bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal Variations in Scrubbing of Magmatic Gases at the Summit of Kīlauea Volcano, Hawai‘i
Authors: Hurwitz Shaul , Anderson Kyle R. 
Published: December 2019

AbstractMeasurements of gas compositions and emission rates play a major role in monitoring restless volcanoes. However, thermodynamic calculations imply that scrubbing by groundwater will prevent most HCl and significant SO2 emissions until dry pathways are established, thus leading to underestimates of gas released from magma and magma volumes. Despite the significance, direct evidence for scrubbing is mostly lacking. Based on 50 water samples collected between 2003 and 2011 from the deep NSF Well at the summit of Kīlauea Volcano, we show that the chemical and stable isotope compositions of groundwater were modified by magmatic gas condensation. Temporal variations of dissolved SO42− and Cl− in the water coincided with changes in magmatic and volcanic activities. The temporal variations in water level and chemical and isotopic compositions support prior inferences of magmatic SO2 and HCl scrubbing by groundwater at Kīlauea Volcano.
PROTACs: great opportunities for academia and industry
Authors: Sun Xiuyun , Gao Hongying , Yang Yiqing , He Ming , Wu Yue , Song Yugang , Tong Yan , Rao Yu 
Published: December 2019

AbstractAlthough many kinds of therapies are applied in the clinic, drug-resistance is a major and unavoidable problem. Another disturbing statistic is the limited number of drug targets, which are presently only 20–25% of all protein targets that are currently being studied. Moreover, the focus of current explorations of targets are their enzymatic functions, which ignores the functions from their scaffold moiety. As a promising and appealing technology, PROteolysis TArgeting Chimeras (PROTACs) have attracted great attention both from academia and industry for finding available approaches to solve the above problems. PROTACs regulate protein function by degrading target proteins instead of inhibiting them, providing more sensitivity to drug-resistant targets and a greater chance to affect the nonenzymatic functions. PROTACs have been proven to show better selectivity compared to classic inhibitors. PROTACs can be described as a chemical knockdown approach with rapidity and reversibility, which presents new and different biology compared to other gene editing tools by avoiding misinterpretations that arise from potential genetic compensation and/or spontaneous mutations. PRTOACs have been widely explored throughout the world and have outperformed not only in cancer diseases, but also in immune disorders, viral infections and neurodegenerative diseases. Although PROTACs present a very promising and powerful approach for crossing the hurdles of present drug discovery and tool development in biology, more efforts are needed to gain to get deeper insight into the efficacy and safety of PROTACs in the clinic. More target binders and more E3 ligases applicable for developing PROTACs are waiting for exploration.
Designing a multi-epitopic vaccine against the enterotoxigenic Bacteroides fragilis based on immunoinformatics approach
Authors: Majid Mahnoor , Andleeb Saadia 
Published: December 2019

AbstractEnterotoxigenic Bacteroides fragilis is an enteric pathogen which is described as a causative agent of various intestinal infections and inflammatory diseases. Moreover, various research studies have reported it to be a leading factor in the development of colorectal cancer. As a part of the normal human microbiome, its treatment has become quite a challenge due to the alarming resistance against the available antibiotics. Although, this particular strain of B. fragilis shows susceptibility to few antibiotics, it is pertinent to devise an effective vaccine strategy for its elimination. There is no vaccine available against this pathogen up to date; therefore, we systematically ventured the outer membrane toxin producing proteins found exclusively in the toxigenic B. fragilis through the in-silico approaches to predict a multi-epitopic chimeric vaccine construct. The designed protein constitutes of epitopes which are predicted for linear B cells, Helper and T cells of outer membrane proteins expected to be putative vaccine candidates. The finalized proteins are only expressed in the enterotoxigenic B. fragilis, thus proving them to be exclusive. The 3D structure of the protein was first predicted followed by its refinement and validation via utilizing the bioinformatic approaches. Docking of the designed protein with the TLR2 receptor forecasted apt binding. Upon immune simulation, notable levels were observed in the expression of the immune cells.
Altered visual feedback from an embodied avatar unconsciously influences movement amplitude and muscle activity
Authors: Bourdin Pierre , Martini Matteo , Sanchez-Vives Maria V. 
Published: December 2019

