bluuebunny/crossref_metadata_2025_split huggingface dataset:
lptG contributes to changes in membrane permeability and the emergence of multidrug hypersusceptibility in a cystic fibrosis isolate of Pseudomonas aeruginosa
Authors: Harrison Lucas B. , Fowler Randal C. , Abdalhamid Baha , Selmecki Anna , Hanson Nancy D. 
Published: April 2019

AbstractPurposeIn the lungs of cystic fibrosis patients, Pseudomonas aeruginosa is exposed to a myriad of antibiotics leading to alterations in antibiotic susceptibility. This study identifies mutations resulting in hypersusceptibility in isogenic mutants of a P. aeruginosa clinical isolate, PA34.MethodsPA34 was exposed to subinhibitory concentrations of doripenem or meropenem during growth to mid‐log phase. Antibiotic susceptibility of surviving colonies was determined by agar dilution. Two carbapenem‐resistant colonies hypersusceptible to non‐carbapenem antibiotics were selected for further analysis. Antibiotic resistance gene expression was evaluated by RT‐rtPCR and OprD production by SDS‐PAGE. PA34 and isogenic mutants were evaluated with whole genome sequencing. Sequence variants were confirmed by Sanger sequencing, and cognate genes in eight carbapenem‐resistant clinical isolates hypersusceptible to non‐carbapenem antibiotics were sequenced. Lipopolysaccharide preparations of PA34 and hypersusceptible mutants were evaluated with ProQ‐Emerald stain.ResultsIsogenic mutants showed 4‐ to 8‐fold MIC increase for imipenem, meropenem, and doripenem. However, they were hypersusceptible (≥4‐fold MIC decrease) to aminoglycosides, fluoroquinolones, and non‐carbapenem β‐lactams. Expression of ampC or mex‐opr efflux pumps was unchanged, but OprD production was decreased. Mutations causing Q86H AlgU and G77C LptG amino acid substitutions and nonsense mutations within OprD were observed in both mutants. Lipopolysaccharide modifications were observed between isogenic mutants and PA34. Non‐synonymous mutations in LptF or LptG were observed in 6/8 hypersusceptible clinical isolates resistant to carbapenem antibiotics.ConclusionEvaluation of hypersusceptible mutants identified the association between lptG and a hypersusceptible phenotype. Modifications in lipopolysaccharide profiles suggests LptG modification interferes with lipopolysaccharide transport and contributes to hypersusceptibility.
Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives
Authors: Sun Xin , Yan Peiyi , Zou Chang , Wong Yin‐Kwan , Shu Yuhan , Lee Yew Mun , Zhang Chongjing , Yang Nai‐Di , Wang Jigang , Zhang Jianbin 
Published: April 2019

AbstractArtemisinin and its derivatives, with their outstanding clinical efficacy and safety, represent the most effective and impactful antimalarial drugs. Apart from its antimalarial effect, artemisinin has also been shown to exhibit selective anticancer properties against multiple cancer types both in vitro and in vivo. Specifically, our previous studies highlighted the therapeutic effects of artemisinin on autophagy regulation. Autophagy is a well‐conserved degradative process that recycles cytoplasmic contents and organelles in lysosomes to maintain cellular homeostasis. The deregulation of autophagy is often observed in cancer cells, where it contributes to tumor adaptation to nutrient‐deficient tumor microenvironments. This review discusses recent advances in the anticancer properties of artemisinin and its derivatives via their regulation of autophagy, mitophagy, and ferritinophagy. In particular, we will discuss the mechanisms of artemisinin activation in cancer and novel findings regarding the role of artemisinin in regulating autophagy, which involves changes in multiple signaling pathways. More importantly, with increasing failure rates and the high cost of the development of novel anticancer drugs, the strategy of repurposing traditional therapeutic Chinese medicinal agents such as artemisinin to treat cancer provides a more attractive alternative. We believe that the topics covered here will be important in demonstrating the potential of artemisinin and its derivatives as safe and potent anticancer agents.
Prediction of Protein Metal Binding Sites Using Deep Neural Networks
Authors: Haberal İsmail , Oğul Hasan 
Published: April 2019

