as an alternative to the affinity&efficacy-driven log(τ/KA) scale but as a complement in those situations where partial agonism is present. Both theoretical and practical approaches using μ-opioid receptor agonists are presented.
Oral exposure to dibutyl phthalate exacerbates chronic lymphocytic thyroiditis through oxidative stress in female Wistar rats
Authors: Wu Yang , Li Jinquan , Yan Biao , Zhu Yuqing , Liu Xudong , Chen Mingqing , Li Dai , Lee Ching-Chang , Yang Xu , Ma Ping 
Published: November 2017

AbstractChronic lymphocytic thyroiditis (CLT) is a common autoimmune disorder. The possible pathogenic role and mechanism of dibutyl phthalate (DBP) in CLT is still controversial. Experiments were conducted after 35-days of oral exposure to the three concentrations of DBP or saline, and three immunizations with thyroglobulin (TG). Healthy female Wistar rats were randomly divided into ten exposure groups (n = 8 each): (A) saline control, (B) 0.5 mg/kg/d DBP, (C) 5 mg/kg/d DBP, (D) 50 mg/kg/d DBP, (E) TG-immunized group, (F) TG- combined with 0.5 mg/kg/d DBP, (G) TG- combined with 5 mg/kg/d DBP, (H) TG- combined with 50 mg/kg/d DBP, (I) TG- combined with 50 mg/kg/d DBP plus 100 mg/kg/d vitamin C; (J) 100 mg/kg/d vitamin C. We showed that oral exposure DBP can aggravate CLT in rats. This deterioration was concomitant with increased thyroid auto antibodies, Th1/Th2 imbalance and Th17 immune response, activated pro-inflammatory and apoptosis pathways, and increased thyroid dysfunction in rats. Our results also suggested that DBP could promote oxidative damage. The study also found that vitamin C reduced the levels of oxidative stress and alleviated CLT. In short, the study showed that DBP exacerbated CLT through oxidative stress.
Microbial Diversity of Genital Ulcers of HSV-2 Seropositive Women
Authors: Mehta Supriya D. , Pradhan Ashish K. , Green Stefan J. , Naqib Ankur , Odoyo-June Elijah , Gaydos Charlotte A. , Barry Sheila , Landay Alan , Bailey Robert C. 
Published: November 2017

AbstractWe measured the microbial community structure of genital ulcers in women. Swabs from clinically detected ulcers were tested for HSV-2 and Treponema pallidum by polymerase chain reaction (PCR). HSV-2 and T. pallidum were detected by serum antibody testing. Microbial community structure was characterized by high-throughput 16 s rRNA gene amplicon sequencing. Multiple group testing and Elastic net and Lasso regressions identified taxa associated with differences in factors of interest. Among 49 ulcer specimens from 49 HSV-2 seropositive women, by PCR HSV-2 was recovered from 28 (57%) specimens and T. pallidum from none; one woman showed serologic evidence of syphilis. Overall, 63% of women were HIV-positive and 49% had an uncircumcised male sex partner. By both multiple group testing and regression, Porphyromonas (FDR p-value = 0.02), Prevotella (FDR p-value = 0.03), Anaerococcus (FDR p-value = 0.07), and Dialister (FDR p-value = 0.09) were detected at higher relative abundance in HSV-2 PCR-positive than negative ulcers. The presence of HSV-2 in a lesion was associated with presumed bacterial agents of Bacterial vaginosis. Differences in bacterial communities may contribute to HSV-2 ulcer pathogenesis, severity, or prolonged healing. If these results are confirmed, future studies may consider the influence of BV treatment on women’s GUD and HSV-2 incidence and recurrence.
Protein-Ligand Blind Docking Using QuickVina-W With Inter-Process Spatio-Temporal Integration
Authors: Hassan Nafisa M. , Alhossary Amr A. , Mu Yuguang , Kwoh Chee-Keong 
Published: November 2017