AbstractEvidence suggests that the sense of the position of our body parts can be surreptitiously deceived, for instance through illusory visual inputs. However, whether altered visual feedback during limb movement can induce substantial unconscious motor and muscular adjustments is not known. To address this question, we covertly manipulated virtual body movements in immersive virtual reality. Participants were instructed to flex their elbow to 90° while tensing an elastic band, as their virtual arm reproduced the same, a reduced (75°), or an amplified (105°) movement. We recorded muscle activity using electromyography, and assessed body ownership, agency and proprioception of the arm. Our results not only show that participants compensated for the avatar’s manipulated arm movement while being completely unaware of it, but also that it is possible to induce unconscious motor adaptations requiring significant changes in muscular activity. Altered visual feedback through body ownership illusions can influence motor performance in a process that bypasses awareness.
Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma
Authors: Cervenkova Lenka , Vycital Ondrej , Bruha Jan , Rosendorf Jachym , Palek Richard , Liska Vaclav , Daum Ondrej , Mohelnikova-Duchonova Beatrice , Soucek Pavel 
Published: December 2019

AbstractATP-binding cassette (ABC) and solute carrier (SLC) transporters translocate diverse substances across cellular membranes and their deregulation may cause drug resistance of cancers. This study investigated significance of protein expression and cellular localization of the previously suggested putative prognostic markers ABCC2 and SLC22A3 in pancreatic cancer patients. Protein localization and brush border staining intensity of ABCC2 and SLC22A3 was assessed in tumor tissue blocks of 65 pancreatic cancer patients and associated with clinical data and survival of patients with regard to therapy. Negative SLC22A3 brush border staining in pancreatic tumors significantly increased the risk of both disease progression and patient´s death in univariate analyses. Multivariate analyses confirmed the association of SLC22A3 expression with progression-free survival of patients. A subgroup analysis of patients treated with regimens based on nucleoside analogs suggested that patients with negative brush border staining or apical localization of SLC22A3 in tumor cells have worse overall survival. The combination of positive ABCC2 and negative SLC22A3 brush border staining predicted worst overall survival and patients with positive brush border staining of both proteins had best overall and progression-free survival. The present study shows for the first time that the protein presence and to some extent also localization of SLC22A3 significantly associate with prognosis of pancreatic cancer in both unstratified and chemotherapy-treated patients. The combination of ABCC2 and SLC22A3 brush border staining also needs further attention in this regard.
Mitragynine, an euphoric compound inhibits hERG1a/1b channel current and upregulates the complexation of hERG1a-Hsp90 in HEK293-hERG1a/1b cells
Authors: Tay Yea Lu , Amanah Azimah , Adenan Mohd Ilham , Wahab Habibah Abdul , Tan Mei Lan 
Published: December 2019

AbstractMitragyna speciosa Korth (M. speciosa) has been widely used as a recreational product, however, there are growing concerns on the abuse potentials and toxicity of the plant. Several poisoning and fatal cases involving kratom and mitragynine have been reported but the underlying causes remain unclear. The human ether-a-go-go-related gene 1 (hERG1) encodes the pore-forming subunit underlying cardiac rapidly delayed rectifier potassium current (IKr). Pharmacological blockade of the IKr can cause acquired long QT syndrome, leading to lethal cardiac arrhythmias. This study aims to elucidate the mechanisms of mitragynine-induced inhibition on hERG1a/1b current. Electrophysiology experiments were carried out using Port-a-Patch system. Quantitative RT-PCR, Western blot analysis, immunofluorescence and co-immunoprecipitation methods were used to determine the effects of mitragynine on hERG1a/1b expression and hERG1-cytosolic chaperones interaction. Mitragynine was found to inhibit the IKr current with an IC50 value of 332.70 nM. It causes a significant reduction of the fully-glycosylated (fg) hERG1a protein expression but upregulates both core-glycosylated (cg) expression and hERG1a-Hsp90 complexes, suggesting possible impaired hERG1a trafficking. In conclusion, mitragynine inhibits hERG1a/1b current through direct channel blockade at lower concentration, but at higher concentration, it upregulates the complexation of hERG1a-Hsp90 which may be inhibitory towards channel trafficking.
Normal red blood cells’ shape stabilized by membrane’s in-plane ordering
Authors: Mesarec L. , Góźdź W. , Iglič A. , Kralj-Iglič V. , Virga E. G. , Kralj S. 
Published: December 2019

