bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure of yeast xylose reductase in complex with a novel NADP‐DTT adduct provides insights into substrate recognition and catalysis
Authors: Paidimuddala Bhaskar , Mohapatra Samar B. , Gummadi Sathyanarayana N. , Manoj Narayanan 
Published: September 2018

Aldose reductases (ARs) belonging to the aldo‐keto reductase (AKR) superfamily catalyze the conversion of carbonyl substrates into their respective alcohols. Here we report the crystal structures of the yeast Debaryomyces nepalensis xylose reductase (DnXR, AKR2B10) in the apo form and as a ternary complex with a novel NADP‐DTT adduct. Xylose reductase, a key enzyme in the conversion of xylose to xylitol, has several industrial applications. The enzyme displayed the highest catalytic efficiency for l‐threose (138 ± 7 mm−1·s−1) followed by d‐erythrose (30 ± 3 mm−1·s−1). The crystal structure of the complex reveals a covalent linkage between the C4N atom of the nicotinamide ring of the cosubstrate and the S1 sulfur atom of DTT and provides the first structural evidence for a protein mediated NADP–low‐molecular‐mass thiol adduct. We hypothesize that the formation of the adduct is facilitated by an in‐crystallo Michael addition of the DTT thiolate to the specific conformation of bound NADPH in the active site of DnXR. The interactions between DTT, a four‐carbon sugar alcohol analog, and the enzyme are representative of a near‐cognate product ternary complex and provide significant insights into the structural basis of aldose binding and specificity and the catalytic mechanism of ARs.DatabaseStructural data are available in the PDB under the accession numbers 5ZCI and 5ZCM.
Off‐Mount Calibration and One New Potential Pyrrhotite Reference Material for Sulfur Isotope Measurement by Secondary Ion Mass Spectrometry
Authors: Li Rucao , Xia Xiaoping , Yang Shenghong , Chen Huayong , Yang Qing 
Published: September 2018

Sulfur isotope measurements in three sulfide (two pyrite and one pyrrhotite) samples on two epoxy mounts showed that the mount‐to‐mount variation of raw δ34S values was negligible when secondary ion mass spectrometry (SIMS) analytical settings remained stable. In consequence, an off‐mount calibration procedure for SIMS sulfur isotope analysis was applied in this study. YP136 is a pyrrhotite sample collected from northern Finland. Examination of thin sections with a polarising microscope, backscattered electron image analyses and wavelength dispersive spectrometry mapping showed that the sample grains display no internal growth or other zoning. A total of 318 sulfur isotope (spot) measurements conducted on more than 100 randomly selected grains yielded highly consistent sulfur isotope ratios. The repeatability of all the analytical results of 34S/32S was 0.3‰ (2s, n = 318), which is the same as that of the well‐characterised pyrite reference materials PPP‐1 and UWPy‐1. Its δ34S value determined by gas mass spectrometry was 1.5 ± 0.1‰ (2s, n = 11), which agrees with the SIMS data (1.5 ± 0.3‰, 2s) calibrated by pyrrhotite reference material Po‐10. Therefore, YP136 pyrrhotite is considered a candidate reference material for in situ sulfur isotope determination.
Experimental investigation of mechanical, thermal, and ablation performance of ZrO2/SiC modified C‐Ph composites
Authors: Subha Sivakumar , Singh Dalbir , Venkatanarayanan Pappakudi Srinivasan , Kavitha Narayanan 
Published: September 2018

AbstractIn this study, an effort has been made to improve the mechanical, thermal, and ablation performance of carbon‐phenolic (C‐Ph) composites. The ZrO2, SiC, and ZrO2/SiC hybrid fillers were synthesized using sol‐gel method followed by individual incorporation into C‐Ph composites. The thermal stability and flexural strength of these C‐Ph composites were analyzed using thermogravimetry analysis and three‐point bending test, respectively. A significant improvement in the flexural strength and modulus of the reinforced C‐Ph composites was observed and also exhibited the higher thermal stability. The oxyacetylene flame test was conducted to measure the ablation behavior of these filler reinforced C‐Ph composites under a heat flux of 4.0 MW/m2 for 60 seconds. ZrO2/SiC0.5 reinforcement in the C‐Ph composite decreased the linear and mass ablation rates by 46% and 22%, respectively when compared with pure C‐Ph composite. The surface morphology analysis revealed that the burnt composite covered with the ZrC ceramic phase and SiO2 bubble‐like structure, which could have improved the ablation resistance of composites. These results were found well within the acceptable range when using the surface energy dispersive spectroscopy and X‐ray diffraction analysis.
Aligned continuous cylindrical pores derived from electrospun polymer fibers in titanium diboride
Authors: Hicks David Cyprian , Zhou Zhengping , Liu Guoliang , Tallon Carolina 
Published: September 2018

