bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Notch output dynamics via specific E(spl)-HLH factors during bristle patterning in Drosophila
Authors: Couturier Lydie , Mazouni Khalil , Corson Francis , Schweisguth François 
Published: August 2019

AbstractThe stereotyped arrangement of sensory bristles on the adult fly thorax arises from a self-organized process, in which inhibitory Notch signaling both delimits proneural stripes and singles out sensory organ precursor cells (SOPs). A dynamic balance between proneural factors and Enhancer of split-HLH (E(spl)-HLH) Notch targets underlies patterning, but how this is regulated is unclear. Here, were identify two classes of E(spl)-HLH factors, whose expression both precedes and delimits proneural activity, and is dependent on proneural activity and required for proper SOP spacing within the stripes, respectively. These two classes are partially redundant, since a member of the second class, that is normally cross-repressed by members of the first class, can functionally compensate for their absence. The regulation of specific E(spl)-HLH genes by proneural factors amplifies the response to Notch as SOPs are being selected, contributing to patterning dynamics in the notum, and likely operates in other developmental contexts.
Linking in silico MS/MS spectra with chemistry data to improve identification of unknowns
Authors: McEachran Andrew D. , Balabin Ilya , Cathey Tommy , Transue Thomas R. , Al-Ghoul Hussein , Grulke Chris , Sobus Jon R. , Williams Antony J. 
Published: August 2019

AbstractConfident identification of unknown chemicals in high resolution mass spectrometry (HRMS) screening studies requires cohesive workflows and complementary data, tools, and software. Chemistry databases, screening libraries, and chemical metadata have become fixtures in identification workflows. To increase confidence in compound identifications, the use of structural fragmentation data collected via tandem mass spectrometry (MS/MS or MS2) is vital. However, the availability of empirically collected MS/MS data for identification of unknowns is limited. Researchers have therefore turned to in silico generation of MS/MS data for use in HRMS-based screening studies. This paper describes the generation en masse of predicted MS/MS spectra for the entirety of the US EPA’s DSSTox database using competitive fragmentation modelling and a freely available open source tool, CFM-ID. The generated dataset comprises predicted MS/MS spectra for ~700,000 structures, and mappings between predicted spectra, structures, associated substances, and chemical metadata. Together, these resources facilitate improved compound identifications in HRMS screening studies. These data are accessible via an SQL database, a comma-separated export file (.csv), and EPA’s CompTox Chemicals Dashboard.
TGF-β signaling promotes tube-structure-forming growth in pancreatic duct adenocarcinoma
Authors: Yamaguchi Takashi , Ikehara Sanae , Akimoto Yoshihiro , Nakanishi Hayao , Kume Masahiko , Yamamoto Kazuo , Ohara Osamu , Ikehara Yuzuru 
Published: August 2019

AbstractTube-forming growth is an essential histological feature of pancreatic duct adenocarcinoma (PDAC) and of the pancreatic duct epithelium; nevertheless, the nature of the signals that start to form the tubular structures remains unknown. Here, we showed the clonal growth of PDAC cell lines in a three-dimensional (3D) culture experiment that modeled the clonal growth of PDAC. At the beginning of this study, we isolated the sphere- and tube-forming clones from established mouse pancreatic cancer cell lines via limiting dilution culture using collagen gel. Compared with cells in spherical structures, the cells in the formed tubes exhibited a lower CK19 expression in 3D culture and in the tumor that grew in the abdominal cavity of nude mice. Conversely, the expression of the transforming growth factor β (TGF-β)-signaling target mRNAs was higher in the formed tube vs the spherical structures, suggesting that TGF-β signaling is more active in the tube-forming process than the sphere-forming process. Treatment of sphere-forming clones with TGF-β1 induced tube-forming growth, upregulated the TGF-β-signaling target mRNAs, and yielded electron microscopic findings of a fading epithelial phenotype. In contrast, the elimination of TGF-β-signaling activation by treatment with inhibitors diminished the tube-forming growth and suppressed the expression of the TGF-β-signaling target mRNAs. Moreover, upregulation of the Fn1, Mmp2, and Snai1 mRNAs, which are hallmarks of tube-forming growth in PDAC, was demonstrated in a mouse model of carcinogenesis showing rapid progression because of the aggressive invasion of tube-forming cancer. Our study suggests that the tube-forming growth of PDAC relies on the activation of TGF-β signaling and highlights the importance of the formation of tube structures.
Enhanced Depth Navigation Through Augmented Reality Depth Mapping in Patients with Low Vision
Authors: Angelopoulos Anastasios Nikolas , Ameri Hossein , Mitra Debbie , Humayun Mark 
Published: August 2019