Abstract“Virtual Screening” is a common step of in silico drug design, where researchers screen a large library of small molecules (ligands) for interesting hits, in a process known as “Docking”. However, docking is a computationally intensive and time-consuming process, usually restricted to small size binding sites (pockets) and small number of interacting residues. When the target site is not known (blind docking), researchers split the docking box into multiple boxes, or repeat the search several times using different seeds, and then merge the results manually. Otherwise, the search time becomes impractically long. In this research, we studied the relation between the search progression and Average Sum of Proximity relative Frequencies (ASoF) of searching threads, which is closely related to the search speed and accuracy. A new inter-process spatio-temporal integration method is employed in Quick Vina 2, resulting in a new docking tool, QuickVina-W, a suitable tool for “blind docking”, (not limited in search space size or number of residues). QuickVina-W is faster than Quick Vina 2, yet better than AutoDock Vina. It should allow researchers to screen huge ligand libraries virtually, in practically short time and with high accuracy without the need to define a target pocket beforehand.
Impact of spatial characteristics in the left stenotic coronary artery on the hemodynamics and visualization of 3D replica models
Authors: Yang Yang , Liu Xin , Xia Yufa , Liu Xin , Wu Wanqing , Xiong Huahua , Zhang Heye , Xu Lin , Wong Kelvin K. L. , Ouyang Hanbin , Huang Wenhua 
Published: November 2017

AbstractCardiovascular disease has been the major cause of death worldwide. Although the initiation and progression mechanism of the atherosclerosis are similar, the stenotic characteristics and the corresponding medical decisions are different between individuals. In the present study, we performed anatomic and hemodynamic analysis on 8 left coronary arterial trees with 10 identified stenoses. A novel boundary condition method had been implemented for fast computational fluid dynamics simulations and patient-specific three-dimensional printed models had been built for visualizations. Our results suggested that the multiple spatial characteristics (curvature of the culprit vessel multiplied by an angle of the culprit’s vessel to the upstream parent branch) could be an index of hemodynamics significance (r = −0.673, P-value = 0.033). and reduction of the maximum velocity from stenosis to downstream was found correlated to the FFRCT (r = 0.480, p = 0.160). In addition, 3D printed models could provide accurate replicas of the patient-specific left coronary arterial trees compare to virtual 3D models (r = 0.987, P-value < 0.001). Therefore, the visualization of the 3D printed models could help understand the spatial distribution of the stenoses and the hand-held experience could potentially benefit the educating and preparing of medical strategies.
Fungal networks serve as novel ecological routes for enrichment and dissemination of antibiotic resistance genes as exhibited by microcosm experiments
Authors: Nazir Rashid , Shen Ju-Pei , Wang Jun-Tao , Hu Hang-Wei , He Ji-Zheng 
Published: November 2017

AbstractAntibiotic resistance genes (ARGs) in the environment and their subsequent acquisition by clinically important microorganisms are a serious concern. However, the spread of environmental ARGs remain largely unknown. We report, for the first time, the involvement of soil fungi in the distribution of bacteria with ARGs via soil microcosms. qPCR assay detected unique ARGs specifically found in the mycosphere of different fungi. Interestingly, the taxonomically and ecologically different fungi exerted different selection pressures on ARGs originating from the same source. Test fungi supported different antibiotic resistance bacteria enriched in the mycosphere and even transported to distant places. The relative abundance of the tnpA gene decreased, for manure, along mycelial networks of all fungi. While the fungal strain NFC-5 enriched the intI1 gene more, opposite to two other fungi at the migration front compared with the inoculation point for both sources. Such data indicate the differential effect of different fungi to facilitate horizontal gene transfer potential under fungal selection pressure. Our study provides the evidence that fungi can contribute ARGs, host bacterial diversity and abundance, and such interactive microbial consortia have the potential to disseminate the resistance determinants from one place to another, thus increasing the ARGs exposure risk to humans.
JMJD8 is a novel endoplasmic reticulum protein with a JmjC domain
Authors: Yeo Kok Siong , Tan Ming Cheang , Lim Yat-Yuen , Ea Chee-Kwee 
Published: November 2017

