bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promyelocytic leukaemia protein links DNA damage response and repair to hepatitis B virus‐related hepatocarcinogenesis
Authors: Chung Yih‐Lin , Wu Mei‐Ling 
Published: April 2013

AbstractDNA damage response and repair pathways are important barriers to carcinogenesis. Here, we show that promyelocytic leukaemia (PML, also known as TRIM19), involved in sensing DNA damage and executing homologous recombination repair, is down‐regulated in non‐tumour liver cells surrounding hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC). No PML mutation or deletion was found in HBV‐infected liver or HCC cells. Immunohistochemical analysis of liver biopsies from patients with breast or liver cancer and HBV reactivation after chemotherapy revealed PML up‐regulation and HBV exacerbation in normal liver tissue in response to DNA damage (functional PML), PML down‐regulation in HCC peritumour cells associated with high HBsAg accumulation and low HBV replication activity (suppressive PML), and heterogeneous nuclear PML expression in HCC cells that lost HBV DNA and HBsAg and were non‐reactive to DNA damage (dysregulated PML). Loss of PML in HBsAg‐transgenic mice promoted chromosome breaks in liver cells and accelerated the accumulation of body and liver fat and the development of a liver steatosis–dysplasia–adenoma–carcinoma sequence in an inflammation‐independent and male‐predominant manner, compared to PML knock‐out or HBsAg‐transgenic mice during the same time period. These results indicate that PML deficiency facilitates genomic instability and promotes HBsAg‐related hepatocarcinogenesis, which also involves androgen and lipid metabolism. These findings uncover a novel PML link between HBV‐related tumourigenesis, DNA repair, and metabolism. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Characterisation of Homoflavonoids from Three Ophioglossum Species Using Liquid Chromatography with Diode Array Detection and Electrospray Ionisation Tandem Mass Spectrometry
Authors: Wan Chuan‐Xing , Luo Jian‐Guang , Gu Yu‐Cheng , Xu De‐Ran , Kong Ling‐Yi 
Published: April 2013

ABSTRACTIntroductionHomoflavonoids, characterised by one more carbon atom directly added to C6–C3–C6 backbone of flavonoids, are rich in the species of genus Ophioglossum. Up to now we have little knowledge about their MS fragmentation patterns. It is therefore necessary to investigate their MS fragmentation pathways so as to distinguish them from other types of flavonoids.ObjectiveTo develop a rapid method for identifying homoflavonoids from Ophioglossum based on their characteristic MS fragmentation.MethodsMass spectrometry fragmentation pathways and qualitative analysis of homoflavonoids in three ferns of Ophioglosssum were investigated by using high‐performance liquid chromatography coupled with diode‐array detection and electrospray ionisation tandem mass spectrometry (HPLC–DAD–ESI/MSn).ResultsThe analyses of the MSn spectra of the homoflavonoids allowed us to classify them into two types according to their fragmentation characteristics. The type I homoflavonoids, with an attached additional carbon atom to the C‐3 position of the C‐ring, presented the initial competing loss of H2O and CH2O from their aglycone ions, compared to the initial removal of H2O or CO in the case of the type II homoflavonoids, which bear the additional carbon atom at the C‐2’ site of the B‐ring and forming ring D. The above characteristic fragmentations of homoflavonoids were quite different from those of other flavonoids, and were successfully applied to identify homoflavonoids in the crude extracts of three Ophioglossum species.ConclusionThe HPLC–DAD–ESI/MSn method obtained in the present study provided a powerful tool for identifying homoflavonoids from ferns in the genus Ophioglossum. Copyright © 2013 John Wiley & Sons, Ltd.
Intrinsically conducting polymer‐based fabric strain sensors
Authors: Ma Sude , Wang Yan , Min Zhonghua , Zhong Lisheng 
Published: April 2013

AbstractFabric strain sensors based on intrinsically conducting polymers (ICPs) have been extensively studied recently owing to their ease of preparation, unique properties and many potential applications. Research on ICP‐based fabric strain sensors, including fabrication, performance and applications of the sensors, is summarized and reviewed in this paper. The conductivity and morphology of ICP‐coated fabrics can be easily adjusted by controlling the synthesis conditions, leading to sensors with varied performances. Moreover, the performances of the sensors can be controlled by various other choices, such as selecting the right fabric substrates, the appropriate stretching directions, etc., giving these sensors many potential applications. © 2013 Society of Chemical Industry
What is the best reference state for designing statistical atomic potentials in protein structure prediction?
Authors: Deng Haiyou , Jia Ya , Wei Yanyu , Zhang Yang 
Published: April 2013

