bluuebunny/crossref_metadata_2025 huggingface dataset:
Host cell protein testing by ELISAs and the use of orthogonal methods
Authors: Zhu‐Shimoni Judith , Yu Christopher , Nishihara Julie , Wong Robert M. , Gunawan Feny , Lin Margaret , Krawitz Denise , Liu Peter , Sandoval Wendy , Vanderlaan Martin
Published: July 2014

Host cell proteins (HCPs) are among the process‐related impurities monitored during recombinant protein pharmaceutical process development. The challenges of HCP detection include (1) low levels of residual HCPs present in large excess of product protein, (2) the assay must measure a large number of different protein analytes, and (3) the population of HCP species may change during process development. Suitable methods for measuring process‐related impurities are needed to support process development, process validation, and control system testing. A multi‐analyte enzyme‐linked immunosorbent assay (ELISA) is the workhorse method for HCP testing due to its high throughput, sensitivity and selectivity. However, as the anti‐HCP antibodies, the critical reagents for HCP ELISA, do not comprehensively recognize all the HCP species, it is especially important to ensure that weak and non‐immunoreactive HCPs are not overlooked by the ELISA. In some cases limited amount of antibodies to HCP species or antigen excess causes dilution‐dependent non‐linearity with multi‐product HCP ELISA. In our experience, correct interpretation of assay data can lead to isolation and identification of co‐purifying HCP with the product in some cases. Moreover, even if the antibodies for a particular HCP are present in the reagent, the corresponding HCP may not be readily detected in the ELISA due to antibody/antigen binding conditions and availability of HCP epitopes. This report reviews the use of the HCP ELISA, discusses its limitations, and demonstrates the importance of orthogonal methods, including mass spectrometry, to complement the platform HCP ELISA for support of process development. In addition, risk and impact assessment for low‐level HCPs is also outlined, with consideration of clinical information. Biotechnol. Bioeng. 2014;111: 2367–2379. © 2014 Wiley Periodicals, Inc.
Age of second language acquisition affects nonverbal conflict processing in children: an fMRI study
Authors: Mohades Seyede Ghazal , Struys Esli , Van Schuerbeek Peter , Baeken Chris , Van De Craen Piet , Luypaert Robert
Published: July 2014

Background

In their daily communication, bilinguals switch between two languages, a process that involves the selection of a target language and minimization of interference from a nontarget language. Previous studies have uncovered the neural structure in bilinguals and the activation patterns associated with performing verbal conflict tasks. One question that remains, however is whether this extra verbal switching affects brain function during nonverbal conflict tasks.

Methods

In this study, we have used fMRI to investigate the impact of bilingualism in children performing two nonverbal tasks involving stimulus–stimulus and stimulus–response conflicts. Three groups of 8–11‐year‐old children – bilinguals from birth (2L1), second language learners (L2L), and a control group of monolinguals (1L1) – were scanned while performing a color Simon and a numerical Stroop task. Reaction times and accuracy were logged.

Results

Compared to monolingual controls, bilingual children showed higher behavioral congruency effect of these tasks, which is matched by the recruitment of brain regions that are generally used in general cognitive control, language processing or to solve language conflict situations in bilinguals (caudate nucleus, posterior cingulate gyrus, STG, precuneus). Further, the activation of these areas was found to be higher in 2L1 compared to L2L.

Conclusion

The coupling of longer reaction times to the recruitment of extra language‐related brain areas supports the hypothesis that when dealing with language conflicts the specialization of bilinguals hampers the way they can process with nonverbal conflicts, at least at early stages in life.
Mixed Methods Studies in Environmental Management Research: Prevalence, Purposes and Designs
Authors: Molina‐Azorín José F. , López‐Gamero María D.
Published: July 2014

Mixed methods research, that is, the combined use of quantitative and qualitative methods in the same study, is a popular approach in several fields. However, its use in the field of environmental management and sustainable development has not been examined. The authors review the application of mixed methods research in the journal Business Strategy and the Environment in the last ten years. A total of 340 articles have been read and reviewed, and 26 mixed methods studies have been identified. The main purposes and mixed methods designs are examined. Suggestions on why and how to use mixed methods research are offered, and recommendations are provided to guide future mixed methods studies to advance our understanding of environmental management topics. Copyright © 2014 John Wiley & Sons, Ltd and ERP Environment
Decentralized group key management for hierarchical access control using multilinear forms
Authors: Zhou Wei , Xu Yang , Wang Guojun
Published: July 2014