AbstractThe use of electrospun polystyrene (PS) fibers to create continuous long range ordered multi‐scale porous structures in titanium diboride (TiB2) is investigated in this work. The introduction of electrospunPSfibers as a sacrificial filler into a colloidal suspension of TiB2allows for easy control over the pore size, porosity, and long range ordering of the porous structures of the sintered ceramics. Green bodies were formed by vacuum infiltrating an electrospun‐fiber‐filled mold with the colloidal TiB2suspension. The size, volume, distribution, and dispersion of the pores were optimized by carefully selecting the sacrificial polymer, the fiber diameter, the solvent, and the solid content of TiB2. The green bodies were partially sintered at 2000°C to form a multi‐scale porous structureviathe removal of thePSfibers. Aligned continuous cylindrical pores homogeneously distributed across the samples were derived from thePSfibers in a range of ~5‐20 μm and partial sintering produced inter‐particle porosity with sizes of ~0.3‐1 μm. TiB2near‐net‐shaped parts with the multi‐scale porosities (~50‐70%) were successfully cast and sintered. This low‐cost processing technique can be used in the production of thermally and mechanically anisotropic structures into near‐net shape parts, for extreme environment applications, such as high temperature insulation.
Survival analysis and development of a prognostic nomogram for bone‐metastatic prostate cancer patients: A single‐center experience in Indonesia
Authors: Afriansyah Andika , Hamid Agus Rizal AH , Mochtar Chaidir A , Umbas Rainy 
Published: September 2018

ObjectivesTo analyze predictive clinical factors of survival in bone‐metastatic prostate cancer, and to develop a prognostic nomogram for patients with this condition.MethodsThe present study included 392 patients with bone‐metastatic prostate cancer treated with androgen deprivation therapy. Pretreatment parameters were analyzed using the Cox proportional hazards model to identify the predictors of overall survival. Covariates – which showed statistical significance on multivariate analysis – were used to develop a nomogram. A linear predictor model was utilized to develop the nomogram.ResultsThe median overall survival was 40.3 months (95% confidence interval 32.2–48.5). Univariate analysis showed that clinical T stage, Gleason score, initial prostate‐specific antigen value and the number of metastatic lesions were independent prognostic factors for overall survival. These predictors remained significant as independent prognostic factors for overall survival after analysis using the multivariate Cox regression model. The nomogram constructed from those prognostic factors showed good discrimination for predicting the 5‐year overall survival, with an area under the curve of 0.69. Acceptable agreement of the observed and predicted probabilities was observed in the calibration plot.ConclusionsThe present prognostic nomogram might be a useful tool for predicting overall survival in pretreatment bone‐metastatic prostate cancer, specifically among Indonesian patients. Further studies are required to provide external validation to support the utilization of this nomogram.
Chemical interaction of D9 alloy clad with B4C in liquid sodium: Studies employing XPS, XRD, and SEM
Authors: Chandran Kannan , Clinsha Pollayil Claxton , Lavanya Mani , Anthonysamy Savari , Gnanasekar Kovilpillai Immanuvel 
Published: September 2018