AbstractMany statistical potentials were developed in last two decades for protein folding and protein structure recognition. The major difference of these potentials is on the selection of reference states to offset sampling bias. However, since these potentials used different databases and parameter cutoffs, it is difficult to judge what the best reference states are by examining the original programs. In this study, we aim to address this issue and evaluate the reference states by a unified database and programming environment. We constructed distance‐specific atomic potentials using six widely‐used reference states based on 1022 high‐resolution protein structures, which are applied to rank modeling in six sets of structure decoys. The reference state on random‐walk chain outperforms others in three decoy sets while those using ideal‐gas, quasi‐chemical approximation and averaging sample stand out in one set separately. Nevertheless, the performance of the potentials relies on the origin of decoy generations and no reference state can clearly outperform others in all decoy sets. Further analysis reveals that the statistical potentials have a contradiction between the universality and pertinence, and optimal reference states should be extracted based on specific application environments and decoy spaces. Proteins 2012; © 2012 Wiley Periodicals, Inc.
Photoinduced fibrils formation of chicken egg white lysozyme under native conditions
Authors: Xie Jin‐Bing , Cao Yi , Pan Hai , Qin Meng , Yan Zhi‐Qiang , Xiong Xiang , Wang Wei 
Published: April 2013

AbstractRecent findings showed that transiently accessing structurally native‐like yet energetically higher conformational states is sufficient to trigger the formation of protein fibrils. Typically, these conformational states are made available through changing solvent conditions or introducing mutations. Here we show a novel way to initialize fibril formation for Chicken egg white lysozyme (CEWL) under native conditions via controlled UV illumination. Through a cassette of tryptophan‐based photochemistry, the two terminal disulfide bonds in CEWL can be selectively reduced. The reduced CEWL is then converted to conformational states with the C‐terminal fragment floppy upon thermal fluctuation. These states serve as precursors for the fibrillar aggregation. Intriguingly, the CEWL fibrils are stabilized by intermolecular disulfide bonds instead of noncovalent β‐sheet structures, distinct from the amyloid‐like lysozyme fibrils reported before. Based on the experimental evidences and all‐atom molecular dynamics simulation, we proposed a “runaway domain‐swapping” model for the structure of the CEWL fibrils, in which each CEWL molecule swaps the C‐terminal fragment into the complementary position of the adjacent molecule along the fibrils. We anticipate that this fibrillation mechanism can be extended to many other disulfide‐containing proteins. Our study stands for the first example of formation of protein fibrils under native conditions upon UV illumination and poses the potential danger of low UV dose to organisms at the protein level. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Design of human granzyme B variants resistant to serpin B9
Authors: Losasso Valeria , Schiffer Sonja , Barth Stefan , Carloni Paolo 
Published: April 2013

AbstractHuman granzyme B (hGB) is a serine protease involved in immune‐mediated apoptosis. Its cytotoxicity makes it potentially applicable in cancer therapy. However, the effectiveness of hGB can be hampered by the cytosolic expression of a natural protein inhibitor, human Serpin B9 (hSB9). Here, we used computational approaches to identify hGB mutations that can affect its binding to hSB9 without significantly decreasing its catalytic efficiency. Alanine‐scanning calculations allowed us to identify residues of hGB important for the interaction with hSB9. Some variants were selected, and molecular dynamic simulations on the mutated hGB in complex with hSB9 in aqueous solution were carried out to investigate the effect of these variants on the stability of the complex. The R28K, R201A, and R201K mutants significantly destabilized the interaction of the protein with hSB9. Consistently, all of these variants also retained their activity in the presence of the Serpin B9 inhibitor in subsequent in vitro assays of wild‐type and mutated hGB. In particular, the activity of R201K hGB with and without Serpin B9 is very similar to that of the wild‐type protein. Hence, R201K hGB emerges as a promising species for antitumoral therapy applications. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Solution structure of FK506‐binding protein 12 from Aedes aegypti
Authors: Chakraborty Goutam , Shin Joon , Nguyen Quoc Toan , Harikishore Amaravadhi , Baek Kwanghee , Yoon Ho Sup 
Published: April 2013