AbstractRed blood cells (RBCs) are present in almost all vertebrates and their main function is to transport oxygen to the body tissues. RBCs’ shape plays a significant role in their functionality. In almost all mammals in normal conditions, RBCs adopt a disk-like (discocyte) shape, which optimizes their flow properties in vessels and capillaries. Experimentally measured values of the reduced volume (v) of stable discocyte shapes range in a relatively broad window between v ~ 0.58 and 0.8. However, these observations are not supported by existing theoretical membrane-shape models, which predict that discocytic RBC shape is stable only in a very narrow interval of v values, ranging between v ~ 0.59 and 0.65. In this study, we demonstrate that this interval is broadened if a membrane’s in-plane ordering is taken into account. We model RBC structures by using a hybrid Helfrich-Landau mesoscopic approach. We show that an extrinsic (deviatoric) curvature free energy term stabilizes the RBC discocyte shapes. In particular, we show on symmetry grounds that the role of extrinsic curvature is anomalously increased just below the nematic in-plane order-disorder phase transition temperature.
Developmental exposure to a mixture of perfluoroalkyl acids (PFAAs) affects the thyroid hormone system and the bursa of Fabricius in the chicken
Authors: Mattsson Anna , Sjöberg Sofia , Kärrman Anna , Brunström Björn 
Published: December 2019

AbstractPerfluoroalkyl acids (PFAAs) are ubiquitous environmental contaminants and eggs and nestlings of raptors and fish-eating birds often contain high levels of PFAAs. We studied developmental effects of a mixture of ten PFAAs by exposing chicken embryos to 0.5 or 3 μg/g egg of each compound in the mixture. Histological changes of the thyroid gland were noted at both doses and increased expression of mRNA coding for type III deiodinase was found at 0.5 μg/g egg. Serum concentrations of the free fraction of thyroid hormones (T3 and T4) were reduced by the PFAA mixture at 3 µg/g egg, which is in line with a decreased synthesis and increased turnover of thyroid hormones as indicated by our histological findings and the decreased mRNA expression of type III deiodinase. The relative weight of the bursa of Fabricius increased at a dose of 3 μg/g egg in females. The bursa is the site of B-cell development in birds and is crucial for the avian adaptive immune system. Analysis of plasma and liver concentrations of the mixture components showed differences depending on chain length and functional group. Our results highlight the vulnerability of the thyroid hormone and immune systems to PFAAs.
Laser-Driven Modulation of Electron Beams in a Dielectric Micro-Structure for X-Ray Free-Electron Lasers
Authors: Hermann Benedikt , Bettoni Simona , Egenolf Thilo , Niedermayer Uwe , Prat Eduard , Ischebeck Rasmus 
Published: December 2019

AbstractWe describe an application of laser-driven modulation in a dielectric micro-structure for the electron beam in a free-electron laser (FEL). The energy modulation is transferred into longitudinal bunching via compression in a magnetic chicane before entering the undulator section of the FEL. The bunched electron beam comprises a series of enhanced current spikes separated by the wavelength of the modulating laser. For beam parameters of SwissFEL at a total bunch charge of 30 pC, the individual spikes are expected to be as short as 140 as (FWHM) with peak currents exceeding 4 kA. The proposed modulation scheme requires the electron beam to be focused into the micrometer scale aperture of the dielectric structure, which imposes strict emittance and charge limitations, but, due to the small interaction region, the scheme is expected to require ten times less laser power as compared to laser modulation in a wiggler magnet, which is the conventional approach to create a pulse train in FELs.
Random nanohole arrays and its application to crystalline Si thin foils produced by proton induced exfoliation for solar cells
Authors: Lee Hyeon-Seung , Choi Jae Myeong , Jung Beomsic , Kim Joonkon , Song Jonghan , Jeong Doo Seok , Park Jong-Keuk , Kim Won Mok , Lee Doh-Kwon , Lee Taek Sung , Lee Wook Seong , Lee Kyeong-Seok , Ju Byeong-Kwon , Kim Inho 
Published: December 2019