AbstractA cell representing typical control rod subassembly of the prototype fast breeder reactor is designed to probe the liquid sodium‐mediated chemical interaction of boron carbide (B4C) control rod with the D9 alloy clad. The cell was equilibrated at 973 K for 5000 hours with liquid sodium in the annular gap. XRD shows the formation of Cr3C2 and Fe2B along with oxides of Ni, Cr, and Fe. XPS studies reveal the diffusion of boron and carbon up to a depth of about 160 and 120 μm, respectively. A boron‐rich region is observed up to a depth of about 40 μm which consists of B3+ arising from oxides and a nearly constant elemental boron region, extending up to a depth of 160 μm. The highly reacted zone extends up to a depth of about 40 μm consisting of oxides of most of the elements of D9 clad exhibiting a higher valence states. As the cell is helium leak tested, oxygen out gassed from B4C at 973 K played a major role in chemical oxidation of the constituents of the D9 alloy which can be minimized by using high‐density B4C.
The histone deacetylase inhibitor nicotinamide exacerbates neurodegeneration in the lactacystin rat model of Parkinson's disease
Authors: Harrison Ian F. , Powell Nicholas M. , Dexter David T. 
Published: September 2018

AbstractHistone hypoacetylation is associated with dopaminergic neurodegeneration in Parkinson's disease (PD), because of an imbalance in the activities of the enzymes responsible for histone (de)acetylation. Correction of this imbalance, with histone deacetylase (HDAC) inhibiting agents, could be neuroprotective. We therefore hypothesize that nicotinamide, being a selective inhibitor of HDAC class III as well as having modulatory effects on mitochondrial energy metabolism, would be neuroprotective in the lactacystin rat model of PD, which recapitulates the formation of neurotoxic accumulation of altered proteins within the substantia nigra to cause progressive dopaminergic cell death. Rats received nicotinamide for 28 days, starting 7 days after unilateral injection of the irreversible proteasome inhibitor, lactacystin, into the substantia nigra. Longitudinal motor behavioural testing and structural magnetic resonance imaging were used to track changes in this model of PD, and assessment of nigrostriatal integrity, histone acetylation and brain gene expression changes post‐mortem used to quantify nicotinamide‐induced neuroprotection. Counterintuitively, nicotinamide dose‐dependently exacerbated neurodegeneration of dopaminergic neurons, behavioural deficits and structural brain changes in the lactacystin‐lesioned rat. Nicotinamide treatment induced histone hyperacetylation and over‐expression of numerous neurotrophic and anti‐apoptotic factors in the brain, yet failed to result in neuroprotection, rather exacerbated dopaminergic pathology. These findings highlight the importance of inhibitor specificity within HDAC isoforms for therapeutic efficacy in PD, demonstrating the contrasting effects of HDAC class III inhibition upon cell survival in this animal model of the disease.Open science badgesThis article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
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The crosstalk between glycosphingolipids and neural stem cells
Authors: Bottai Daniele , Adami Raffaella , Ghidoni Riccardo 
Published: September 2018

AbstractUntil a few years ago, the majority of cell functions were envisioned as the result of protein and DNA activity. The cell membranes were considered as a mere structure of support and/or separation. In the last years, the function of cell membranes has, however, received more attention and their components of lipid nature have also been depicted as important cell mediators and the membrane organization was described as an important determinant for membrane‐anchored proteins activity. In particular, because of their high diversity, glycosphingolipids offer a wide possibility of regulation. Specifically, the role of glycosphingolipids, in the fine‐tuning of neuron activity, has recently received deep attention. For their pivotal role in vertebrate and mammals neural development, neural stem cells regulation is of main interest especially concerning their further functions in neurological pathology progression and treatment. Glycosphingolipids expression present a developmental regulation. In this view, glycosphingolipids can hold an important role in neural stem cells features because of their heterogeneity and their consequent capacity for eclectic interaction with other cell components.
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JQ1 and PI3K inhibition synergistically reduce salivary adenoid cystic carcinoma malignancy by targeting the c‐Myc and EGFR signaling pathways
Authors: Liu Xiaojing , Wu Haitao , Huang Ping , Zhang Fenghe 
Published: September 2018

