bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL‐2 modulates Th2 cell responses to glucocorticosteroid: A cause of persistent type 2 inflammation?
Authors: Kanagalingam Tharsan , Solomon Lauren , Vijeyakumaran Meerah , Palikhe Nami Shrestha , Vliagoftis Harissios , Cameron Lisa 
Published: April 2019

AbstractBackgroundGlucocorticosteroids (GCs) are the main treatment for asthma as they reduce type 2 cytokine expression and induce apoptosis. Asthma severity is associated with type 2 inflammation, circulating Th2 cells and higher GC requirements.ObjectiveThe aim of this study was to assess whether ex vivo production of interleukin 2 (IL‐2), a T‐cell survival factor, associated with clinical features of asthma severity, the proportion of blood Th2 cells and Th2 cell responses to GC.MethodsPeripheral blood from asthma patients (n = 18) was obtained and the proportion of Th2 cells determined by flow cytometry. Peripheral blood cells were activated with mitogen (24 hours) and supernatant levels of IL‐2 and IL‐13 measured by enzyme‐linked immunosorbent assay. In vitro differentiated Th2 cells were treated with dexamethasone (DEX) and IL‐2 and assessed for apoptosis by flow cytometry (annexin V). Level of messenger RNA (mRNA) for antiapoptotic (BCL‐2) and proapoptotic (BIM) genes, IL‐13, GC receptor (GR) and FKBP5 were determined by quantitative real‐time polymerase chain reaction. GR binding was assessed by chromatin immunoprecipitation.ResultsIL‐2 produced by activated peripheral blood cells correlated negatively with lung function and positively with a daily dose of inhaled GC. When patients were stratified based on IL‐2 level, high IL‐2 producers made more IL‐13 and had a higher proportion of circulating Th2 cells. In vitro, increasing the level of IL‐2 in the culture media was associated with resistance to DEX‐induced apoptosis, with more BCL‐2/less BIM mRNA. Th2 cells cultured in high IL‐2 had more IL‐13, less GR mRNA, showed reduced binding of the GR to FKBP5, a known GC‐induced gene, and required higher concentrations of DEX for cytokine suppression.Conclusions and Clinical RelevanceIL‐2 downregulates Th2 cell responses to GC, supporting both their survival and pro‐inflammatory capacity. These results suggest that a patient's potential to produce IL‐2 may be a determinant in asthma severity.
Loss of the Vitamin D Receptor in Human Breast Cancer Cells Promotes Epithelial to Mesenchymal Cell Transition and Skeletal Colonization
Authors: Horas Konstantin , Zheng Yu , Fong-Yee Colette , Macfarlane Eugenie , Manibo Jeline , Chen Yunzhao , Qiao Jeremy , Gao Mingxuan , Haydar Nancy , McDonald Michelle M , Croucher Peter I , Zhou Hong , Seibel Markus J 
Published: April 2019

ABSTRACT
Expression of the vitamin D receptor (VDR) is thought to be associated with neoplastic progression. However, the role of the VDR in breast cancer metastasis to bone and the molecular mechanisms underlying this process are unknown. Employing a rodent model (female Balb/c nu/nu mice) of systemic metastasis, we here demonstrate that knockdown of the VDR strongly increases the metastatic potential of MDA-MB-231 human breast cancer cells to bone, resulting in significantly greater skeletal tumor burden. Ablation of VDR expression promotes cancer cell mobility (migration) and invasiveness, thereby facilitating skeletal colonization. Mechanistically, these changes in tumor cell behavior are attributable to shifts in the expression of proteins involved in cell adhesion, proliferation, and cytoskeletal organization, patterns characteristic for epithelial-to-mesenchymal cell transition (EMT). In keeping with these experimental findings, analyses of human breast cancer specimens corroborated the association between VDR expression, EMT-typical changes in protein expression patterns, and clinical prognosis. Loss of the VDR in human breast cancer cells marks a critical point in oncogenesis by inducing EMT, promoting the dissemination of cancer cells, and facilitating the formation of tumor colonies in bone. © 2019 American Society for Bone and Mineral Research.
Identification of novel mutations in preaxial polydactyly patients through whole‐exome sequencing
Authors: Wang Tao , Xuan Zhaopeng , Dou Yichen , Liu Yang , Fu Yanyan , Ren Jingyan , Lu Laijin 
Published: April 2019