Key management becomes more difficult in multiprivileged group communications due to the dynamic membership and the complex relations between users and resources. Because centralized key management schemes have the drawbacks of the single point of failure, and performance bottleneck and distributed key management schemes are not scalable and lack of central control, decentralized key management schemes are proposed as a tradeoff between them. In this paper, we propose a decentralized group key management scheme using multilinear forms for dynamic multiprivileged groups. Once users join/leave the group and change their privileges, the related session keys should be updated. The rekeying in the joining operation is relatively simple because the keys are deduced from the previous keys based on a one‐way function. When rekeying for one leaving/switching operation, a uniform rekeying material is negotiated between the related service groups (SGs) by using multilinear forms. Compared with other schemes in which several rounds of negotiations are executed for rekeying in each joining/leaving/switching operation, only one round of negotiation is required in each leaving/switching operation of our decentralized group key management scheme. At last, the affected session keys can be deduced by the related SGs. Our proposed scheme also supports the dynamic formation and decomposition of SGs, which provides good scalability. Security analysis is provided to show that the proposed scheme is secure. The performance analysis and the simulation results show that the proposed scheme reduces the communication cost greatly. Copyright © 2014 John Wiley & Sons, Ltd.
Performance analyses of adaptive noncoherent receivers for MC‐CDMA communications
Authors: Chen Jun‐Da , Ueng Fang‐Biau , Shen Ye‐Shun , Cheng Yuan‐Hung
Published: July 2014

In this paper, we propose differential phase‐shift keying (DPSK) noncoherent receivers for multicarrier code division multiple access systems in multipath channels. The noncoherent receivers are composed of a linear equalizer and a decision‐feedback differential detector to detect DPSK signals. The performances of the proposed noncoherent receivers can be improved by increasing the number of feedback symbols. For an infinite number of feedback symbols, the optimum weight can be derived analytically, and the performances of the proposed noncoherent receivers approach that of the conventional coherent receiver. For adaptation of the equalizer coefficients, modified least mean square and recursive least squares algorithms are proposed. Furthermore, the reduced‐rank schemes are proposed to simplify the system complexities. Some simulation examples are given to show the system performances of the four proposed receivers. Copyright © 2014 John Wiley & Sons, Ltd.
Developmental trajectories of disordered eating from early adolescence to young adulthood: A longitudinal study
Authors: Slane Jennifer D. , Klump Kelly L. , McGue Matthew , Iacono William G.
Published: July 2014

Objective

Research examining changes in eating disorder symptoms across adolescence suggests an increase in disordered eating from early to late adolescence. However, relevant studies have largely been cross‐sectional in nature and most have not examined the changes in the attitudinal symptoms of eating disorders (e.g., weight concerns). This longitudinal study aimed to address gaps in the available data by examining the developmental trajectories of disordered eating in females from preadolescence into young adulthood.

Method

Participants were 745 same‐sex female twins from the Minnesota Twin Family Study. Disordered eating was assessed using the Total Score, Body Dissatisfaction subscale, Weight Preoccupation subscale, and a combined Binge Eating and Compensatory Behavior subscale from the Minnesota Eating Behavior Survey assessed at the ages of 11, 14, 18, 21, and 25. Several latent growth models were fit to the data to identify the trajectory that most accurately captures the changes in disordered eating symptoms from 11 to 25 years.

Results

The best‐fitting models for overall levels of disordered eating, body dissatisfaction, and weight preoccupation showed an increase in from 11 through 25 years. In contrast, bulimic behaviors increased to age of 18 and then stabilized to age of 25.

Discussion

The findings expanded upon extant research by investigating longitudinal, symptom specific, within‐person changes and showing an increase in cognitive symptoms into young adulthood and the stability of disordered eating behaviors past late adolescence. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:793–801)
(Dinitrogen)molybdenum Complexes Supported by Asymmetric Silicon‐Centered Tripod Ligands: Steric and Electronic Influences on the Coordination of Mono‐ and Diphosphine Coligands
Authors: Broda Henning , Krahmer Jan , Tuczek Felix
Published: July 2014

A reliable and generally applicable synthetic route for the rational synthesis of silicon‐centered tripod ligands with mixed dialkylphosphine/diarylphosphine donors is developed. On the basis of this protocol, two new asymmetric SiPPP′ ligands, SiPMe2PPh and SiPMe2PiPr, were prepared and employed for the synthesis of (dinitrogen)molybdenum complexes of the types [Mo(N2)(SiPPP′)(P2)] [P2 = (diphenylphosphino)methane (dppm), (dimethylphosphino)methane (dmpm), or two PMe2Ph] and [Mo(N2)2(SiPPP′)(PMe2Ph)]. The constitution of the complexes is elucidated by 31P NMR spectroscopy and analyzed on the basis of steric and electronic factors. The activation of N2 in the synthesized dinitrogen complexes is determined by IR spectroscopy and correlated with the donor/acceptor properties of the phosphine coligands.
Experimental and DFT/Time‐Dependent DFT Studies on Neutral and One‐Electron‐Reduced Quinoxaline and Pyrazine Precursors and Their Mononuclear (PdII, PtII) Derivatives
Authors: Donzello Maria Pia , De Mori Giorgia , Viola Elisa , Futur David , Fu Zhen , Rizzoli Corrado , Mannina Luisa , Bodo Enrico , Astolfi Maria Luisa , Ercolani Claudio , Kadish Karl M.
Published: July 2014