BackgroundTo investigate the therapeutic mechanism of the BRD4 inhibitor JQ1 in SACC‐83 cells and explore strategies to enhance its therapeutic potential.Material and MethodsSACC‐83 cells were used in the experiment. Immunohistochemistry was used to assess BRD4 expression in SACC tissues and corresponding adjacent non‐tumor tissues. Cell viability and proliferation were evaluated using the Cell Counting Kit‐8 assay. Flow cytometry was used to quantitate apoptosis. Levels of cleaved caspase‐3, BRD4, c‐Myc, pEGFR (γ‐1173), and EGFR were determined by quantitative real‐time PCR and Western blot. To study the role of EGFR in JQ1 resistance, we generated EGFR knockdown SACC‐83 cells by siRNA transfection.ResultsOur study revealed that BRD4 was overexpressed and could be a treatment target in SACC. The BRD4 inhibitor JQ1 markedly inhibited c‐Myc expression in SACC‐83 cells, which produced modest therapeutic effects. Nevertheless, the EGFR pathway was strongly activated following JQ1 treatment, which led to JQ1 resistance. Combined JQ1 and PI3K inhibitor treatment effectively increased the therapeutic potential by inhibiting the EGFR and c‐Myc signaling pathways in SACC‐83 cells. Moreover, EGFR knockdown sensitized SACC‐83 cells to JQ1.ConclusionThese data demonstrate that EGFR and c‐Myc signaling synergistically drive SACC progression. The JQ1 and PI3K inhibitor combination exhibited a strong synergistic effect by suppressing c‐Myc and EGFR in SACC‐83 cells, identifying a novel rational combinatorial treatment. Moreover, EGFR expression influences the sensitivity of SACC‐83 cells to JQ1, which is useful for planning treatment.
Introduction to Focus Issue on Laudato Si'
Authors: Jenkins Willis 
Published: September 2018

AbstractThe encyclical Laudato si’ can be read as a religious ethic in several different ways. Contributors to this focus issue read it as magisterial teaching, as environmental thought, as Global South criticism, as Latinx theology, and as philosophy of religion. Foregrounding South American and Latinx receptions, the cumulative argument of this focus issue is that LS represents a cultural event that invites interpretations from contexts and disciplines beyond North Atlantic theological ethics.
Laudato Si’: Care for Creation at the Center of a New Social Issue
Authors: Blanco Pablo A. 
Published: September 2018

AbstractThis essay reviews the documents of the pontifical magisterium of the Church from the encyclical Mater et magistra () to the exhortation Evangelii gaudium (2013), in order to show the Church’s historical commitment to the defense of the environment. It then argues that Laudato si’ elevates the theological status of the environmental crisis to that of a new social issue, much as Leo XIII did for the industrial crisis with his encyclical letter Rerum novarum ().
“Our Sister, Mother Earth”: Solidarity and Familial Ecology in Laudato Si’
Authors: Flores Nichole M. 
Published: September 2018

AbstractLaudato si’, with its articulation of a familial ecology reflecting Francis’s Latin American context, expands the subject of solidarity in Catholic social teaching and thought. Yet, this ecological vision of family fails to attend to the problem of gender subordination latent in Catholic social teaching, including in its approaches to ecology. A vision of solidarity that eradicates gender and ecological subordination must elaborate a familial ecology characterized by both mercy and equality.
Let Black People Be: A Plea for Racial Specificity in the Afterlife of Africanized Slavery
Authors: Grimes Katie 
Published: September 2018

AbstractThis article introduces a new term, “anti‐blackness supremacy,” in order to supplement existing theological discourse about the ethical life of racism. To a much greater extent than the terms “racism, ” “white privilege” or even “white supremacy,” this term also better positions scholars to address what I identify as the two most pressing problems in anti‐racist discourse: first, the inability to diagnose the relation between classism and racism without reducing one into the other; and second, the tendency to treat racism as a monolithic evil that falls upon all people of color equally and in the same way. The former error has distorted political discourse for decades; the latter misconception intensifies as the United States undergoes demographic shifts in the wake of immigration from Asia, Latin America, and Africa. Both of these errors arise from a pervasive misunderstanding of the slave regime that has set our current racial system in motion. In truth, slavery primarily represents not a mechanism of profit extraction, but a relation of a unique type of power. The term “anti‐blackness supremacy,” I contend, corrects both of these misperceptions, affirming both the singularity of black oppression and its fundamental connection to enslaving power. In so doing, it enables ethicists to disarm an older racial foe while thwarting the ascension of a newer one.
Assessing the Augustinian Democrats
Authors: Tran Jonathan 
Published: September 2018

