bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐Resolution Floating Point Time Scale (FPTS) of the Permian Capitanian Stage in South China
Authors: Wu‐Qiang XUE , Bo LI , Jia‐Xin YAN , Ellwood Brooks B. , Tomkin Jonathan H. , Yan WANG , Zong‐Min ZHU
Published: February 2016

Here we present a magnetic susceptibility (χ) dataset from the Permian Capitanian strata exposed in the Tieqiao section, Laibin area, South China, a supplementary reference section for the Guadalupian‐Lopingian (Middle‐Upper Permian) Global Boundary Stratotype Section and Point (GSSP). The succession consists of alternating thin‐bedded chert with micritic limestone of basinal and slope facies, with a carbonate cap indicating shallow‐water platform deposition. χ datasets, which are mostly negative (diamagnetic), suggest that the Laibin area was isolated from terrigenous sources during most of the Capitanian. A sudden increase in the χ signal just below the Guadalupian‐Lopingian (G‐L) boundary is recorded. Although regression at the terminal Capitanian might have contributed to the increase, the coincidence of the increase with the onset of the Emeishan Large Igneous Province (LIP) eruptions demonstrate pronounced volcanic effects controlling χ in this part of the section. χ and thermomagnetic susceptibility measurements indicate that the dominant magnetic constituents in this study are diamagnetic calcite and chert, with subordinate paramagnetic and ferrimagnetic minerals, derived from eolian and volcanic sources, and producing the cyclicity observed in the dataset.

Spectral (time‐series) analyses of χ data were performed using Multi Taper Method (MTM) and Fourier Transform (FT) analysis. Five frequencies that are consistent with Milankovitch‐band orbital forcing were compared to the dataset: eccentricity E1 and E2 (100 and 405 ka, respectively), obliquity O2 (44.10 ka), and precession P1 (17.70 ka) and P2 (20.95 ka). Interpretation of these results indicates that the duration for the Capitanian in the Tieqiao section was ∼3.85 Ma. Likewise, the mean sediment accumulation rate (SAR) for the whole Capitanian was ∼2.91 cm·ka−1. In addition, graphic comparison of the Tieqiao χ data to a floating point time scale for Upper Wordian through Capitanian time allows estimates of the duration for conodont zones identified from the section; these ranging from 26.6 ka to 2.3 Ma before extinction of individual conodont species. Therefore, timing of the onset age of Emeishan LIP eruptions is estimated to yield an age of 262.7 Ma, with placement of these eruptions at 1.4 Ma below the G‐L boundary.
Strategy and Application of Waveform Inversion Based on Seismic Data Subset
Authors: Liang‐Guo DONG , Chao HUANG , Ben‐Xin CHI , Yu‐Zhu LIU
Published: February 2016

The main difficulty in seismic full waveform inversion (FWI) is the strong nonlinearity, which is caused by the complexity of seismic wave propagation. Different components of elastic parameters result in different characteristics in seismic data. Meanwhile, different inversion quality is required in different stages of exploration or exploitation. So, there is no need to pursue matching all the seismic information during the inversion. Some problems can be solved by matching part of seismic information and the strong nonlinearity can also be avoided by this way. According to this consideration, a generalized FWI strategy and method based on seismic data subsets is presented. For different seismic data subsets, the gradients of the misfits have the same form and can be calculated by two times of seismic wave forward modeling just as traditional FWI. The only difference in calculating the gradients is the adjoint source. During the waveform inversion based on seismic data subsets, the responses of seismic data to different scales of perturbation on different media parameters should be analyzed intensively. Different seismic data subsets should be used in different stages of full waveform inversion. And then the residual of this seismic data subset is back‐projected along the reasonable sub‐kernels to decide where and which component of the model parameter need to be updated. As examples, envelope and reflection data subsets are used in FWI with synthetic and practical data to prove the validity and effectiveness of our presented FWI strategy and method. Especially, in the absence of low frequency contents, reasonable misfits can be used to recover the background compressional and shear velocity models using these FWI methods.
Terrain Correction in the Gradient Calculation of Spontaneous Potential Data
Authors: Jun‐Heng WANG , Yu GENG
Published: February 2016

Terrain correction is to eliminate the effect of terrain relief around measurement points on observation results in gravitational and geoelectrical prospecting. Because the microscopic mechanism of spontaneous potential anomalies formed by terrains is rather complex, it is difficult to obtain an analytic formula, whereas a more intuitive method can be adopted instead to find out the fitting formula between these two variables. According to the study, in spontaneous potential gradient calculation, spontaneous potential anomalies caused by topography can be divided into two types: one is that anomalies have a mirror‐image relation with terrain relief, which accounts for the majority of cases; the other one is that anomalies have an inverted mirror‐image relation with terrain relief. The relation between a majority of anomalies and terrain relief could be linear, quadratic or exponential, among which linear relation is the primary. As for which fitting relation should be adopted specifically, it can be decided by selecting a typical terrain and spontaneous potential curve first and judging through the law of variations; and trial calculation method can be adopted as well to choose the appropriate fitting formula by comparing the correction effects.