AbstractDengue remains one of the major public concerns as the virus eludes the immune response. Currently, no vaccines or antiviral therapeutics are available for dengue prevention or treatment. Immunosuppressive drug FK506 shows an antimalarial activity, and its molecular target, FK506‐binding protein (FKBP), was identified in human Plasmodium parasites. Likewise, a conserved FKBP family protein has also been identified in Aedes aegypti (AaFKBP12), which is expected to play a similar role in the life cycle of Aedes aegypti, the primary vector of dengue virus infection. As FKBPs belong to a highly conserved class of immunophilin family and are involved in key biological regulations, they are considered as attractive pharmacological targets. In this study, we have determined the nuclear magnetic resonance solution structure of AaFKBP12, a novel FKBP member from Aedes aegypti, and presented its structural features, which may facilitate the design of potential inhibitory ligands against the dengue‐transmitting mosquitoes. Proteins 2012;. © 2012 Wiley Periodicals, Inc.
Predicting Ca2+‐binding sites using refined carbon clusters
Authors: Zhao Kun , Wang Xue , Wong Hing C. , Wohlhueter Robert , Kirberger Michael P. , Chen Guantao , Yang Jenny J. 
Published: April 2013

AbstractIdentifying Ca2+‐binding sites in proteins is the first step toward understanding the molecular basis of diseases related to Ca2+‐binding proteins. Currently, these sites are identified in structures either through X‐ray crystallography or NMR analysis. However, Ca2+‐binding sites are not always visible in X‐ray structures due to flexibility in the binding region or low occupancy in a Ca2+‐binding site. Similarly, both Ca2+ and its ligand oxygens are not directly observed in NMR structures. To improve our ability to predict Ca2+‐binding sites in both X‐ray and NMR structures, we report a new graph theory algorithm (MUGC) to predict Ca2+‐binding sites. Using carbon atoms covalently bonded to the chelating oxygen atoms, and without explicit reference to side‐chain oxygen ligand co‐ordinates, MUGC is able to achieve 94% sensitivity with 76% selectivity on a dataset of X‐ray structures composed of 43 Ca2+‐binding proteins. Additionally, prediction of Ca2+‐binding sites in NMR structures was obtained by MUGC using a different set of parameters, which were determined by the analysis of both Ca2+‐constrained and unconstrained Ca2+‐loaded structures derived from NMR data. MUGC identified 20 of 21 Ca2+‐binding sites in NMR structures inferred without the use of Ca2+ constraints. MUGC predictions are also highly selective for Ca2+‐binding sites as analyses of binding sites for Mg2+, Zn2+, and Pb2+ were not identified as Ca2+‐binding sites. These results indicate that the geometric arrangement of the second‐shell carbon cluster is sufficient not only for accurate identification of Ca2+‐binding sites in NMR and X‐ray structures but also for selective differentiation between Ca2+ and other relevant divalent cations. © Proteins 2012. © 2012 Wiley Periodicals, Inc.
Nucleation‐based prediction of the protein folding rate and its correlation with the folding nucleus size
Authors: Galzitskaya Oxana V. , Glyakina Anna V. 
Published: April 2013

AbstractThe problem of protein self‐organization is in the focus of current molecular biology studies. Although the general principles are understood, many details remain unclear. Specifically, protein folding rates are of interest because they dictate the rate of protein aggregation which underlies many human diseases. Here we offer predictions of protein folding rates and their correlation with folding nucleus sizes. We calculated free energies of the transition state and sizes of folding nuclei for 84 proteins and peptides whose other parameters were measured at the point of thermodynamic equilibrium between their unfolded and native states. We used the dynamic programming method where each residue was considered to be either as folded as in its native state or completely disordered. The calculated and measured folding rates showed a good correlation at the temperature mid‐transition point (the correlation coefficient was 0.75). Also, we pioneered in demonstrating a moderate (‐0.57) correlation coefficient between the calculated sizes of folding nuclei and the folding rates. Predictions made by different methods were compared. The established good correlation between the estimated free energy barrier and the experimentally found folding rate of each studied protein/peptide indicates that our model gives reliable results for the considered data set. Proteins 2012; © 2012 Wiley Periodicals, Inc.
In silico structure–function analysis of E. cloacae nitroreductase
Authors: Isayev Olexandr , Crespo‐Hernández Carlos E. , Gorb Leonid , Hill Frances C. , Leszczynski Jerzy 
Published: April 2013