AbstractWe report high efficiency cell processing technologies for the ultra-thin Si solar cells based on crystalline Si thin foils (below a 50 µm thickness) produced by the proton implant exfoliation (PIE) technique. Shallow textures of submicrometer scale is essential for effective light trapping in crystalline Si thin foil based solar cells. In this study, we report the fabrication process of random Si nanohole arrays of ellipsoids by a facile way using low melting point metal nanoparticles of indium which were vacuum-deposited and dewetted spontaneously at room temperature. Combination of dry and wet etch processes with indium nanoparticles as etch masks enables the fabrication of random Si nanohole arrays of an ellipsoidal shape. The optimized etching processes led to effective light trapping nanostructures comparable to conventional micro-pyramids. We also developed the laser fired contact (LFC) process especially suitable for crystalline Si thin foil based PERC solar cells. The laser processing parameters were optimized to obtain a shallow LFC contact in conjunction with a low contact resistance. Lastly, we applied the random Si nanohole arrays and the LFC process to the crystalline Si thin foils (a 48 µm thickness) produced by the PIE technique and achieved the best efficiency of 17.1% while the planar PERC solar cell without the Si nanohole arrays exhibit 15.6%. Also, we demonstrate the ultra-thin wafer is bendable to have a 16 mm critical bending radius.
No metagenomic evidence of tumorigenic viruses in cancers from a selected cohort of immunosuppressed subjects
Authors: Passaro Nunzia , Casagrande Andrea , Chiara Matteo , Fosso Bruno , Manzari Caterina , D’Erchia Anna Maria , Iesari Samuele , Pisani Francesco , Famulari Antonio , Tulissi Patrizia , Mastrosimone Stefania , Maresca Maria Cristina , Mercante Giuseppe , Spriano Giuseppe , Corrado Giacomo , Vizza Enrico , Garbuglia Anna Rosa , Capobianchi Maria Rosaria , Mottini Carla , Cenci Alessandra , Tartaglia Marco , Costa Alessandro Nanni , Pesole Graziano , Crescenzi Marco 
Published: December 2019

AbstractThe possible existence of yet undiscovered human tumorigenic viruses is still under scrutiny. The development of large-scale sequencing technologies, coupled with bioinformatics techniques for the characterization of metagenomic sequences, have provided an invaluable tool for the detection of unknown, infectious, tumorigenic agents, as demonstrated by several recent studies. However, discoveries of novel viruses possibly associated with tumorigenesis are scarce at best. Here, we apply a rigorous bioinformatics workflow to investigate in depth tumor metagenomes from a small but carefully selected cohort of immunosuppressed patients. While a variegated bacterial microbiome was associated with each tumor, no evidence of the presence of putative oncoviruses was found. These results are consistent with the major findings of several recent papers and suggest that new human tumorigenic viruses are not common even in immunosuppressed populations.
Collagen fragments quantified in serum as measures of desmoplasia associate with survival outcome in patients with advanced pancreatic cancer
Authors: Willumsen Nicholas , Ali Suhail M. , Leitzel Kim , Drabick Joseph J. , Yee Nelson , Polimera Hyma V. , Nagabhairu Vinod , Krecko Laura , Ali Ayesha , Maddukuri Ashok , Moku Prashanth , Ali Aamnah , Poulose Joyson , Menon Harry , Pancholy Neha , Costa Luis , Karsdal Morten A. , Lipton Allan 
Published: December 2019