AbstractBackgroundPolydactyly is one of the most common hereditary limb malformation characterized by additional digits in hands and/or feet. With extra fingers/toes, which could be very problematic, polydactyly patients are usually treated in early childhood by removing of extra digits with surgery. Genetically, polydactyly is caused by mutations of genes that involve in digit formation.MethodsIn the current report, we performed genetic analysis for polydactyly using DNA samples from a cohort of 20 Chinese patients. All patients show preaxial polydactyly in one of their hands.ResultsWith whole‐exome sequencing (WES), we have identified two novel heterozygous mutations c.G2844A in GLI3 gene (OMIM 165240) and c.1409_1410del in EVC gene (OMIM 604831). Compound heterozygous mutations that affect KIAA0586 gene (OMIM 610178) are also detected. Proteins encoded by the genes have important roles in primary cilia and regulate sonic hedgehog signaling pathway.ConclusionOur study highlights the important roles of primary cilia in limb development, and helps to further understand the molecular mechanisms for polydactyly formation.
Some properties of transportation network cooperative games
Authors: Gnecco Giorgio , Hadas Yuval , Sanguineti Marcello 
Published: April 2019

AbstractA basic question in network analysis concerns the quantification of the importance of each node in terms of network connectivity. To this end, a possible approach consists in using cooperative game theory tools to define a measure of node centrality. In this paper, given a transportation network, a cooperative game model with transferable utility (TU game) is considered. The nodes of the network represent the players in such a game, and the Shapley values of the nodes are used to measure centrality. The model, called Transportation Network cooperative (TNc) game, integrates within the utility function of the TU game the network topology and the demand. Properties of TNc games and their associated utility functions are investigated. Numerical results are reported, to get insights into the obtained properties.
Intraductal carcinoma of the prostate in the absence of high‐grade invasive carcinoma represents a molecularly distinct type of in situ carcinoma enriched with oncogenic driver mutations
Authors: Khani Francesca , Wobker Sara E , Hicks Jessica L , Robinson Brian D , Barbieri Christopher E , De Marzo Angelo M , Epstein Jonathan I , Pritchard Colin C , Lotan Tamara L 
Published: April 2019

AbstractIntraductal carcinoma of the prostate (IDC‐P) most often appears associated with high‐grade invasive prostate carcinoma (PCa), where it is believed to represent retrograde spread. However, IDC‐P rarely occurs as an isolated finding at radical prostatectomy or with concurrent low‐grade (Grade Group 1) invasive carcinoma. We hypothesized that isolated IDC‐P (iIDC‐P) in these unusual cases may represent a distinct in situ lesion and molecularly profiled 15 cases. iIDC‐P was characterized by copy number alteration (CNA) profiling and targeted next generation sequencing in cases with sufficient tissue (n = 7). Immunohistochemistry for PTEN and ERG was performed on the total cohort (n = 15), where areas of iIDC‐P and associated invasive disease were evaluated separately (n = 9). By copy number profiling, iIDC‐P alterations were similar to those previously described in high‐grade invasive PCa (PTEN, RB1, and CHD1 loss; MYC gain). However, in four cases, targeted sequencing revealed a striking number of activating oncogenic driver mutations in MAPK and PI3K pathway genes, which are extraordinarily rare in conventional PCa. In addition, pathogenic mutations in DNA repair genes were found in two cases of iIDC‐P (BRCA2, CHEK2, CDK12) and other known PCa‐associated mutations (FOXA1, SPOP) in two cases. Overall, ERG was expressed in 7% (1/15) of the iIDC‐P lesions and PTEN was lost in 53% (8/15). Discordance for ERG or PTEN status between IDC‐P and the low‐grade PCa was observed in five of nine cases, with intact PTEN in the invasive tumor and PTEN loss in IDC‐P in four. Despite a CNA profile similar to conventional PCa, iIDC‐P is enriched with potentially targetable oncogenic driver mutations in MAPK/PI3K genes. Based on PTEN and ERG status, iIDC‐P is not likely a precursor to the associated low‐grade invasive PCa, but represents a molecularly unique in situ tumor of unclear clinical significance. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Limitations for health research with restricted data collection from UK primary care
Authors: Strongman Helen , Williams Rachael , Meeraus Wilhelmine , Murray‐Thomas Tarita , Campbell Jennifer , Carty Lucy , Dedman Daniel , Gallagher Arlene M. , Oyinlola Jessie , Kousoulis Antonis , Valentine Janet 
Published: April 2019