The Ordos Basin was selected to be the research site in this paper and the terrain correction method which is applicable to spontaneous potential gradient calculation was put forward. Through the comparison of the correction results of three kinds of fitting formulas, it was concluded that the linear fitting formula can better describe the relationship between relative height and spontaneous potential correction amount in the surveyed area. Terrain correction can effectively eliminate the correlation between relative height and spontaneous potential. The corrected spontaneous potential curves can reflect subsurface geological structure better, and the anomalies showed by the spontaneous potential contour map can be more prominent. Terrain relief can influence the appearance of anomalies in spontaneous potential gradient calculation, especially when the area of rugged terrain is comparable to the area of target geological bodies, which may make it difficult to distinguish these two anomalies. Thus the study on terrain correction has great importance in practice.
Improvement of the Ray‐Tracing Based Method for Calculating Hypocentral Loci for Earthquake Location
Authors: Ai‐Hua ZHAO , Zhi‐Feng DING , Zhi‐Ming BAI
Published: February 2016

Hypocentral loci are useful for reliable and visual earthquake location, but they can hardly be analytically expressed when the velocity model is complex. There is a ray‐tracing based numerical method to calculate them, in which a focal locus is represented in terms of ray paths from the minimum point (namely initial point) to low residual points (referred as hypocentral locus reference points, HLRPs) in its residual field. It has no restrictions on the complexity of the velocity model and can produce quite fine results. However, this method is incapable of addressing multi‐segment loci and inadequate for processing large quantity of data. Additionally, it is rather laborious and difficult to set its controlling parameters for obtaining both fine and complete hypocentral loci. In this study, we improve the ray‐tracing based numerical method to overcome its disadvantages: (1) HLRPs are selected from nodes of the model cells that the hypocentral locus goes through, by means of a so‐called peeling method. (2) The calculation domain of a hypocentral locus is defined as such a low residual area that its connected regions each include one segment of the locus and then all the focal locus segments are respectively calculated with the minimum traveltime tree algorithm for tracing rays by repeatedly assigning the minimal point among those HLRPs that have not been traced as an initial point. (3) Short ray paths without branching are removed to make the calculated locus finer. Numerical tests of virtual and real events show that the improved method is capable of efficiently calculating hypocentral loci with good completeness and fineness for earthquakes in a complex model.
Contrasting Phytoplankton Structure and Morphologically Based Functional Groups of Reservoirs That Differ in the Adjacent Surrounding
Authors: Wilk‐Woźniak Elżbieta , Koreivienė Judita , Karosienė Jūratė , Pociecha Agnieszka , Strzesak Magdalena , Mróz Wojciech
Published: February 2016

Increasing human activity has resulted in the transformation of waters and their landscape leading to fragmentation and degradation of natural ecosystems. We hypothesized that adjacent surrounding structures of water reservoir is weighty factor explaining changes in phytoplankton. The aim of the study was to find what level of identification is adequate to routine analyses and assess the best criteria that reflect structure of adjacent surrounding of reservoirs. Lithuanian and Polish reservoirs located in similar climatic conditions and of similar morphology were studied. The adjacent land use was described based on Corine Land Cover 2006. The physico‐chemical parameters of waters, structure and biomass of phytoplankton, Shannon index and obligatory autotrophic to mixotrophic species ratio were analyzed. The main difference between reservoirs was natural (Lithuanian reservoir: 67.8%) and agricultural landscape structure (Polish reservoir: 78.4%). Both ecosystems showed significant statistical differences in a few chemical features and in phytoplankton taxonomic and morphologically based functional groups (MBFG), Shannon index and autotrophic to mixotrophic species ratio. The dominant phytoplankton groups and MBFG better reflected stresses resulted differences of adjacent surrounding structure, compared with single species. In conclusion, the best criteria indicated the differences in the structure of adjacent surrounding of water ecosystems are MBFG and autotrophic to mixotrophic species ratio were presented.
Cationic gadolinium chelate for magnetic resonance imaging of cartilaginous defects
Authors: Nwe Kido , Huang Ching‐Hui , Qu Feini , Warden‐Rothman Robert , Zhang Clare Y. , Mauck Robert L. , Tsourkas Andrew
Published: February 2016

The ability to detect meniscus defects by magnetic resonance arthrography (MRA) can be highly variable. To improve the delineation of fine tears, we synthesized a cationic gadolinium complex, (Gd‐DOTA‐AM4)2+, that can electrostatically interact with Glycosaminoglycans (GAGs). The complex has a longitudinal relaxivity (r1) of 4.2 mM‐1s‐1 and is highly stable in serum. Its efficacy in highlighting soft tissue tears was evaluated in comparison to a clinically employed contrast agent (Magnevist) using explants obtained from adult bovine menisci. In all cases, Gd‐DOTA‐AM4 appeared to improve the ability to detect the soft tissue defect by providing increased signal intensity along the length of the tear. Magnevist shows a strong signal near the liquid‐meniscus interface, but much less contrast is observed within the defect at greater depths. This provides initial evidence that cationic contrast agents can be used to improve the diagnostic accuracy of MRA. Copyright © 2016 John Wiley & Sons, Ltd.
Use and effectiveness of quitlines versus Web‐based tobacco cessation interventions among 4 state tobacco control programs
Authors: Neri Antonio J. , Momin Behnoosh R. , Thompson Trevor D. , Kahende Jennifer , Zhang Lei , Puckett Mary C. , Stewart Sherri L.
Published: February 2016

BACKGROUND

Comparative effectiveness studies of state tobacco quitlines and Web‐based tobacco cessation interventions are limited. In 2009, the US Centers for Disease Control and Prevention undertook a study of the comparative effectiveness of state quitlines and Web‐based tobacco cessation interventions.

METHODS

Standardized questionnaires were administered to smokers who enrolled exclusively in either quitlines or Web‐based tobacco cessation services in 4 states in 2011‐2012. The primary outcome was the 30‐day point prevalence abstinence (PPA) rate at 7 months both between and within interventions.