AbstractPancreatic ductal adenocarcinoma (PDAC) patients have poor prognosis and poor response to treatment. This is largely due to PDAC being associated with a dense and active stroma and tumor fibrosis (desmoplasia). Desmoplasia is characterized by excessive degradation and formation of the extracellular matrix (ECM) generating collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in pre-treatment serum with outcome in patients with PDAC. Matrix metalloprotease (MMP)-degraded type I collagen (C1M), type III collagen (C3M), type IV collagen (C4M) and a pro-peptide of type III collagen (PRO-C3) were measured by ELISA in pre-treatment serum from a randomized phase 3 clinical trial of patients with stage III/IV PDAC treated with 5-fluorouracil based therapy (n = 176). The collagen fragments were evaluated for their correlation (r, Spearman) with serum CA19-9 and for their association with overall survival (OS) based on Cox-regression analyses. In this phase 3 PDAC trial, pre-treatment serum collagen fragment levels were above the reference range for 67%-98% of patients, with median values in PDAC approximately two-fold higher than reference levels. Collagen fragment levels did not correlate with CA19-9 (r = 0.049–0.141,p = ns). On a continuous basis, higher levels of all collagen fragments were associated with significantly shorter OS. When evaluating degradation (C3M) and formation (PRO-C3) of type III collagen further, higher PRO-C3 was associated with poor OS (>25thpercentile cut-point, HR = 2.01, 95%CI = 1.33–3.05) and higher C3M/PRO-C3 ratio was associated with improved OS (>25thpercentile cut-point, HR = 0.53, 95%CI = 0.34–0.80). When adjusting for CA19–9 and clinical covariates, PRO-C3 remained significant (HR = 1.65, 95%CI = 1.09–2.48). In conclusion, collagen remodeling quantified in pre-treatment serum as a surrogate measure of desmoplasia was significantly associated with OS in a phase 3 clinical PDAC trial, supporting the link between desmoplasia, tumorigenesis, and response to treatment. If validated, these biomarkers may have prognostic and/or predictive potential in future PDAC trials.
MicroRNA-548 regulates high mobility group box 1 expression in patients with preterm birth and chorioamnionitis
Authors: Son Ga-Hyun , Kim Youngmi , Lee Jae Jun , Lee Keun-Young , Ham Heejin , Song Ji-Eun , Park Sung Taek , Kim Young-Han 
Published: December 2019

AbstractHigh mobility group box 1 (HMGB1) is a prototypic alarmin and plays an important role in the pathogenesis of inflammatory process in spontaneous preterm birth. This study was conducted to compare the levels of HMGB1 in amniotic fluid and amnion membranes in women with chorioamnionitis/intra-amniotic inflammation to the levels in healthy controls. We also aimed to elucidate the involvement of microRNA-548 (miR-548) in regulating HMGB1 expression and its function in human amniotic epithelial cells (hAECs). A bioinformatics analysis predicted the binding of HMGB1 by the miR-548 cluster. A repressed and forced expression assay in hAECs was performed to investigate the causal relationship between the miR-548 cluster and HMGB1. The levels of HMGB1 in amniotic fluid and amnion membranes were significantly higher in patients with intra-amniotic inflammation/chorioamnionitis than in those without inflammation. The miR-548 was significantly under-expressed in amnion membranes from patients with chorioamnionitis than in normal term controls. Repressed expression of miR-548 up-regulated HMGB1 expression in hAECs and increased its release from hAECs. Moreover, forced expression of miR-548 suppressed HMGB1 and inflammatory cytokines in hAECs, which increased when treated with lipopolysaccharide. These results suggest miR-548 can alter the inflammatory responses in hAECs, and might be involved in the pathogenesis of preterm birth by regulating HMGB1.
Crystal structure, Hirshfeld surface analysis and DFT studies of 5-(adamantan-1-yl)-3-[(4-chlorobenzyl)sulfanyl]-4-methyl-4H-1,2,4-triazole, a potential 11β-HSD1 inhibitor
Authors: Al-Wahaibi Lamya H. , Joubert Jacques , Blacque Olivier , Al-Shaalan Nora H. , El-Emam Ali A. 
Published: December 2019

Abstract5-(Adamantan-1-yl)-3-[(4-chlorobenzyl)sulfanyl]-4-methyl-4H-1,2,4-triazole (4) was identified as a potential 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor and this paper describes the in-depth structural analysis thereof. Compound 4 was synthesized in a 92% yield and its 3D-structure confirmed by single-crystal X-ray diffraction. Hirshfeld surface analysis indicated that H…H, C-H…C, C-H…Cl and especially C-H…N hydrogen bond interactions are the primary contributors to the intermolecular stabilisation in the crystal. In order to explore the properties of 4, free from the influence of the crystal field, density functional theory (DFT) calculations were conducted. Results indicated that the DFT optimized geometry of 4 produced a conformer (4a) that is significantly different from the crystal structure. Further experiments confirmed that the crystal structure is not the absolute minimum conformation. This indicated that the crystal packing forces has significantly influenced the conformation thereof. Frontier molecular orbital energies and net atomic charges were also calculated to elucidate the electronic properties of 4a. These results provided insight into areas of the molecule that may present with the ability to form binding interactions at the 11β-HSD1 active site. Molecular docking experiments revealed important intermolecular interactions between 4a and 11β-HSD1. These results indicate that 4 may be considered for further drug design endeavors.