AbstractReduction, catalyzed by the bacterial nitroreductases, is the quintessential first step in the biodegradation of a variety of nitroaromatic compounds from contaminated waters and soil. The Enterobacter cloacae nitroreductase (EcNR) enzyme is considered as a prospective biotechnological tool for bioremediation of hazardous nitroaromatic compounds. Using diverse computational methods, we obtain insights into the structural basis of activity and mechanism of its function. We have performed molecular dynamics simulation of EcNR in three different states (free EcNR in oxidized form, fully reduced EcNR with benzoate inhibitor and fully reduced EcNR with nitrobenzene) in explicit solvent and with full electrostatics. Principal Component Analysis (PCA) of the variance‐covariance matrix showed that the complexed nitroreductase becomes more flexible overall upon complexation, particularly helix H6, in the vicinity of the binding site. A multiple sequence alignment was also constructed in order to examine positional constraints on substitution in EcNR. Five regions which are highly conserved within the flavin mononucleotide (FMN) binding site were identified. Obtained results and their implications for EcNR functioning are discussed, and new plausible mechanism has been proposed. Proteins 2012; © 2012 Wiley Periodicals, Inc.
Flexible connection of the N‐terminal domain in ClpB modulates substrate binding and the aggregate reactivation efficiency
Authors: Zhang Ting , Ploetz Elizabeth A. , Nagy Maria , Doyle Shannon M. , Wickner Sue , Smith Paul E. , Zolkiewski Michal 
Published: April 2013

AbstractClpB reactivates aggregated proteins in cooperation with DnaK/J. The ClpB monomer contains two nucleotide‐binding domains (D1, D2), a coiled‐coil domain, and an N‐terminal domain attached to D1 with a 17‐residue‐long unstructured linker containing a Gly‐Gly motif. The ClpB‐mediated protein disaggregation is linked to translocation of substrates through the central channel in the hexameric ClpB, but the events preceding the translocation are poorly understood. The N‐terminal domains form a ring surrounding the entrance to the channel and contribute to the aggregate binding. It was suggested that the N‐terminal domain's mobility that is maintained by the unstructured linker might control the efficiency of aggregate reactivation. We produced seven variants of ClpB with modified sequence of the N‐terminal linker. To increase the linker's conformational flexibility, we inserted up to four Gly next to the GG motif. To decrease the linker's flexibility, we deleted the GG motif and converted it into GP and PP. We found that none of the linker modifications inhibited the basal ClpB ATPase activity or its capability to form oligomers. However, the modified linker ClpB variants showed lower reactivation rates for aggregated glucose‐6‐phosphate dehydrogenase and firefly luciferase and a lower aggregate‐binding efficiency than wt ClpB. We conclude that the linker does not merely connect the N‐terminal domain, but it supports the chaperone activity of ClpB by contributing to the efficiency of aggregate binding and disaggregation. Moreover, our results suggest that selective pressure on the linker sequence may be crucial for maintaining the optimal efficiency of aggregate reactivation by ClpB. Proteins 2012; © 2012 Wiley Periodicals, Inc.
Adaptive fault‐tolerant backstepping control against actuator gain faults and its applications to an aircraft longitudinal motion dynamics
Authors: Shen Qikun , Jiang Bin , Cocquempot Vincent 
Published: April 2013

SUMMARYThe problem of fault‐tolerant control (FTC) for a class of uncertain nonlinear systems with actuator faults is discussed, and an observer‐based FTC scheme is proposed. Adaptive fuzzy observers are designed to provide a bank of residuals for fault detection and isolation. Using a backstepping approach, we proposed a novel fault diagnosis algorithm, which removes the classical assumption that the time derivative of the output error should be known. Further, an accommodation scheme is proposed to compensate for the effect of the fault, where it is not needed to know the bounds of the time derivative of the fault. The proposed controller guarantees that all signals of the closed‐loop system are semi‐globally uniformly ultimately bounded and converge to a small neighborhood of the origin by appropriately choosing designed parameters. In addition, a sufficient condition for the existence of an fault detection and isolation observer is derived using Lyapunov stability theory. Finally, a numerical example and a practical aircraft longitudinal motion dynamics are used to demonstrate the effectiveness of the proposed FTC approach. Copyright © 2013 John Wiley & Sons, Ltd.
The solution space geometry of random linear equations
Authors: Achlioptas Dimitris , Molloy Michael 
Published: April 2013