RESULTS

A total of 4086 participants were included in the analysis. Quitline users were significantly older, more heterogeneous in terms of race and ethnicity, less educated, less likely to be employed, and more often single than Web‐based users. The 7‐month 30‐day PPA rate was 32% for quitline users and 27% for Web‐based users. Multivariate models comparing 30‐day PPA rates between interventions indicated that significantly increased odds of quitting were associated with being partnered, not living with another smoker, low baseline cigarette use, and more interactions with the intervention. After adjustments for demographic and tobacco use characteristics, quitline users had 1.26 the odds of being abstinent in comparison with Web‐based users (95% confidence interval, 1.00‐1.58; P = .053).

CONCLUSIONS

This is one of the largest comparative effectiveness studies of state tobacco cessation interventions to date. These findings will help public health agencies develop and tailor evidence‐based tobacco cessation programs. Further research should focus on users of Web‐based cessation interventions sponsored by state health departments and their cost‐effectiveness. Cancer 2016;122:1126–1133. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Effect of Sodium Dodecyl Sulfate Concentration on Supramolecular Gel Electrophoresis
Authors: Tazawa Shohei , Kobayashi Kazuhiro , Yamanaka Masamichi
Published: February 2016

Electrophoresis of denatured proteins was performed in a supramolecular hydrogel matrix constructed by the self‐assembly of amphiphilic tris‐urea 1 in the tris‐glycine‐sodium dodecyl sulfate (SDS) buffer. Proteins were separated based on two different molecular sieve effects in this electrophoretic method. Smaller proteins showed a larger mobility than larger proteins as in SDS‐PAGE with various large proteins. In contrast, smaller proteins showed a poorer mobility than larger proteins, similarly to gel filtration conducted for various small proteins. The dominant separation mode changes at a certain molecular weight of the protein and this threshold is influenced by the concentration of SDS.
Photochemistry of Wild‐Type and N378D Mutant E. coli DNA Photolyase with Oxidized FAD Cofactor Studied by Transient Absorption Spectroscopy
Authors: Müller Pavel , Brettel Klaus , Grama Laszlo , Nyitrai Miklos , Lukacs Andras
Published: February 2016

DNA photolyases (PLs) and evolutionarily related cryptochrome (CRY) blue‐light receptors form a widespread superfamily of flavoproteins involved in DNA photorepair and signaling functions. They share a flavin adenine dinucleotide (FAD) cofactor and an electron‐transfer (ET) chain composed typically of three tryptophan residues that connect the flavin to the protein surface. Four redox states of FAD are relevant for the various functions of PLs and CRYs: fully reduced FADH− (required for DNA photorepair), fully oxidized FADox (blue‐light‐absorbing dark state of CRYs), and the two semireduced radical states FAD.− and FADH. formed in ET reactions. The PL of Escherichia coli (EcPL) has been studied for a long time and is often used as a reference system; however, EcPL containing FADox has so far not been investigated on all relevant timescales. Herein, a detailed transient absorption study of EcPL on timescales from nanoseconds to seconds after excitation of FADox is presented. Wild‐type EcPL and its N378D mutant, in which the asparagine facing the N5 of the FAD isoalloxazine is replaced by aspartic acid, known to protonate FAD.− (formed by ET from the tryptophan chain) in plant CRYs in about 1.5 μs, are characterized. Surprisingly, the mutant protein does not show this protonation. Instead, FAD.− is converted in 3.3 μs into a state with spectral features that are different from both FADH. and FAD.−. Such a conversion does not occur in wild‐type EcPL. The chemical nature and formation mechanism of the atypical FAD radical in N378D mutant EcPL are discussed.
Towards Redox‐Driven Unidirectional Molecular Motion
Authors: Logtenberg Hella , Areephong Jetsuda , Bauer Jurica , Meetsma Auke , Feringa Ben L. , Browne Wesley R.
Published: February 2016

Redox‐driven molecular motion is an attractive alternative to light‐driven processes. Here, the ability of an overcrowded alkene‐based unimolecular light‐driven rotary motor (A) to be driven by oxidation/reduction cycles is explored. We show that two‐electron oxidation ofAis followed by irreversible deprotonation and reduction to form a monocationic speciesD+, in which the stereogenic center is lost. This latter species was isolated through preparative electrolysis and its structure was confirmed by using single‐crystal X‐ray analysis. However, at short timescales and in the absence of Brønsted acids, these processes can be outrun and the oxidation ofAto a dicationic speciesB2+occurs, in which the central double bond (the axle of the molecular motor) becomes a single bond; when followed by rapid reduction, it results in the reformation ofA, potentially in both its stable and unstable conformations. The latter conformation, if formed, undergoes thermal helix inversion, completing a rotary cycle. The data obtained regarding these reactions provide a window of opportunity for the motor to be driven electrochemically, without degradation from chemical reactions of the oxidized motor.
Assessment of the impact of scheduled postmarketing safety summary analyses on regulatory actions
Authors: Sekine S , Pinnow EE , Wu E , Kurtzig R , Hall M , Dal Pan GJ
Published: February 2016