AbstractMetals have crucial roles for many physiological, pathological and diagnostic processes. Metal binding proteins or metalloproteins are important for metabolism functions. The proteins that reach the three‐dimensional structure by folding show which vital function is fulfilled. The prediction of metal‐binding in proteins will be considered as a step‐in function assignment for new proteins, which helps to obtain functional proteins in genomic studies, is critical to protein function annotation and drug discovery. Computational predictions made by using machine learning methods from the data obtained from amino acid sequences are widely used in the protein metal‐binding and various bioinformatics fields. In this work, we present three different deep learning architectures for prediction of metal‐binding of Histidines (HIS) and Cysteines (CYS) amino acids. These architectures are as follows: 2D Convolutional Neural Network, Long‐Short Term Memory and Recurrent Neural Network. Their comparison is carried out on the three different sets of attributes derived from a public dataset of protein sequences. These three sets of features extracted from the protein sequence were obtained using the PAM scoring matrix, protein composition server, and binary representation methods. The results show that a better performance for prediction of protein metal‐ binding sites is obtained through Convolutional Neural Network architecture.
Application of failure mode and effects analysis to optimization of linac quality controls protocol
Authors: Bonfantini Francesca , Giandini Tommaso , Meroni Silvia , Cavallo Anna , Stucchi Claudio , Carrara Mauro , Mongioj Valeria , Veronese Ivan , Pignoli Emanuele 
Published: April 2019

PurposeTo apply Failure Mode and Effects Analysis (FMEA) to optimize linac quality control (QC) protocol in order to ensure patient safety and treatment quality, taking maximum advantage of the available resources.Material and methodsEach parameter tested by the QC was considered as a potential failure mode (FM). For each FM, likelihood of occurrence (O), severity of effect (S), and lack of detectability (D) were evaluated and corresponding Risk Priority Number (RPN) was calculated from the product of three indexes. The scores were assigned using two methods: (a) A survey submitted to the medical physicists; (b) A semi‐quantitative analysis (SQA) performed through: simulation of FMs in the treatment planning system; studies reported in literature; results obtained by the QC data analysis. A weighted RPN for all FMs was calculated taking into account both the methods. For each linac, the tests were then sorted by their frequency and the RPN value.ResultsA high variability was found in the scores of the survey, although in many it was reduced in RPN values, highlighting the more relevant tests as on beam output and imaging system. Integrating these results with those obtained by SQA, the RPN‐based ranking of tests has been provided considering the specific use of the accelerator: for example, more accurate tests on dose modulation and multileaf collimator speed were required in linacs where intensity‐modulated treatment is performed, while, more specific tests on couch and jaw position indicators were necessary where treatments with multiple isocenters and/or junctions between adjacent fields were often delivered.ConclusionsFailure Mode and Effects Analysis is a useful tool to prioritize the linac QCs, taking into account the specific equipment and clinical practice. The integration of SQA and survey results reduces subjectivity of the FMEA scoring and allows to optimize linac QCs without “losing” the expertise and experience of medical physicists and clinical staff.
Beyond VNFM: Filling the gaps of the ETSI VNF manager to fully support VNF life cycle operations
Authors: Venâncio Giovanni , Garcia Vinícius Fulber , da Cruz Marcuzzo Leonardo , Tavares Thales Nicolai , Franco Muriel Figueredo , Bondan Lucas , Schaeffer‐Filho Alberto Egon , Paula dos Santos Carlos Raniery , Granville Lisandro Zambenedetti , P. Duarte Elias 
Published: April 2019

SummaryOne of the main challenges to use network functions virtualization (NFV) is to properly manage the life cycle of the virtualized network functions (VNFs). Current solutions based on the ETSI standard NFV architectural framework are complex and require the knowledge of a myriad of details of the underlying infrastructure. This work proposes a VNF manager (VNFM) specification that supports different platforms and VNF utilization scenarios. The proposed VNFM specification defines a set of APIs, modules, and components, for both the end user and the back‐end that provide the fundamental set of operations required to fully manage the VNF life cycle. Our primary goal is to simplify the operations, in particular reducing the need for the network operator to know the details of the virtualized infrastructure. Note that the proposed solution fills a gap and complements the ETSI VNFM module. A prototype was implemented, and experimental results show the effectiveness and low overhead of the proposed solution.
Distributed model predictive control for energy management in a network of microgrids using the dual decomposition method
Authors: Razzanelli Matteo , Crisostomi Emanuele , Pallottino Lucia , Pannocchia Gabriele 
Published: April 2019