AbstractPurposeUK primary care provides a rich data source for research. The impact of proposed data collection restrictions is unknown. This study aimed to assess the impact of restricting the scope of electronic health record (EHR) data collection on the ability to conduct research. The study estimated the consequences of restricted data collection on published Clinical Practice Research Datalink studies from high impact journals or referenced in clinical guidelines.MethodsA structured form was used to systematically analyse the extent to which individual studies would have been possible using a database with data collection restrictions in place: (1) retrospective collection of specified diseases only; (2) retrospective collection restricted to a 6‐ or 12‐year period; (3) prospective and retrospective collection restricted to non‐sensitive data. Outcomes were categorised as unfeasible (not reproducible without major bias); compromised (feasible with design modification); or unaffected.ResultsOverall, 91% studies were compromised with all restrictions in place; 56% studies were unfeasible even with design modification. With restrictions on diseases alone, 74% studies were compromised; 51% were unfeasible. Restricting collection to 6/12 years had a major impact, with 67 and 22% of studies compromised, respectively. Restricting collection of sensitive data had a lesser but marked impact with 10% studies compromised.ConclusionEHR data collection restrictions can profoundly reduce the capacity for public health research that underpins evidence‐based medicine and clinical guidance. National initiatives seeking to collect EHRs should consider the implications of restricting data collection on the ability to address vital public health questions.
An Anisotropic Elastoviscoplasticity Model of Thermomechanical Responses of Shocked β‐HMX and α‐RDX Single Crystals
Authors: Wang XinJie , Wu YanQing , Huang FengLei , Hu WeiJia , Liu YuCun 
Published: April 2019

AbstractAn anisotropic elastoviscoplasticity constitutive model for β‐cyclotetramethylene tetranitramine (β‐HMX) and α‐cyclotrimethylene trinitramine single crystals (α‐RDX) is developed to analyze the thermomechanical responses under shock loading. The model considers nonlinear, pressure and temperature dependent elasticity, and dislocation‐based plasticity which incorporate regenerative multiplication and heterogeneous nucleation mechanisms. The proposed model is calibrated against experimental wave profiles of (011), (010), (100),
,
and
orientations of HMX single crystals and (210), (100),
,
and (111) orientations of RDX single crystals. The model can well capture elastoplastic double wave structure, stress relaxation after the Hugoniot elastic limit as well as the arrival of plastic wave. Moreover, pressure, accumulated shear strain, and temperature contours of both HMX and RDX show obvious anisotropy and non‐uniform spatial distribution, which is explained by analyzing dislocation activity with corresponding resolved shear stress on slip systems. Results provide insights into understanding ignition mechanisms and predicting ignition sensitivity of explosive single crystals as well as polymer bonded explosives at the mesoscale.
Translation‐coupled protein folding assay using a protease to monitor the folding status
Authors: Niwa Tatsuya , Uemura Eri , Matsuno Yuki , Taguchi Hideki 
Published: April 2019

AbstractProtein folding is an essential prerequisite for proteins to execute nearly all cellular functions. There is a growing demand for a simple and robust method to investigate protein folding on a large‐scale under the same conditions. We previously developed a global folding assay system, in which proteins translated using an Escherichia coli‐based cell‐free translation system are centrifuged to quantitate the supernatant fractions. Although the assay is based on the assumption that the supernatants contain the folded native states, the supernatants also include nonnative unstructured proteins. In general, proteases recognize and degrade unstructured proteins, and thus we used a protease to digest the unstructured regions to monitor the folding status. The addition of Lon protease during the translation of proteins unmasked subfractions, not only in the soluble fractions but also in the aggregation‐prone fractions. We translated ∼90 E. coli proteins in the protease‐inclusion assay, in the absence and presence of chaperones. The folding assay, which sheds light on the molecular mechanisms underlying the aggregate formation and the chaperone effects, can be applied to a large‐scale analysis.
M‐Branes: Lessons from M2's and Hopes for M5's
Authors: Lambert Neil 
Published: April 2019

AbstractIn this talk we will review the construction of M2‐brane SCFT's highlighting some novelties and the role of 3‐algebras. Parts of our discussion will closely follow parts of [1]. Next we will discuss M5‐branes: the basics, the obstacles as well as various attempts to construct the associated SCFT and potential relations between M2‐branes and M5‐branes.
Role of iron in cancer development by viruses
Authors: Shoja Zabihollah , Chenari Maryam , Jafarpour Ali , Jalilvand Somayeh 
Published: April 2019