In addition to standard postmarketing drug safety monitoring, Section 915 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) requires the US Food and Drug Administration (FDA) to conduct a summary analysis of adverse event reports to identify risks of a drug or biologic product 18 months after product approval, or after 10,000 patients have used the product, whichever is later. We assessed the extent to which these analyses identified new safety signals and resultant safety‐related label changes. Among 458 newly approved products, 300 were the subjects of a scheduled analysis; a new safety signal that resulted in a safety‐related label change was found for 11 of these products. Less than 2% of 713 safety‐related label changes were based on the scheduled analyses. Our study suggests that the safety summary analyses provide only marginal value over other pharmacovigilance activities.
Heteroacenes Bearing the Pyrimidine Scaffold: Synthesis, Photophysical and Electrochemical Properties
Authors: Verbitskiy Egor V. , Cheprakova Ekaterina M. , Makarova Nadezhda I. , Dorogan Igor V. , Metelitsa Anatoly V. , Minkin Vladimir I. , Slepukhin Pavel A. , Svalova Tatyana S. , Ivanova Alla V. , Kozitsina Alisa N. , Rusinov Gennady L. , Chupakhin Oleg N. , Charushin Valery N.
Published: February 2016

A convenient synthetic route to novel 7‐substituted benzo[f]thieno[3,2‐h]quinazoline and 8‐substituted benzo[g,h]dithieno[2,3‐e:3′,2′‐j]perimidine systems, bearing the fused pyrimidine ring, has been advanced. A commercially available 5‐bromopyrimidine was used as the starting material to obtain various polycyclic systems through the sequence of nucleophilic aromatic substitution of hydrogen (the SNH reaction), Suzuki cross‐coupling and oxidative photocyclization. Evidence for the structure of benzo[g,h]dithieno[2,3‐e:3′,2′‐j]perimidines has been obtained by X‐ray crystallographic analysis. Molecular orbital calculations (DFT), as well as redox and optical measurements for all new compounds have been performed. The data show that the reported polycyclic systems have potential for use in organic electronic applications.
Zn‐HZSM‐5 catalysts for methane dehydroaromatization
Authors: Lai Yungchieh , Veser Götz
Published: February 2016

The nature of the active species in Zn‐containing HZSM‐5 catalysts was investigated by preparing Zn‐HZSM‐5 via three different synthetic approaches: wet ion exchange, wet impregnation, and core–shell synthesis. By investigating the impact of the preparation methods on the distribution of Zn species, and studying the catalytic performance of the resulting materials in methane dehydroaromatization (DHA), it was shown that metallic Zn0 nanoclusters inside the zeolite micropore constituted the most active species for DHA, but get irreversible loss from the catalyst via evaporation at the high‐temperature conditions of DHA. In contrast, Zn2+ anchored at the exchange sites of the zeolite were the most stable species, but provided little to no aromatization activity. As a result, and counter to previous reports in the literature, it was concluded that Zn/HZSM‐5 was not a suitable catalyst for non‐oxidative methane dehydroaromatization. Nonetheless, the study confirmed that well‐dispersed metal species inside the zeolitic micropores were critical for aromatization activity of zeolite‐based catalysts. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 334–344, 2016
A comprehensive review on selective catalytic reduction catalysts for NOx emission abatement from municipal solid waste incinerators
Authors: Yan Qinghua , Yang Ruoyan , Zhang Yili , Umar Ahmad , Huang Zhanggen , Wang Qiang
Published: February 2016

Incineration is considered to be an effective disposal method for municipal solid wastes (MSW), which is attracting increasing attention due to its great performance in waste reduction. However, one big problem for incineration process is the release of a number of harmful pollutants. Nitrogen oxide (NOx) is one of the major pollutants in the exhaust of various combustion processes because it is harmful to both environment and human health. For reducing NOx emission from MSW incinerators flue gases, selective catalytic reduction (SCR) technology has been widely investigated because of its high efficiency, good selectivity, and low cost. Since the gas composition from MSW incinerators is more complex than that from coal‐fired power plants, lots of attention has been paid to making more robust SCR catalysts. The aim of this article is to provide a critical and timely review on the recent progresses of SCR catalysts used for MSW incinerator flue gases. We also discussed the influence of HCl, SO2, alkali metal, phosphorus, arsenic, lead, and so forth on the conversion of NOx to N2. Moreover, the mechanism and kinetics involved in the SCR of NOx for MSW incinerator flue gases were also discussed. We hope this contribution could shed light on the development of novel catalysts and/or technologies from MSW incinerators flue gases. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 1061–1069, 2016
Computational meta‐analysis of statistical parametric maps in major depression
Authors: Arnone Danilo , Job Dominic , Selvaraj Sudhakar , Abe Osamu , Amico Francesco , Cheng Yuqi , Colloby Sean J. , O'Brien John T. , Frodl Thomas , Gotlib Ian H. , Ham Byung-Joo , Kim M Justin , Koolschijn P Cédric MP , Périco Cintia A.‐M. , Salvadore Giacomo , Thomas Alan J. , Van Tol Marie‐José , van der Wee Nic J.A. , Veltman Dick J. , Wagner Gerd , McIntosh Andrew M.
Published: February 2016

Objective

Several neuroimaging meta‐analyses have summarized structural brain changes in major depression using coordinate‐based methods. These methods might be biased toward brain regions where significant differences were found in the original studies. In this study, a novel voxel‐based technique is implemented that estimates and meta‐analyses between‐group differences in grey matter from individual MRI studies, which are then applied to the study of major depression.

Methods

A systematic review and meta‐analysis of voxel‐based morphometry studies were conducted comparing participants with major depression and healthy controls by using statistical parametric maps. Summary effect sizes were computed correcting for multiple comparisons at the voxel level. Publication bias and heterogeneity were also estimated and the excess of heterogeneity was investigated with metaregression analyses.