AbstractJumonji C (JmjC) domain-containing proteins have been shown to regulate cellular processes by hydroxylating or demethylating histone and non-histone targets. JMJD8 belongs to the JmjC domain-only family that was recently shown to be involved in angiogenesis and TNF-induced NF-κB signaling. Here, we employed bioinformatic analysis and immunofluorescence microscopy to examine the physiological properties of JMJD8. We demonstrated that JMJD8 localizes to the lumen of endoplasmic reticulum and that JMJD8 forms dimers or oligomers in vivo. Furthermore, we identified potential JMJD8-interacting proteins that are known to regulate protein complex assembly and protein folding. Taken together, this work demonstrates that JMJD8 is the first JmjC domain-containing protein found in the lumen of the endoplasmic reticulum that may function in protein complex assembly and protein folding.
Two-step process for disassembly mechanism of proteasome α7 homo-tetradecamer by α6 revealed by high-speed atomic force microscopy
Authors: Kozai Toshiya , Sekiguchi Taichiro , Satoh Tadashi , Yagi Hirokazu , Kato Koichi , Uchihashi Takayuki 
Published: November 2017

AbstractThe 20S proteasome is a core particle of the eukaryotic proteasome responsible for proteolysis and is composed of layered α and β hetero-heptameric rings. The α7 subunit, which is one of components of the α ring, is known to self-assemble into a double-ringed homo-tetradecamer composed of two layers of the α7 heptameric ring. The α7 tetradecamer is known to disassemble upon the addition of α6 subunit, producing a 1:7 hetero-octameric α6-α7 complex. However, the detailed disassembly mechanism remains unclear. Here, we applied high-speed atomic force microscopy (HS-AFM) to dissect the disassembly process of the α7 double ring caused by interaction with the α6. HS-AFM movies clearly demonstrated two different modes of interaction in which the α6 monomer initially cracks at the interface between the stacked two α7 single rings and the subsequent intercalation of the α6 monomer in the open pore of the α7 single ring blocks the re-association of the single rings into the double ring. This result provides a mechanistic insight about the disassembly process of non-native homo-oligomers formed by proteasome components which is crucial for the initial process for assembly of 20S proteasome.
Non-destructive elemental analysis of a carbonaceous chondrite with direct current Muon beam at MuSIC
Authors: Terada K. , Sato A. , Ninomiya K. , Kawashima Y. , Shimomura K. , Yoshida G. , Kawai Y. , Osawa T. , Tachibana S. 
Published: November 2017

AbstractElectron- or X-ray-induced characteristic X-ray analysis has been widely used to determine chemical compositions of materials in vast research fields. In recent years, analysis of characteristic X-rays from muonic atoms, in which a muon is captured, has attracted attention because both a muon beam and a muon-induced characteristic X-ray have high transmission abilities. Here we report the first non-destructive elemental analysis of a carbonaceous chondrite using one of the world-leading intense direct current muon beam source (MuSIC; MUon Science Innovative Channel). We successfully detected characteristic muonic X-rays of Mg, Si, Fe, O, S and C from Jbilet Winselwan CM chondrite, of which carbon content is about 2 wt%, and the obtained elemental abundance pattern was consistent with that of CM chondrites. Because of its high sensitivity to carbon, non-destructive elemental analysis with a muon beam can be a novel powerful tool to characterize future retuned samples from carbonaceous asteroids.
Large scale matching of function to the genetic identity of retinal ganglion cells
Authors: Pisano Filippo , Zampaglione Erin , McAlinden Niall , Roebber Jennifer , Dawson Martin D. , Mathieson Keith , Sher Alexander 
Published: November 2017

AbstractUnderstanding the role of neurons in encoding and transmitting information is a major goal in neuroscience. This requires insight on the data-rich neuronal spiking patterns combined, ideally, with morphology and genetic identity. Electrophysiologists have long experienced the trade-offs between anatomically-accurate single-cell recording techniques and high-density multi-cellular recording methods with poor anatomical correlations. In this study, we present a novel technique that combines large-scale micro-electrode array recordings with genetic identification and the anatomical location of the retinal ganglion cell soma. This was obtained through optogenetic stimulation and subsequent confocal imaging of genetically targeted retinal ganglion cell sub-populations in the mouse. With the many molecular options available for optogenetic gene expression, we view this method as a versatile tool for matching function to genetic classifications, which can be extended to include morphological information if the density of labelled cells is at the correct level.