SummaryIncreased levels of iron in body are attributed to higher cancer risk. Given the fact that 16% of all human cancers are caused by viral infections, iron is suggested to play an important role in carcinogenesis particularly those induced by viral infections. The present study provides an updated summary of the literature and the plausible mechanisms of iron involvement in cancer development by viruses. Our understanding about the interplay between viral infections and iron in different settings particularly cancer development is yet to be improved as it may shed a new light in development of new therapeutic strategies.
Ultrafine Ru/RuOx Nanoparticles Uniformly Anchored on Carbon Nanotubes as Cathode Electrocatalyst for Lithium‐Oxygen Batteries
Authors: Zhang Yaowen , Wang Xiaogang , Yin Jianjun , Wang Yifeng , Li Chao , Xia Dingguo 
Published: April 2019

AbstractThe nonaqueous lithium‐oxygen (Li‐O2) battery possesses extremely high theoretical energy density which is considered as one of the most fascinating next‐generation energy storage systems. However, the sluggish oxygen redox reaction kinetics in the cathode of Li‐O2 battery severely limits its practical application. The incorporation of cathode electrocatalyst with high activity is an effective strategy to address this issue. Herein we report a novel electrocatalyst of ultrafine Ru/RuOx nanoparticles (NPs) decorated on the surface of carbon nanotubes (Ru/RuOx@CNTs) synthesized by a facile modified ethylene glycol reduction method. The as‐prepared Ru/RuOx@CNTs electrocatalyst as cathode for Li‐O2 battery delivers high initial discharge specific capacity up to 3795 mAh g−1, low overpotential and preferable cycle stability of 113 cycles with a limited specific capacity of 500 mAh g−1 at 0.1 mA cm−2 compared with CNTs cathode, which is originated from the well‐dispersed Ru/RuOx nanoparticles on CNTs, leading to efficient electrocatalytic activities for oxygen reduction and evolution reactions.
α‐Fe2O3 Nanoparticles Decorated C@MoS2 Nanosheet Arrays with Expanded Spacing of (002) Plane for Ultrafast and High Li/Na‐Ion Storage
Authors: Zhan Jing , Wu Kuan , Yu Xue , Yang Mengjia , Cao Xu , Lei Bo , Pan Dengyu , Jiang Hu , Wu Minghong 
Published: April 2019

AbstractMoS2 nanosheets as a promising 2D nanomaterial have extensive applications in energy storage and conversion, but their electrochemical performance is still unsatisfactory as an anode for efficient Li+/Na+ storage. In this work, the design and synthesis of vertically grown MoS2 nanosheet arrays, decorated with graphite carbon and Fe2O3 nanoparticles, on flexible carbon fiber cloth (denoted as Fe2O3@C@MoS2/CFC) is reported. When evaluated as an anode for lithium‐ion batteries, the Fe2O3@C@MoS2/CFC electrode manifests an outstanding electrochemical performance with a high discharge capacity of 1541.2 mAh g−1 at 0.1 A g−1 and a good capacity retention of 80.1% at 1.0 A g−1 after 500 cycles. As for sodium‐ion batteries, it retains a high reversible capacity of 889.4 mAh g−1 at 0.5 A g−1 over 200 cycles. The superior electrochemical performance mainly results from the unique 3D ordered Fe2O3@C@MoS2 array‐type nanostructures and the synergistic effect between the C@MoS2 nanosheet arrays and Fe2O3 nanoparticles. The Fe2O3 nanoparticles act as spacers to steady the structure, and the graphite carbon could be incorporated into MoS2 nanosheets to improve the conductivity of the whole electrode and strengthen the integration of MoS2 nanosheets and CFC by the adhesive role, together ensuring high conductivity and mechanical stability.
Stochastic density functional theory
Authors: Fabian Marcel D. , Shpiro Ben , Rabani Eran , Neuhauser Daniel , Baer Roi 
Published: April 2019