Results

Patients with major depression were characterized by diffuse bilateral grey matter loss in ventrolateral and ventromedial frontal systems extending into temporal gyri compared to healthy controls. Grey matter reduction was also detected in the right parahippocampal and fusiform gyri, hippocampus, and bilateral thalamus. Other areas included parietal lobes and cerebellum. There was no evidence of statistically significant publication bias or heterogeneity.

Conclusions

The novel computational meta‐analytic approach used in this study identified extensive grey matter loss in key brain regions implicated in emotion generation and regulation. Results are not biased toward the findings of the original studies because they include all available imaging data, irrespective of statistically significant regions, resulting in enhanced detection of additional areas of grey matter loss. Hum Brain Mapp 37:1393‐1404, 2016. © 2016 Wiley Periodicals, Inc.
Squamous cell cancer of the nasal cavity: New insights and implications for diagnosis and treatment
Authors: Becker Christoph , Kayser Gian , Pfeiffer Jens
Published: February 2016

Background

Squamous cell carcinoma (SCC) of the nasal cavity is a rare malignancy and often analyzed in heterogeneous studies with other tumors of the nose or the paranasal sinuses. The purpose of this study was to evaluate distinct risk factors, tumor characteristics, outcome predictors, and the prevalence of human papillomavirus (HPV) in SCC of the nasal cavity.

Methods

We conducted a retrospective study of 39 patients treated at a single quaternary medical care and cancer center. We analyzed tumor characteristics, HPV status, treatment, and outcome. We present the largest study on SCC of the nasal cavity from a single center.

Results

The majority of patients (70.2%) presented with an early‐stage tumor (T1 or T2). Only 1 patient had a single neck metastasis at the time of diagnosis. Four tumors were HPV‐positive. Most patients (61.5%) underwent surgical resection without adjuvant treatment, with 12 patients (30.8%) undergoing additional radiotherapy. Three patients were treated with primary radiotherapy or chemoradiotherapy. No patient treated primarily with total rhinectomy developed local tumor recurrence.

Conclusion

Local tumor control is crucial, even if it makes radical surgery necessary. Postoperative epithetic treatment enables reliable follow‐up examinations. Regional metastases at the time of diagnosis are rare. Neck dissection should therefore be reserved for cases of suspected metastasis. HPV may also play a role in the etiology of SCC of the nasal cavity. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2112–E2117, 2016
Retreatment with sofosbuvir and simeprevir of patients with hepatitis C virus genotype 1 or 4 who previously failed a daclatasvir‐containing regimen
Authors: Hézode Christophe , Chevaliez Stéphane , Scoazec Giovanna , Soulier Alexandre , Varaut Anne , Bouvier‐Alias Magali , Ruiz Isaac , Roudot‐Thoraval Françoise , Mallat Ariane , Féray Cyrille , Pawlotsky Jean‐Michel
Published: February 2016

Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct‐acting antiviral‐based regimens is commonly associated with emergence of resistance‐associated variants (RAVs). To avoid cross‐resistance, recent guidelines recommend that patients who have failed on nonstructural protein 5A (NS5A) inhibitors should be retreated with sofosbuvir (SOF; NS5B inhibitor) combined with simeprevir (SIM; protease inhibitor [PI]); however, supporting evidence is lacking. This “real‐world” study comprised patients who had failed to achieve SVR on previous NS5A‐based therapy with daclatasvir (DCV) plus pegylated interferon (Peg‐IFN) and ribavirin (RBV), with (n = 3) or without (n = 13) asunaprevir (ASV; PI). All 16 patients were retreated for 12 weeks with SOF plus SIM, without RBV. Antiviral efficacy was evaluated using the primary endpoint of SVR12 (SVR 12 weeks post‐treatment); on‐treatment response was also assessed. Patients (N = 16; 13 male; mean age: 54 years [range, 43‐73]) were chronically infected with HCV genotype (GT) 1 (1a, n = 11; 1b, n = 3) or 4 (n = 2); they had advanced fibrosis or compensated cirrhosis (FibroScan, 9.6‐70 kPa; cirrhosis, n = 9); median baseline HCV‐RNA level was 1.38 × 106 IU/mL. No patient discontinued treatment because of adverse events or virological failure. All patients achieved HCV RNA below lower limit of quantification (<12 IU/mL) by end of treatment (EOT) and 10 of 16 had a rapid response (week 4). SVR12 was achieved by 14 of 16 patients; the remaining 2 relapsed by 4 weeks post‐EOT (both were GT 1a infected with cirrhosis; 1 had previously failed DCV‐ASV plus Peg‐IFN and RBV). Presence of SIM RAVs/polymorphisms (R155K and Q80K) at study baseline did not predict retreatment failure. Conclusion: Our findings support the concept of retreating NS5A inhibitor failures with SOF combined with SIM. However, the most difficult‐to‐cure patients may need more than 12 weeks of treatment and/or the addition of RBV. (Hepatology 2016;63:1809‐1816)
Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver
Authors: Ku Nam‐On , Strnad Pavel , Bantel Heike , Omary M. Bishr
Published: February 2016