AbstractPatients diagnosed with Retinitis Pigmentosa (RP) show, in the advanced stage of the disease, severely restricted peripheral vision causing poor mobility and decline in quality of life. This vision loss causes difficulty identifying obstacles and their relative distances. Thus, RP patients use mobility aids such as canes to navigate, especially in dark environments. A number of high-tech visual aids using virtual reality (VR) and sensory substitution have been developed to support or supplant traditional visual aids. These have not achieved widespread use because they are difficult to use or block off residual vision. This paper presents a unique depth to high-contrast pseudocolor mapping overlay developed and tested on a Microsoft Hololens 1 as a low vision aid for RP patients. A single-masked and randomized trial of the AR pseudocolor low vision aid to evaluate real world mobility and near obstacle avoidance was conducted consisting of 10 RP subjects. An FDA-validated functional obstacle course and a custom-made grasping setup were used. The use of the AR visual aid reduced collisions by 50% in mobility testing (p = 0.02), and by 70% in grasp testing (p = 0.03). This paper introduces a new technique, the pseudocolor wireframe, and reports the first significant statistics showing improvements for the population of RP patients with mobility and grasp.
Unstable, Super Critical CO2–Water Displacement in Fine Grained Porous Media under Geologic Carbon Sequestration Conditions
Authors: Gooya R. , Silvestri A. , Moaddel A. , Andersson M. P. , Stipp S. L. S. , Sørensen H. O. 
Published: August 2019

AbstractIn this study we investigated fluid displacement water with supercritical (sc) CO2 in chalk under conditions close to those used for geologic CO2 sequestration (GCS), to answer two main questions: How much volume is available for scCO2 injection? And what is the main mechanism of displacement over a range of temperatures? Characterization of immiscible scCO2 displacement, at the pore scale in the complex microstructure in chalk reservoirs, offers a pathway to better understand the macroscopic processes at the continuum scale. Fluid behavior was simulated by solving the Navier-Stokes equations, using finite-volume methods within a pore network. The pore network was extracted from a high resolution 3D image of chalk, obtained using X-ray nanotomography. Viscous fingering dominates scCO2 infiltration and pores remain only partially saturated. The unstable front, developed with high capillary number, causes filling of pores aligned with the flow direction, reaching a maximum of 70% scCO2 saturation. The saturation rate increases with temperature but the final saturation state is the same for all investigated temperatures. The higher the saturation rate, the higher the dynamic capillary pressure coefficient. A higher dynamic capillary pressure coefficient indicates that scCO2 needs more time to reach capillary equilibrium in the porous medium.
Metabolites of type I, II, III, and IV collagen may serve as markers of disease activity in axial spondyloarthritis
Authors: Hušáková Markéta , Bay-Jensen Anne-C. , Forejtová Šárka , Zegzulková Kateřina , Tomčík Michal , Gregová Monika , Bubová Kristýna , Hořínková Jana , Gatterová Jindra , Pavelka Karel , Siebuhr Anne Sofie 
Published: August 2019

AbstractLocal inflammation in axial spondyloarthritis (axSpA) leads to the release of collagen metabolites from the disease-affected tissue. We investigated whether collagen metabolites were associated with disease activity and could distinguish non-radiographic(nr)-axSpA from ankylosing spondylitis (AS). A total of 193 axSpA patients (nr-axSpA, n = 121 and AS, n = 72) and asymptomatic controls (n = 100) were included. Serum levels of metalloproteinase (MMP)-degraded collagen type I (C1M), type II (C2M), type III (C3M) and type IV (C4M2) were quantified by enzyme-linked immunosorbent assay (ELISA). All metabolites were higher in axSpA than in controls (all p < 0.001). Serum levels of C1M, C3M, and C4M2 were increased in AS compared to nr-axSpA (43.4 ng/mL vs. 34.6; p < 0.001, 15.4 vs. 12.8; p = 0.001, and 27.8 vs. 22.4; p < 0.001). The best metabolite to differentiate between axSpA and controls was C3M (AUC 0.95; specificity 92.0, sensitivity 83.4). C1M correlated with ASDAS-CRP in nr-axSpA (ρ = 0.37; p < 0.001) and AS (ρ = 0.57; p < 0.001). C1M, C3M, and C4M2 were associated with ASDAS-CRP in AS and nr-axSpA after adjustment for age, gender, and disease duration. Serum levels of collagen metabolites were significantly higher in AS and nr-axSpA than in controls. Moreover, the present study indicates that collagen metabolites reflect disease activity and are useful biomarkers of axSpA.
Chain length-dependent luminescence in acceptor-doped conjugated polymers
Authors: Scheer Pieter van der , Laar Ties van de , Sprakel Joris 
Published: August 2019