AbstractIn this essay I argue that Christian political participation as envisioned by those I term “Augustinian democrats”—a group of Protestant ethicists following a path cleared by Jeffrey Stout’s 2004Democracy and Tradition—is founded upon an elegantly rendered political ontology, but leaves incomplete a description of the practical task and place of the church. My contention is that this incompletely developed practical task is not accidental to the manner in which these Augustinians complete the speculative, ontological task. The completion of the speculative task combined with the incompletion of the practical task, I conclude, nevertheless results in a hybrid and especially interesting picture of personhood that points to an understanding of Protestantism as the attempt to recover human individuality within Christianity.
Religion and Civic Purpose in Sophocles'sPhiloctetes
Authors: Herbel Jerry 
Published: September 2018

AbstractWhy should citizens participate in civic endeavors they oppose? In thePhiloctetes, Sophocles dramatizes the actions of three interlocutors who struggle for answers to an intractable personal and political conflict amid an existential civic crisis. The characters try several methods to resolve the impasse, specifically deceit, sympathy and appeals to duty. Ultimately, civic religion succeeds in creating unity where other methods of resolution fail. The civic religion framework in thePhiloctetescan be seen as Sophocles's statement that resolution of the most extreme political conflicts can be obtained through a combination of piety and reason that respects foundational civic doctrines transcending politics. In this way, civic religion serves to unify political communities divided by self‐interest, intolerance, and desire for revenge while preserving self‐determination and the dignity of free will.
Circulating markers of gut barrier function associated with disease severity in primary sclerosing cholangitis
Authors: Dhillon Amandeep K. , Kummen Martin , Trøseid Marius , Åkra Sissel , Liaskou Evaggelia , Moum Bjørn , Vesterhus Mette , Karlsen Tom H. , Seljeflot Ingebjørg , Hov Johannes R. 
Published: September 2018

AbstractBackground & AimsOne important hypothesis in primary sclerosing cholangitis pathophysiology suggests that bacterial products from an inflamed leaky gut lead to biliary inflammation. We aimed to investigate whether circulating markers of bacterial translocation were associated with survival in a Norwegian primary sclerosing cholangitis cohort.MethodsSerum levels of zonulin, intestinal fatty acid binding protein, soluble CD14, lipopolysaccharide and lipopolysaccharide‐binding protein were measured in 166 primary sclerosing cholangitis patients and 100 healthy controls.ResultsLipopolysaccharide‐binding protein and soluble CD14 were elevated in primary sclerosing cholangitis compared with healthy controls (median 13 662 vs 12 339 ng/mL, P = 0.010 and 1657 vs 1196 ng/mL, P < 0.001, respectively). High soluble CD14 and lipopolysaccharide‐binding protein (values >optimal cut‐off using receiver operating characteristics) were associated with reduced liver transplantation–free survival (P < 0.001 and P = 0.005, respectively). The concentration of soluble CD14 was higher in patients with hepatobiliary cancer compared to other primary sclerosing cholangitis patients and healthy controls. Zonulin was lower in primary sclerosing cholangitis than controls, but when excluding primary sclerosing cholangitis patients with increased prothrombin time zonulin concentrations were similar in primary sclerosing cholangitis and healthy controls. Concomitant inflammatory bowel disease did not influence the results, while inflammatory bowel disease patients without primary sclerosing cholangitis (n = 40) had lower concentration of soluble CD14. In multivariable Cox regression, high soluble CD14 and high lipopolysaccharide‐binding protein were associated with transplantation‐free survival, independent from Mayo risk score (HR: 2.26 [95% CI: 1.15‐4.43], P = 0.018 and HR: 2.00 [95% CI: 1.17‐3.43], P = 0.011, respectively).ConclusionsPrimary sclerosing cholangitis patients show increased levels of circulating markers of bacterial translocation. High levels are associated with poor prognosis measured by transplantation‐free survival, indicating that ongoing gut leakage could have clinical impact in primary sclerosing cholangitis.