Keratins, formerly known as cytokeratins, are the major epithelial‐specific subgroup of intermediate filament proteins. Adult hepatocytes express keratin polypeptides 8 and 18 (K8/K18), whereas cholangiocytes express K8/K18 and keratins 7 and 19 (K7/K19). Keratins function primarily to protect hepatocytes from apoptosis and necrosis, which was revealed using several genetic mouse models. This cytoprotective function was further clarified by the identification of natural human keratin variants that are normally silent, but become pathogenic by predisposing their carriers to apoptosis during acute or chronic liver injury mediated by toxins, virus infection, or metabolic stress. During apoptosis, caspases cleave K18 and K19 at conserved aspartates (human K18/K19: 235Val‐Glu‐Val‐Asp↓) and K18 at a unique aspartate (human K18: 394Asp‐Ala‐Leu‐Asp↓), with the latter exposed epitope becoming recognized by the M30 antibody in blood and tissues. Additional K18‐containing protein backbone epitopes are detected using the M6 and M5 (termed M65) antibodies. Intact K18 and its associated fragments, which are released into blood during apoptosis and necrosis in various diseases, have been analyzed by enzyme‐linked immunosorbent assay using the M30/M65 antibodies or their signal ratios. Furthermore, M30/M65 levels have been used as diagnostic and prognostic biomarkers in acute and chronic liver diseases, including nonalcoholic steatohepatitis and acute liver failure. Other keratin biomarkers include K8/K18/K19‐related tissue polypeptide antigen, K18‐related tissue polypeptide‐specific antigen, and K19‐related CYFRA‐21‐1, which have been evaluated mostly in patients with epithelial tumors. Conclusion: Keratins and their fragments are released into blood during liver and other epithelial tissue injury. The epithelial specificity of K18/K19, epitope unmasking upon caspase digestion, keratin abundance, and relative keratin stability render them useful biomarkers for hepatocyte and cholangiocyte apoptosis and necrosis. However, the precise biochemical nature and release mechanism of circulating keratins remain unknown. (Hepatology 2016;64:966‐976)
Overexpression of BCLXL in Osteoblasts Inhibits Osteoblast Apoptosis and Increases Bone Volume and Strength
Authors: Moriishi Takeshi , Fukuyama Ryo , Miyazaki Toshihiro , Furuichi Tatsuya , Ito Masako , Komori Toshihisa
Published: February 2016

The Bcl2 family proteins, Bcl2 and BclXL, suppress apoptosis by preventing the release of caspase activators from mitochondria through the inhibition of Bax subfamily proteins. We reported that BCL2 overexpression in osteoblasts using the 2.3 kb Col1a1 promoter increased osteoblast proliferation, failed to reduce osteoblast apoptosis, inhibited osteoblast maturation, and reduced the number of osteocyte processes, leading to massive osteocyte death. We generated BCLXL (BCL2L1) transgenic mice using the same promoter to investigate BCLXL functions in bone development and maintenance. Bone mineral density in the trabecular bone of femurs was increased, whereas that in the cortical bone was similar to that in wild-type mice. Osteocyte process formation was unaffected and bone structures were similar to those in wild-type mice. A micro-CT analysis showed that trabecular bone volume in femurs and vertebrae and the cortical thickness of femurs were increased. A dynamic bone histomorphometric analysis revealed that the mineralizing surface was larger in trabecular bone, and the bone-formation rate was increased in cortical bone. Serum osteocalcin but not TRAP5b was increased, BrdU-positive osteoblastic cell numbers were increased, TUNEL-positive osteoblastic cell numbers were reduced, and osteoblast marker gene expression was enhanced in BCLXL transgenic mice. The three-point bending test indicated that femurs were stronger in BCLXL transgenic mice than in wild-type mice. The frequency of TUNEL-positive primary osteoblasts was lower in BCLXL transgenic mice than in wild-type mice during cultivation, and osteoblast differentiation was enhanced but depended on cell density, indicating that enhanced differentiation was mainly owing to reduced apoptosis. Increased trabecular and cortical bone volumes were maintained during aging in male and female mice. These results indicate that BCLXL overexpression in osteoblasts increased the trabecular and cortical bone volumes with normal structures and maintained them majorly by preventing osteoblast apoptosis, implicating BCLXL as a therapeutic target of osteoporosis. © 2016 American Society for Bone and Mineral Research.
Nitric Oxide Prevents Mouse Embryonic Stem Cell Differentiation Through Regulation of Gene Expression, Cell Signaling, and Control of Cell Proliferation
Authors: Tapia‐Limonchi Rafael , Cahuana Gladys M. , Caballano‐Infantes Estefania , Salguero‐Aranda Carmen , Beltran‐Povea Amparo , Hitos Ana B. , Hmadcha Abdelkrim , Martin Franz , Soria Bernat , Bedoya Francisco J. , Tejedo Juan R.
Published: February 2016

Nitric oxide (NO) delays mouse embryonic stem cell (mESC) differentiation by regulating genes linked to pluripotency and differentiation. Nevertheless, no profound study has been conducted on cell differentiation regulation by this molecule through signaling on essential biological functions. We sought to demonstrate that NO positively regulates the pluripotency transcriptional core, enforcing changes in the chromatin structure, in addition to regulating cell proliferation, and signaling pathways with key roles in stemness. Culturing mESCs with 2 μM of the NO donor diethylenetriamine/NO (DETA/NO) in the absence of leukemia inhibitory factor (LIF) induced significant changes in the expression of 16 genes of the pluripotency transcriptional core. Furthermore, treatment with DETA/NO resulted in a high occupancy of activating H3K4me3 at the Oct4 and Nanog promoters and repressive H3K9me3 and H3k27me3 at the Brachyury promoter. Additionally, the activation of signaling pathways involved in pluripotency, such as Gsk3‐β/β‐catenin, was observed, in addition to activation of PI3 K/Akt, which is consistent with the protection of mESCs from cell death. Finally, a decrease in cell proliferation coincides with cell cycle arrest in G2/M. Our results provide novel insights into NO‐mediated gene regulation and cell proliferation and suggest that NO is necessary but not sufficient for the maintenance of pluripotency and the prevention of cell differentiation. J. Cell. Biochem. 117: 2078–2088, 2016. © 2016 Wiley Periodicals, Inc.
Micro‐coagulation effects on direct ultrafiltration of challenging raw river water
Authors: Ferrer Olga , Dekker Remon , Mesa Jose , Martín‐Alonso Jordi , Cortina José L , Gibert Oriol
Published: February 2016