SummaryThis paper deals with the application of model predictive control (MPC) to optimize power flows in a network of interconnected microgrids (MGs). More specifically, a distributed MPC (DMPC) approach is used to compute for each MG how much active power should be exchanged with other MGs and with the outer power grid. Due to the presence of coupled variables, the DMPC approach must be used in a suitable way to guarantee the feasibility of the consensus procedure among the MGs. For this purpose, we adopt a tailored dual decomposition method that allows us to reach a feasible solution while guaranteeing the privacy of single MGs (ie, without having to share private information like the amount of generated energy or locally consumed energy). Simulation results demonstrate the features of the proposed cooperative control strategy and the obtained benefits with respect to other classical centralized control methods.
Optimal control measures for a susceptible‐carrier‐infectious‐recovered‐susceptible malware propagation model
Authors: Gonçalves João N.C. , Rodrigues Helena Sofia , Monteiro M. Teresa T. 
Published: April 2019

SummaryPurposing to lessen malware propagation, this paper proposes optimal control measures for a susceptible‐carrier‐infectious‐recovered‐susceptible (SCIRS) epidemiological model formed by a system of ordinary differential equations. By taking advantage of real‐world data related to the number of reported cybercrimes in Japan from 2012 to 2017, an optimal control problem is formulated to minimize the number of infected devices in a cost‐effective way. The existence and uniqueness of the results related to the optimality system are proved. Overall, numerical simulations show the usefulness of the proposed control strategies in reducing the spread of malware infections.
Structure‐Activity Relationship of NF023 Derivatives Binding to XIAP‐BIR1
Authors: Sorrentino Luca , Cossu Federica , Milani Mario , Malkoc Bilge , Huang Wen‐Chieh , Tsay Shwu‐Chen , Ru Hwu Jih , Mastrangelo Eloise 
Published: April 2019

AbstractInhibitors of Apoptosis Proteins (IAPs) are conserved E3‐ligases that ubiquitylate substrates to prevent apoptosis and activate the NF‐kB survival pathway, often deregulated in cancer. IAPs‐mediated regulation of NF‐kB signaling is based on the formation of protein complexes by their type‐I BIR domains. The XIAP‐BIR1 domain dimerizes to bind two TAB1 monomers, leading to downstream NF‐kB activation. Thus, impairment of XIAP‐BIR1 dimerization could represent a novel strategy to hamper cell survival in cancer. To this aim, we previously reported NF023 as a potential inhibitor of XIAP‐BIR1 dimerization. Here we present a thorough analysis of NF023 binding to XIAP‐BIR1 through biochemical, biophysical and structural data. The results obtained indicate that XIAP‐BIR1 dimerization interface is involved in NF023 binding, and that NF023 overall symmetry and the chemical features of its central moiety are essential for an efficient interaction with the protein. Such strategy provides original hints for the development of novel BIR1‐specific compounds as pro‐apoptotic agents.
Who Benefits from Accountability‐Driven School Closure? Evidence from New York City
Authors: Bifulco Robert , Schwegman David J. 
Published: April 2019

AbstractWe estimate the effects of accountability‐driven school closure in New York City on students who attended middle schools that were closed at the time of closure and students who would have likely attended a closed middle school had it remained open. We find that students who would have entered the closed school had it not closed attended schools that perform better on standardized exams and have higher value‐added measures than did the closed schools. While we find that closure did not have any measurable effect on the average student in this group, we do find that high‐performing students in this group attended higher‐performing schools and experienced economically‐meaningful and statistically‐significant improvements in their 6th‐, 7th‐, and 8th‐grade math test scores. We find that these benefits persisted for several cohorts after closure. We also find that closure adversely affected students, low‐performing students in particular, who were attending schools that closed. For policymakers, our results highlight a key trade‐off of closing a low‐performing school: future cohorts of relatively high‐performing students may benefit from closure while low‐performing students in schools designated for closure are adversely affected.
Preparation and mechanism of polyurethane prepolymer and boric acid co‐modified phenolic foam composite: Mechanical properties, thermal stability, and flame retardant properties
Authors: Xu Wenzong , Chen Rui , Xu Jiaying , Wang Guisong , Cheng Chuanming , Yan Hongyi 
Published: April 2019