Linear‐scaling implementations of density functional theory (DFT) reach their intended efficiency regime only when applied to systems having a physical size larger than the range of their Kohn–Sham density matrix (DM). This causes a problem since many types of large systems of interest have a rather broad DM range and are therefore not amenable to analysis using DFT methods. For this reason, the recently proposed stochastic DFT (sDFT), avoiding exhaustive DM evaluations, is emerging as an attractive alternative linear‐scaling approach. This review develops a general formulation of sDFT in terms of a (non)orthogonal basis representation and offers an analysis of the statistical errors (SEs) involved in the calculation. Using a new Gaussian‐type basis‐set implementation of sDFT, applied to water clusters and silicon nanocrystals, it demonstrates and explains how the standard deviation and the bias depend on the sampling rate and the system size in various types of calculations. We also develop a basis‐set embedded‐fragments theory, demonstrating its utility for reducing the SEs for energy, density of states and nuclear force calculations. Finally, we discuss the algorithmic complexity of sDFT, showing it has CPU wall‐time linear‐scaling. The method parallelizes well over distributed processors with good scalability and therefore may find use in the upcoming exascale computing architectures.This article is categorized under:

Electronic Structure Theory > Ab Initio Electronic Structure Methods
Structure and Mechanism > Computational Materials Science
Electronic Structure Theory > Density Functional Theory
Removing ammonium from underground water by strengthening Mn(III) generation through electrochemical reduction
Authors: Shi Xinxin , Shi Julian , Ma Wenhan , Chai Peixu , Huang Tinglin 
Published: April 2019

AbstractManganese oxide has been found to be an active catalyst for ammonium oxidation. This work presented an innovative electrochemical system to improve the removal efficiency of ammonium by strengthening the generation of Mn(III). In this system, the manganese oxide coating activated carbon (MnOx/AC) particles were used as the cathode of a fuel cell (MnOx/AC‐Ca). Compared to the conventional method using MnOx in a nonelectrochemical system (MnOx/AC‐Control), the ammonium removal efficiency was doubled in the MnOx/AC‐Ca system. Conversely, when using MnOx as the anode of a fuel cell (MnOx/AC‐An), the ammonium removal efficiency was lower than that in the MnOx/AC‐Control system. XPS results showed that Mn(III) in the MnOx/AC‐Ca system was obviously higher than that in the MnOx/AC‐Control system. Conversely, more Mn(IV), which was less active than Mn(III) for removal, was detected in the MnOx/AC‐An system. The possible pathway for the ammonium removal by MnOx was that Mn(III) reacted with and produced Mn2+. These Mn2+ were then reoxidized into new active MnOx under the self‐catalysis of MnOx, resulting in a continuous ammonium removal. Moreover, nitrite, the intermediate product of ammonium oxidation, can be oxidized by MnOx, thus helping the ammonium oxidation process.Practitioner points

Mn(III) was generated by using MnOx as the cathode of fuel cells.

Ammonium removal efficiency went up with the content of Mn(III) in MnOx.

Mechanism of the removal by MnOx was discussed.
Recombination in yeast based on six base pairs of homologous sequences: Structural instability in two sets of isomeric model expression plasmids
Authors: Hohnholz Ruben , Achstetter Tilman 
Published: April 2019

AbstractMulticopy episomal yeast (Saccharomyces cerevisiae) plasmids are frequently employed in research and industrial production despite their known limited structural and segregational stability. Employing a set of six yEGFP3 model expression plasmids (identical in size but differing in the arrangement of their functional sequences, joined via six base pair SacI sequences), we used back transformation of total DNA extracted from yeast transformants into Escherichia coli to detect potential plasmid rearrangements. This approach revealed deletions, translocations, duplications, and flippings of functional sequences in our plasmids based on homologous recombination between the SacI sequences. To extend our findings, we assembled and analysed in the same way a corresponding plasmid set of six isoforms expressing the antibacterial insect peptide defensin A. In 833 individual ampR clones (both sets combined), we traced 28 cases (3.4%) with precise structural changes. However, the frequency in one isoform in the pIFC4.13X series, pIFC4.131, was particularly high with 18.5% (15 out of 81 clones), indicating that the architecture of this plasmid is unfavourable to the host. With an increased sensitivity, a Polymerase Chain Reaction (PCR) approach revealed further structural changes in at least half of the isoforms of each set. The changes are considered the consequence of homologous recombination events involving the SacI sequences in a random fashion. The frequency of plasmid alterations is the product of selection and counterselection seemingly favouring or disfavouring certain structures. Although no sole architectural arrangement stuck out as being particularly stable, we were able to determine with our approach unfavourable sequence associations that should be avoided.