BACKGROUND

The feasibility and competitiveness of substituting the conventional pre‐treatment of drinking water treatment plants (dioxichlorination, coagulation/flocculation, settling, sand filtration) by raw river water direct ultrafiltration (UF) was addressed.

RESULTS

A full scale UF module was operated continuously for 2 years, treating highly variable surface water. The sustainable hydraulic conditions leading to a greater water yield from the direct UF treatment scheme under different scenarios were defined. Summer periods enabled the attainment of higher filtration fluxes, although raw river water showed greater turbidity and total suspended solids content. Winter periods presented higher dissolved organic carbon concentration, with greater biopolymers content, which have been claimed as main membrane foulants. A preliminary micro‐coagulation of FeCl3 (<1.5 mg Fe(III) L−1) enabled supporting harsher hydraulic conditions and thus, implementing similar conditions throughout the year. Impacts of micro‐coagulation were more pronounced on filtration, particularly in winter, but a positive effect was also noticed in hydraulic and chemical cleaning stages, increasing the efficiency of the former and decreasing by half the frequency of the latter.

CONCLUSION

Direct UF proved to be competitive with the current conventional pre‐treatment, leading to a significant reduction in reagents needs and sludge production and an increased and more stable product water quality. © 2016 Society of Chemical Industry
Specimen preparation by ion beam slope cutting for characterization of ductile damage by scanning electron microscopy
Authors: Besserer Hans‐Bernward , Gerstein Gregory , Maier Hans Jürgen , Nürnberger Florian
Published: February 2016

To investigate ductile damage in parts made by cold sheet‐bulk metal forming a suited specimen preparation is required to observe the microstructure and defects such as voids by electron microscopy. By means of ion beam slope cutting both a targeted material removal can be applied and mechanical or thermal influences during preparation avoided. In combination with scanning electron microscopy this method allows to examine voids in the submicron range and thus to analyze early stages of ductile damage. In addition, a relief structure is formed by the selectivity of the ion bombardment, which depends on grain orientation and microstructural defects. The formation of these relief structures is studied using scanning electron microscopy and electron backscatter diffraction and the use of this side effect to interpret the microstructural mechanisms of voids formation by plastic deformation is discussed. A comprehensive investigation of the suitability of ion beam milling to analyze ductile damage is given at the examples of a ferritic deep drawing steel and a dual phase steel.Microsc. Res. Tech. 79:321–327, 2016. © 2016 Wiley Periodicals, Inc.
MR neurographic orthopantomogram: Ultrashort echo‐time imaging of mandibular bone and teeth complemented with high‐resolution morphological and functional MR neurography
Authors: Manoliu Andrei , Ho Michael , Nanz Daniel , Dappa Evelyn , Boss Andreas , Grodzki David M. , Liu Wei , Chhabra Avneesh , Andreisek Gustav , Kuhn Felix P.
Published: February 2016

Purpose

Panoramical radiographs or cone‐beam computed tomography (CT) are the standard‐of‐care in dental imaging to assess teeth, mandible, and mandibular canal pathologies, but do not allow assessment of the inferior alveolar nerve itself nor of its branches. We propose a new technique for “MR neurographic orthopantomograms” exploiting ultrashort echo‐time (UTE) imaging of bone and teeth complemented with high‐resolution morphological and functional MR neurography.

Materials and Methods

The Institutional Review Board approved the study in 10 healthy volunteers. Imaging of the subjects mandibles at 3.0T (Magnetom Skyra, Siemens‐Healthcare) using a 64‐channel head coil with isotropic spatial resolution for subsequent multiplanar reformatting, was performed. Bone images were acquired using a 3D PETRA sequence (TE, 0.07 msec). Morphological nerve imaging was performed using a dedicated 3D PSIF and 3D SPACE STIR sequence. Functional MR neurography was accomplished using a new accelerated diffusion‐tensor‐imaging (DTI) prototype sequence (2D SMS‐accelerated RESOLVE). Qualitative and quantitative image analysis was performed and descriptive statistics are provided.

Results

Image acquisition and subsequent postprocessing into the MR neurographic orthopantomogram by overlay of morphological and functional images were feasible in all 10 volunteers without artifacts. All mandibular bones and mandibular nerves were assessable and considered normal. Fiber tractography with quantitative evaluation of physiological diffusion properties of mandibular nerves yielded the following mean ± SD values: fractional anisotropy, 0.43 ± 0.07; mean diffusivity (mm2/s), 0.0014 ± 0.0002; axial diffusivity, 0.0020 ± 0.0002, and radial diffusivity, 0.0011 ± 0.0001.