In this work, a new kind of co‐modified phenolic foam was synthesized with polyurethane prepolymer (PUP) and H3BO3 by a simple preparation method. Firstly, in order to determine the optimal amount of PUP, the effects of different PUP additions on the mechanical properties, foam microstructure, and pulverization rate of phenolic foam were investigated. Then H3BO3 was added to toughened phenolic foam, in order to reduce its fire hazard. The results showed that the mechanical properties of the PFPUP8 phenolic foam composite were the best when the PUP content was 8 wt%. It had a small and regular cell structure, and its pulverization ratio was reduced by 80% compared with that of pristine phenolic foam. Meanwhile, the flame retardant properties of PFPUP8 were improved in different degrees with an increase in the amount of H3BO3. Particularly, when the addition of H3BO3 was 10 wt%, the peak heat release rate, the total heat release, and the total smoke release values of PFPUP10B were decreased by 35.4%, 42.4%, and 45.2%, respectively, compared with those of PFPUP8. The value of the limit oxygen index was increased by 33.1%. Besides, the addition of H3BO3 had no adverse effect on the mechanical properties and pulverization ratio of PFPUP8. In addition, the specific mechanisms of toughening, flame retardant, and smoke suppression are also discussed in this paper on the basis of an investigation into the thermal properties of the toughened flame retardant foam composites by thermogravimetric analysis in N2 atmosphere.
Development and characterization of fully bio‐based polybenzoxazine‐silica hybrid composites for low‐k and flame‐retardant applications
Authors: Krishnamoorthy Krishnadevi , Subramani Devaraju , Eeda Naveena , Muthukaruppan Alagar 
Published: April 2019

In the present work, new classes of bio‐based polybenzoxazines were synthesized using eugenol as phenol source and furfurylamine and stearylamine as amine sources separately through solventless green synthetic process routes and were further reinforced with varying percentages (1, 3, 5, and 10 wt%) of silica (from rice husk) to attain hybrid composites. The molecular structure, cure behaviour, thermal stability, dielectric properties, and flame‐retardant behaviour of both benzoxazine monomers and benzoxazine composites were characterized using appropriate modern analytical techniques. The eugenol‐based benzoxazines synthesized using furfurylamine (FBz) and stearylamine (SBz) were cured at 223°C and 233°C, respectively. The differential scanning calorimetry (DSC) data reveal the glass transition temperatures (Tg) of FBz and SBz were 157°C and 132°C, respectively, and the maximum decomposition temperature (Tmax) as obtained from thermogravimetric analysis (TGA), were found to be 464°C and 398°C for FBz and SBz, respectively. The dielectric constants for FBz and SBz obtained at 1 MHz were 3.28 and 3.62, respectively. Furthermore, varying weight percentages (1, 3, 5, and 10 wt%) of 3‐mercaptopropyltrimethoxysilane (3‐MPTMS) functionalized bio‐silica reinforced the composite materials as evidenced by their improved thermal stability and lower dielectric constant. Data obtained from thermal and dielectric studies suggested that these polybenzoxazines could be used in the form of adhesives, sealants, and composites for high performance inter‐layer low‐k dielectric applications in microelectronics.
Characterization of pediatric hepatocellular carcinoma reveals genomic heterogeneity and diverse signaling pathway activation
Authors: Haines Katherine , Sarabia Stephen F. , Alvarez Karla R. , Tomlinson Gail , Vasudevan Sanjeev A. , Heczey Andras A. , Roy Angshumoy , Finegold Milton J. , Parsons D. Williams , Plon Sharon E. , López‐Terrada Dolores 
Published: April 2019

AbstractBackgroundPediatric hepatocellular carcinoma (HCC) is a rare liver tumor in children with a poor prognosis. Comprehensive molecular profiling to understand the underlying genomic drivers of this tumor has not been completed, and it is unclear whether nonfibrolamellar pediatric HCC is more genomically similar to hepatoblastoma or adult HCC.ProcedureTo characterize the molecular landscape of these tumors, we analyzed a cohort of 15 pediatric non‐FL‐HCCs by sequencing a panel of cancer‐associated genes and conducting copy‐number and gene‐expression analyses.ResultsWe detected multiple types of molecular alterations in Wnt signaling genes, including APC inversion, AMER1 somatic mutation, and most commonly CTNNB1 intragenic deletions. There were multiple alterations to the telomerase pathway via TERT activation or ATRX mutation. Therapeutically targetable activating mutations in MAPK/ERK signaling pathway genes, including MAPK1 and BRAF, were detected in 20% of tumors. TP53 mutations occurred far less frequently in our pediatric HCC cohort than reported in adult cohorts. Tumors arising in children with underlying liver disease were found to be molecularly distinct from the remainder and lacking detectable oncogenic drivers, as compared with those arising in patients without a history of underlying liver disease; the majority of both types were positive for glypican‐3, another potential therapeutic target.ConclusionOur study revealed pediatric HCC to be a molecularly heterogeneous group of tumors. Those non‐FL‐HCC tumors arising in the absence of underlying liver disease harbor genetic alterations affecting multiple cancer pathways, most notably Wnt signaling, and share some characteristics with adult HCC.
Identification, Quantification, and System Analysis of Protein N‐ε Lysine Methylation in Anucleate Blood Platelets
Authors: Rocheleau Anne D. , Melrose Alexander R. , Cunliffe Jennifer M. , Klimek John , Babur Özgün , Tassi Yunga Samuel , Ngo Anh T. P. , Pang Jiaqing , David Larry L. , McCarty Owen J. T. , Aslan Joseph E. 
Published: April 2019