AbstractSemiconducting polymers doped with a minority fraction of energy transfer acceptors feature a sensitive coupling between chain conformation and fluorescence emission, that can be harnessed for advanced solution-based molecular sensing and diagnostics. While it is known that chain length strongly affects chain conformation, and its response to external cues, the effects of chain length on the emission patterns in chromophore-doped conjugated polymers remains incompletely understood. In this paper, we explore chain-length dependent emission in two different acceptor-doped polyfluorenes. We show how the binomial distribution of acceptor incorporation, during the probabilistic polycondensation reaction, creates a strong chain-length dependency in the optical properties of this class of luminescent polymers. In addition, we also find that the intrachain exciton migration rate is chain-length dependent, giving rise to additional complexity. Both effects combined, make for the need to develop sensoric conjugated polymers of improved monodispersity and chemical homogeneity, to improve the accuracy of conjugated polymer based diagnostic approaches.
Engineering genetically encoded FRET-based nanosensors for real time display of arsenic (As3+) dynamics in living cells
Authors: Soleja Neha , Manzoor Ovais , Khan Parvez , Mohsin Mohd. 
Published: August 2019

AbstractArsenic poisoning has been a major concern that causes severe toxicological damages. Therefore, intricate and inclusive understanding of arsenic flux rates is required to ascertain the cellular concentration and establish the carcinogenetic mechanism of this toxicant at real time. The lack of sufficiently sensitive sensing systems has hampered research in this area. In this study, we constructed a fluorescent resonance energy transfer (FRET)-based nanosensor, named SenALiB (Sensor for Arsenic Linked Blackfoot disease) which contains a metalloregulatory arsenic-binding protein (ArsR) as the As3+ sensing element inserted between the FRET pair enhanced cyan fluorescent protein (ECFP) and Venus. SenALiB takes advantage of the ratiometic FRET readout which measures arsenic with high specificity and selectivity. SenALiB offers rapid detection response, is stable to pH changes and provides highly accurate, real-time optical readout in cell-based assays. SenALiB-676n with a binding constant (Kd) of 0.676 × 10−6 M is the most efficient affinity mutant and can be a versatile tool for dynamic measurement of arsenic concentration in both prokaryotes and eukaryotes in vivo in a non-invasive manner.
Differential gene expression analysis reveals novel genes and pathways in pediatric septic shock patients
Authors: Mohammed Akram , Cui Yan , Mas Valeria R. , Kamaleswaran Rishikesan 
Published: August 2019

AbstractSeptic shock is a devastating health condition caused by uncontrolled sepsis. Advancements in high-throughput sequencing techniques have increased the number of potential genetic biomarkers under review. Multiple genetic markers and functional pathways play a part in development and progression of pediatric septic shock. We identified 53 differentially expressed pediatric septic shock biomarkers using gene expression data sampled from 181 patients admitted to the pediatric intensive care unit within the first 24 hours of their admission. The gene expression signatures showed discriminatory power between pediatric septic shock survivors and nonsurvivor types. Using functional enrichment analysis of differentially expressed genes, we validated the known genes and pathways in septic shock and identified the unexplored septic shock-related genes and functional groups. Differential gene expression analysis revealed the genes involved in the immune response, chemokine-mediated signaling, neutrophil chemotaxis, and chemokine activity and distinguished the septic shock survivor from non-survivor. The identification of the septic shock gene biomarkers may facilitate in septic shock diagnosis, treatment, and prognosis.
N-Substituted Auxiliaries for Aerobic Dehydrogenation of Tetrahydro-isoquinoline: A Theory-Guided Photo-Catalytic Design
Authors: Jayaraj Savithra , Badu-Tawiah Abraham K. 
Published: August 2019