Conclusion

The proposed technique of MR neurographic orthopantomogram exploiting UTE imaging complemented with high‐resolution morphological and functional MR neurography was feasible and allowed comprehensive assessment of osseous texture and neural microarchitecture in a single examination. J. Magn. Reson. Imaging 2016;44:393–400.
Determination of azithromycin residue in pork using a molecularly imprinted monolithic microcolumn coupled to liquid chromatography with tandem mass spectrometry
Authors: Zhou Tong , Yang Haicui , Jin Zhen , Liu Qingying , Song Xuqin , He Limin , Fang Binghu , Meng Chenying
Published: February 2016

Using spiramycin as a dummy template, a molecularly imprinted polymer monolithic micro‐column with high selection to azithromycin was prepared in a micropipette tip. The imprinting factor of the monolithic micro‐column prepared was approximately 2.67 and the morphological structure of the polymers was characterized by scanning electron microscopy. A simple, sensitive, and reproducible method based on the imprinted monolithic micro‐column coupled to liquid chromatography with tandem mass spectrometry was developed for determining the residues of azithromycin in pork. Pork samples were extracted with acetonitrile, cleaned up under the optimal monolithic micro‐column conditions, and analyzed using liquid chromatography with tandem mass spectrometry in the multiple reaction monitoring mode. The assay exhibited a linear dynamic range of 0.50–50 μg/L with the correlation coefficient (r2) above 0.99. In the three spiking levels of 0.50, 1.0, and 10 μg/kg, the average recoveries of azithromycin from pork samples were between 85.8 and 96.5% with a relative standard deviation below 10%. The limit of detection and limit of quantitation were 0.03 and 0.1 μg/kg, respectively.
Dilution reveals how viral lysis and grazing shape microbial communities
Authors: Cram Jacob A. , Parada Alma E. , Fuhrman Jed A.
Published: February 2016

Grazing by protists and viral infection are the main known sources of marine bacterial mortality, and both processes shape the structure and ecology of microbial communities. We diluted planktonic microbial communities to determine how decreasing the encounter rate between bacteria, grazers, and viruses affects community structure. In experimental treatments, sea water was diluted 10‐fold in water from which protists and bacteria had been removed (0.2 μm filtered), or from which protists bacteria and viruses had been removed (0.02 μm filtered). In both dilution treatments, bacterial and protistan communities generally recovered within 3 d to near their original abundances, but viruses did not. The microbial community structure of bacteria in both diluted treatments was significantly different from untreated control communities, after 3 d, and significantly different between the 0.2 μm and 0.02 μm dilution treatments after 6 d. Diluted treatments were dominated by operational taxonomic units that are normally rare in near‐surface seawater, including some normally more abundant in the deep water at this location such as SAR324 and SAR406, while abundant surface taxa including SAR11 did not increase in abundance after dilution. These results are consistent with the hypothesis that microbes face a tradeoff between fast growth and resistance to predation and infection, and that microbes that are normally most abundant in the California coastal surface waters (such as SAR11 and Actinobacteria) are both more grazer resistant and slower growing than potentially opportunistic organisms that are rare in surface water but capable of fast net growth when grazers or viruses are removed.
Exploring the Compositional Heterogeneity of Vis‐Broken Impact Poly(propylene) Copolymers by Advanced Fractionation Methods
Authors: Phiri Mohau Justice , Pasch Harald
Published: February 2016

Vis‐breaking or rheology control is an important technical process to improve the processability of impact poly(propylene) copolymers (IPCs). In the vis‐breaking process the molar mass and its dispersity are reduced and the crystallinity changes and polar carbonyl functionalities are introduced due to the reaction of the polymer with peroxide. Although the fundamental principles of vis‐breaking are well understood, not much research has been devoted to the investigation of the molecular changes brought about by the vis‐breaking process. In the present study, the effect of vis‐breaking on the molecular parameters of IPCs is elucidated using advanced fractionation methods. After the analysis of the bulk sample properties, the samples are fractionated using preparative temperature rising elution fractionation and the fractions are analyzed by Fourier transform infrared spectroscopy, differential scanning calorimetry, crystallization analysis fractionation, and high temperature high performance liquid chromatography techniques. For the first time, an effective multidimensional analytical approach is established to study compositional heterogeneities in vis‐broken IPC materials.

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Local strong solutions to a compressible non‐Newtonian fluid with density‐dependent viscosity
Authors: Fang Li , Guo Zhenhua , Wang Yuxin
Published: February 2016

We consider the initial boundary problem for a compressible non‐Newtonian fluid with density‐dependent viscosity. The local existence of strong solution is established that is based on some compatibility condition. Moreover, it is also proved that the solutions are to blow up, and the maximum norm of velocity gradients controls the possible break down of the strong solutions. Copyright © 2016 John Wiley & Sons, Ltd.
On a boundary value problem for a p‐Dirac equation
Authors: Al‐Yasiri Zainab R. , Gürlebeck Klaus
Published: February 2016

The p‐Laplace equation is a nonlinear generalization of the Laplace equation. This generalization is often used as a model problem for special types of nonlinearities. The p‐Laplace equation can be seen as a bridge between very general nonlinear equations and the linear Laplace equation. The aim of this paper is to solve the p‐Laplace equation for 1 < p < 2 and to find strong solutions. The idea is to apply a hypercomplex integral operator and spatial function theoretic methods to transform the p‐Laplace equation into the p‐Dirac equation. This equation will be solved iteratively by using a fixed‐point theorem. Applying operator‐theoretical methods for the p‐Dirac equation and p‐Laplace equation, the existence and uniqueness of solutions in certain Sobolev spaces will be proved. Copyright © 2016 John Wiley & Sons, Ltd.