AbstractWe consider random systems of linear equations over GF(2) in which every equation binds k variables. We obtain a precise description of the clustering of solutions in such systems. In particular, we prove that with probability that tends to 1 as the number of variables, n, grows: for every pair of solutions σ,τ, either there exists a sequence of solutions starting at σ and ending at τ such that successive solutions have Hamming distance O(log n), or every sequence of solutions starting at σ and ending at τ contains a pair of successive solutions with distance Ω(n). Furthermore, we determine precisely which pairs of solutions are in each category. Key to our results is establishing the following high probability property of cores of random hypergraphs which is of independent interest. Every vertex not in the r‐core of a random k‐uniform hypergraph can be removed by a sequence of O(log n) steps, where each step amounts to removing one vertex of degree strictly less than r at the time of removal. © 2013 Wiley Periodicals, Inc. Random Struct. Alg., 46, 197–231, 2015
Refined quicksort asymptotics
Authors: Neininger Ralph 
Published: April 2013

AbstractThe complexity of the Quicksort algorithm is usually measured by the number of key comparisons used during its execution. When operating on a list of n data, permuted uniformly at random, the appropriately normalized complexity Yn is known to converge almost surely to a non‐degenerate random limit Y. This assumes a natural embedding of all Yn on one probability space, e.g., via random binary search trees. In this note a central limit theorem for the error term in the latter almost sure convergence is shown:

urn:x-wiley:10429832:media:rsa20497:rsa20497-math-0001

where denotes a standard normal random variable. © 2013 Wiley Periodicals, Inc. Random Struct. Alg., 46, 346–361, 2015
In The Media: Expanding Students' Experience With Academic Vocabulary
Authors: McKeown Margaret G. , Crosson Amy C. , Artz Nancy J. , Sandora Cheryl , Beck Isabel L. 
Published: April 2013

AbstractHow can we supplement the limited time available for vocabulary instruction while motivating students to attend to the words they are learning? As a part of an academic word vocabulary intervention, we challenged sixth‐grade students to find their words in the world around them. This activity, In the Media, garnered responses from 51 of the 61 students involved in the intervention. Analysis of students' reading comprehension achievement showed that it was not just high‐achieving students who responded; rather the full range of achievement was represented. Analysis of pretest and posttest data revealed that students who found more words had the highest gains in the final assessment. Examples of students' encounters and where they found them are discussed. These examples suggest that students developed flexible knowledge of their words, as they were able to find them in uses beyond those taught and in related forms that had not been introduced.
Rapid FT‐NIR Analysis of Edible Oils for Total SFA, MUFA, PUFA, and Trans FA with Comparison to GC
Authors: Mossoba Magdi M. , Azizian Hormoz , Tyburczy Cynthia , Kramer John K. G. , Delmonte Pierluigi , Kia Ali‐Reza Fardin , Rader Jeanne I. 
Published: April 2013

AbstractDeclarations of the total content of trans fatty acids (FA) and saturated FA (SFA) are mandatory on food labels in the US and Canada. Gas chromatography (GC) has been the method of choice for the determination of FA composition. However, GC is time consuming and requires conversion of fats and oils to their FA methyl esters. In the present study, a recently published Fourier transform near‐infrared (FT‐NIR) spectroscopic procedure was applied to the rapid (<5 min) determination of total SFA, monounsaturated FA (MUFA), polyunsaturated FA (PUFA), and trans FA contents of 30 commercially available edible fats and oils. Good agreement was obtained between the GC and FT‐NIR methods for the determination of total SFA, MUFA, and PUFA contents. Differences between the two methods were apparent for the determination of trans fat at trans fat levels <2 % of total fat. The analytical determinations of total SFA, MUFA, and PUFA contents for many of the oils examined differed from the respective values declared on the product labels. Our findings demonstrate that the FT‐NIR procedure serves as a suitable alternative method for the rapid determination of total SFA, MUFA, PUFA and trans FA contents of neat vegetable oils.