AbstractVisible-light mediated aerobic dehydrogenation of N-heterocyclic compounds is a reaction with enormous potential for application. Herein, we report the first complete aerobic dehydrogenation pathway to large-scale production of isoquinolines. The discovery of this visible light photoredox reaction was enabled through the combination of mathematical simulations and real-time quantitative mass spectrometry screening. The theoretical calculations showed that hyper-conjugation, the main underlying factor hindering the aerobic oxidation of tetrahydroisoquinolines, is relieved both by π- and σ-donating substituents. This mechanistic insight provided a novel photocatalytic route based on N-substituted auxiliaries that facilitated the conversion of tetrahydroisoquinolines into the corresponding isoquinolines in just three simple steps (yield 71.7% in bulk-solution phase), using unmodified Ru(bpy)3Cl2 photocatalyst, sun energy, atmospheric O2, and at ambient temperature.
Independent effect of physical activity and resting heart rate on the incidence of atrial fibrillation in the general population
Authors: Choi Yeon Woo , Park Minsu , Lim Young-Hyo , Myung Jisun , Kim Byung Sik , Lee Yonggu , Shin Jeong-Hun , Park Hwan-Cheol , Shin Jinho , Kim Chun Ki , Park Jin-Kyu 
Published: August 2019

AbstractWhile physical activity (PA) may influence resting heart rate (RHR), and a low RHR may be a risk factor for atrial fibrillation (AF), controversy exists regarding the association between PA and development of AF. Using data from a Korean, prospective population cohort, we investigated the independent effect of PA and RHR on the incidence of AF in the general population. A total of 8,811 participants aged 40–69 years were analyzed. Total PA assessed based on questionnaires was divided into quartiles, with the lowest to the highest being Q1, Q2, Q3, and Q4. During a median follow-up of 139 months, AF developed in 167 participants (1.9%). Q3 of total PA was associated with a significantly lower risk of AF than Q1 even after adjusting for RHR as a covariate, but Q4 was not. The risk of AF was higher in participants with RHR < 60 bpm than in those with RHR 70–85 bpm, and the significance persisted after adjusting for PA as a covariate. This study showed that a moderate amount of total PA was associated with a lower risk of incident AF independent of RHR and that low RHR was an independent risk factor for AF in the general Korean population.
NOVA1 induction by inflammation and NOVA1 suppression by epigenetic regulation in head and neck squamous cell carcinoma
Authors: Kim Eun Kyung , Cho Yoon Ah , Seo Mi-kyoung , Ryu Hyunmi , Cho Byoung Chul , Koh Yoon Woo , Yoon Sun Och 
Published: August 2019

AbstractNeuro-oncological ventral antigen 1 (NOVA1) is known as a neuron-specific pre-mRNA binding splicing factor. Previously, it was shown to be highly upregulated in T lymphocytes, as well as fibroblasts/stromal spindle cells, in tertiary lymphoid tissues formed by the benign immune-inflammatory process, while it was frequently downregulated in tumor cells and other cells within the tumor microenvironment. Here, we sought to identify the mechanisms of NOVA1 modulation in head and neck squamous cell carcinoma (HNSCC). NOVA1 was induced by inflammatory-immune signals within the tumor microenvironment and was suppressed by epigenetic dysregulation, such as that with miR-146. We found attenuated expression of NOVA1 to be associated with non-oropharynx sites such as oral cavity, hypopharynx, and larynx, human papilloma virus (HPV)-negative SCC defined by immunohistochemistry for p16INK4a expression, fewer tumor infiltrating lymphocytes, and poor patient outcomes. Moreover, changes were discovered in epithelial mesenchymal transition-associated markers according to NOVA1 status. This study provides some insights to the underlying mechanism of NOVA1 regulation and suggests that NOVA1 may serve as a prognostic biomarker and potential therapeutic target for HNSCC in the future.
Effect of flavor on neuronal responses of the hypothalamus and ventral tegmental area
Authors: van Opstal A. M. , van den Berg-Huysmans A. A. , Hoeksma M. , Blonk C. , Pijl H. , Rombouts S. A. R. B. , van der Grond J. 
Published: August 2019