AbstractProtein posttranslational modifications critically regulate a range of physiological and disease processes. In addition to tyrosine, serine, and threonine phosphorylation, reversible N‐ε acylation and alkylation of protein lysine residues also modulate diverse aspects of cellular function. Studies of lysine acyl and alkyl modifications have focused on nuclear proteins in epigenetic regulation; however, lysine modifications are also prevalent on cytosolic proteins to serve increasingly apparent, although less understood roles in cell regulation. Here, the methyl‐lysine (meK) proteome of anucleate blood platelets is characterized. With high‐resolution, multiplex MS methods, 190 mono‐, di‐, and tri‐meK modifications are identified on 150 different platelet proteins—including 28 meK modifications quantified by tandem mass tag (TMT) labeling. In addition to identifying meK modifications on calmodulin (CaM), GRP78 (HSPA5, BiP), and EF1A1 that have been previously characterized in other cell types, more novel modifications are also uncovered on cofilin, drebin‐like protein (DBNL, Hip‐55), DOCK8, TRIM25, and numerous other cytoplasmic proteins. Together, the results and analyses support roles for lysine methylation in mediating cytoskeletal, translational, secretory, and other cellular processes. MS data for this study have been deposited into the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD012217.
Star‐shaped siloxane polymers with various cyclic cores: Synthesis and properties
Authors: Vysochinskaya Yulia S. , Anisimov Anton A. , Peregudov Alexander S. , Dubovik Alexander S. , Orlov Vladimir N. , Malakhova Yulia N. , Stupnikov Alexey A. , Buzin Mikhail I. , Nikiforova Galina G. , Vasil'ev Victor G. , Shchegolikhina Olga I. , Muzafarov Aziz M. 
Published: April 2019

ABSTRACTSix new star‐shaped polydimethylsiloxane (PDMS) with various cyclic siloxane cores were synthesized by the “grafting onto” method. The polymers obtained feature low dispersity and well‐defined structures. Two of them, Q
8‐PDMS and D
12‐PDMS, have a three‐dimensional spatial structure traditional for star‐shaped polymers where the arms are arranged in all directions from the branching center. The other four polymers, D
4‐PDMS–D
8‐PDMS, have quite a different spatial geometry (cis‐structure) where all the PDMS‐arms are arranged on one side of the branching center plane. Such star‐shaped structures were not reported before. The structures and purity of the polymers obtained were confirmed using a set of physicochemical methods of analysis. The effect of the macromolecule structure on the properties of the target polymers was identified. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019
Characterization of the deposition behavior and changes in bonding structures of hexamethyldisiloxane and decamethylcyclopentasiloxane atmospheric plasma‐deposited films*
Authors: Gilliam Mary A. , Farhat Susan A. , Garner Graham E. , Stubbs Barrack P. , Peterson Benjamin B. 
Published: April 2019

AbstractThe plasma deposition behavior of hexamethyldisiloxane (HMDSO) and decamethylcyclopentasiloxane (D5) is investigated for an atmospheric pressure plasma jet. The energy‐deficient and monomer‐deficient domains are revealed by normalized parameters and no significant difference between HMDSO and D5 is observed. The results are supported by Fourier‐transform infrared spectroscopy (FTIR) and X‐ray photoelectron spectroscopy. The data is also evaluated using an Arrhenius‐type equation and an empirical equation reported in the literature, but the correlation is not as good as the normalized parameters. Changes in Si–O–Si bonding arrangements are analyzed by deconvolution of the FTIR absorbance band, showing an increase in porous cage structures with higher normalized energy input.