AbstractAlthough it is well known that food intake is affected by the palatability of food, the actual effect of flavoring on regulation of energy-homeostasis and reward perception by the brain, remains unclear. We investigated the effect of ethyl-butyrate (EB), a common non-caloric food flavoring, on the blood oxygen level dependent (BOLD) response in the hypothalamus (important in regulating energy homeostasis) and ventral tegmental area (VTA; important in reward processes). The 16 study participants (18–25 years, BMI 20–23 kg/m2) drank four study stimuli on separate visits using a crossover design during an fMRI setup in a randomized order. The stimuli were; plain water, water with EB, glucose solution (50gram/300 ml) and glucose solution with EB. BOLD responses to ingestion of the stimuli were determined in the hypothalamus and VTA as a measure of changes in neuronal activity after ingestion. In the hypothalamus and VTA, glucose had a significant effect on the BOLD response but EB flavoring did not. Glucose with and without EB led to similar decrease in hypothalamic BOLD response and glucose with EB resulted in a decrease in VTA BOLD response. Our results suggest that the changes in neuronal activity in the hypothalamus are mainly driven by energy ingestion and EB does not influence the hypothalamic response. Significant changes in VTA neuronal activity are elicited by energy combined with flavor.
A QSP Model for Predicting Clinical Responses to Monotherapy, Combination and Sequential Therapy Following CTLA-4, PD-1, and PD-L1 Checkpoint Blockade
Authors: Milberg Oleg , Gong Chang , Jafarnejad Mohammad , Bartelink Imke H. , Wang Bing , Vicini Paolo , Narwal Rajesh , Roskos Lorin , Popel Aleksander S. 
Published: August 2019

AbstractOver the past decade, several immunotherapies have been approved for the treatment of melanoma. The most prominent of these are the immune checkpoint inhibitors, which are antibodies that block the inhibitory effects on the immune system by checkpoint receptors, such as CTLA-4, PD-1 and PD-L1. Preclinically, blocking these receptors has led to increased activation and proliferation of effector cells following stimulation and antigen recognition, and subsequently, more effective elimination of cancer cells. Translation from preclinical to clinical outcomes in solid tumors has shown the existence of a wide diversity of individual patient responses, linked to several patient-specific parameters. We developed a quantitative systems pharmacology (QSP) model that looks at the mentioned checkpoint blockade therapies administered as mono-, combo- and sequential therapies, to show how different combinations of specific patient parameters defined within physiological ranges distinguish different types of virtual patient responders to these therapies for melanoma. Further validation by fitting and subsequent simulations of virtual clinical trials mimicking actual patient trials demonstrated that the model can capture a wide variety of tumor dynamics that are observed in the clinic and can predict median clinical responses. Our aim here is to present a QSP model for combination immunotherapy specific to melanoma.
Precision 500/√3 kV three‐stage VT with double excitation
Authors: Yin Xiaodong , Liu Hao , Lan Lei , Zhou Feng , Lei Min , Jiang Chunyang 
Published: August 2019

To develop the highest standard for high‐voltage ratio at power frequency, this study describes a three‐stage voltage transformer (VT) with high‐ and low‐voltage double excitation. In this high‐voltage VT, all primary windings are wound as a ‘pyramid’ structure, making it work at higher‐voltage possible. Moreover, the two high excitation and ratio coils are located as vertically symmetrical distribution, good for solving the insulation problem between two primary windings. On the basis of this scheme, a precision 500/√3 kV three‐stage VT has been developed. Calibration based on ‘series summation’ indicates that in the range of 20–120% rated voltage, the error of the three‐stage VT is as follows: (−17.2 to + 7.1) × 10−6 for the ratio error and −5.1 to −1.3 µrad for the phase error, which reaches accuracy class 0.002. Moreover, the uncertainty of this three‐stage VT is 8.7 × 10−6 for ratio and 8.7 µrad for phase (k = 2).
Sequence-dependent RNA helix conformational preferences predictably impact tertiary structure formation
Authors: Yesselman Joseph D. , Denny Sarah K. , Bisaria Namita , Herschlag Daniel , Greenleaf William J. , Das Rhiju 
Published: August 2019

SignificanceStructured RNAs fold into complex tertiary structures to perform critical roles in a multitude of biological functions. Over half the nucleotides in structured RNAs form simple Watson–Crick (WC) double helices, which can then assemble through non-WC interactions into elaborate tertiary structures. Here, we report the serendipitous discovery that sequence changes in WC base pairs impact the energetics of RNA tertiary folding. These observations led to a computational model for helix conformational fluctuations that then blindly predicted the results of thousands of high-throughput experiments with surprisingly high accuracy. Our study reveals that sequence-specific helix structure preferences are needed for understanding RNA folding quantitatively and outlines a route for dissecting the impact of helix conformational fluctuations across general RNA biophysical events.