Electrochemical and UV/Vis spectral studies on the quinoxaline compound 2,3‐di(2‐pyridyl)‐6,7‐dicyano‐1,4‐quinoxaline, [(CN)2Py2Qx], its metallated derivatives [(CN)2Py2QxMCl2] (M = PdII, PtII) and their analogues sharing the dicyanopyrazine fragment are presented and discussed. X‐ray work on the new quinoxaline complex [(CN)2Py2QxPtCl2] establishes that PtII is coordinated to the pyridine N atoms (“py–py” coordination). The spectra of the 1– charged quinoxaline and pyrazine compounds show new intense absorptions in the region of 500–900 nm, and redshifted bands in the 250–400 nm region. By using DFT/time‐dependent DFT calculations, the spin density and spectral features of both couples of precursors and PtII derivatives were investigated in terms of single‐electron excitations between the Kohn–Sham orbitals of the optimized structures in the gas and condensed phases. A detailed comparison is allowed of the experimental and calculated spectral features of the neutral and 1– charged species.
Reductive Behavior of [Fe2(CO)4(κ2‐dmpe){μ‐(SCH2)2NBn}]: Effect of Symmetrization on the Rotated Conformation in FeI‐FeI Models of [2Fe]H Subsite of [Fe‐Fe]­H2ases
Authors: De Gioia Luca , Elleouet Catherine , Munery Sabrina , Pétillon François Y. , Schollhammer Philippe , Talarmin Jean , Zampella Giuseppe
Published: July 2014

The reduction of the compound [Fe2(CO)4(κ2‐dmpe){μ‐(SCH2)2NBn}] [dmpe = 1,2‐bis(dimethylphosphino)ethane], which is considered as an FeI‐FeI model of the [2Fe]H subsite of [Fe‐Fe]H2ases with a rotated conformation in the solid state, was investigated by cyclic voltammetry. Under reductive conditions, [Fe2(CO)4(κ2‐dmpe){μ‐(SCH2)2NBn}] undergoes electron‐transfer‐catalyzed isomerization to afford an isomer featuring a bridging diphosphine [Fe2(CO)4(μ‐dmpe){μ‐(SCH2)2NBn}]. Comparison of the crystallographic structures of the two isomers affords unique and direct experimental evidence that dissymmetrical coordination of the chelate ligand is required to promote the rotated conformation at one iron atom in this compound. DFT calculations were performed to rationalize this isomerization process and the slightly distorted structure of [Fe2(CO)4(μ‐dmpe){μ‐(SCH2)2NBn}]. The symmetrization of the coordination sphere results in the disruption of the agostic interaction that stabilized the rotated isomer.
Uniaxial Strain Effect of the Moderately Dimerized Molecular Conductor β‐(meso‐DMBEDT‐TTF)2PF6
Authors: Nishida Yohei , Isono Takayuki , Ueda Akira , Mori Hatsumi
Published: July 2014

The anisotropic band structure and electrical resistivity under uniaxial strain were investigated for the moderately dimerized molecular conductor β‐(meso‐DMBEDT‐TTF)2PF6 [DMBEDT‐TTF = dimethylbis(ethylenedithio)tetrathiafulvalene], which has an intermediate electronic state between 3/4‐filled and effective 1/2‐filled band structures at ambient pressure. The calculated energy overlap of the upper and lower bands increased more rapidly by applying uniaxial strain along the c axis than along the (a–b) axis towards the 3/4‐filled band structure, which is related to intersite electronic correlation, and the energy gap between these bands is estimated to be larger with application of uniaxial strain along the (a+b) axis towards an effective 1/2‐filled band structure, which is related to intrasite electronic correlation. The electrical resistivity under uniaxial strain along the c axis indicates the semiconducting behavior from 300 K and the superconducting (SC) transitions at 4.6–2.8 K under 0.10–0.41 GPa. On the other hand, the metal–insulator transition is not completely suppressed up to 0.8 GPa and SC transitions appear at 4.5–2.6 K under 0.16–0.45 GPa with uniaxial strain along the (a–b) axis. If this uniaxial strain results in semiconducting behavior and positive magnetoresistance related to intersite correlation, the SC states are observed under hydrostatic pressure, which indicates that the SC state is deeply related to the charge‐ordered state.
N‐Heterocyclic Carbene Catalysis as a Tool for Gaining Access to the 3,4‐Dihydropyran‐2‐one Skeleton
Authors: Albanese Domenico C. M. , Gaggero Nicoletta
Published: July 2014

An overview of the progress made in the synthesis of 3,4‐dihydropyran‐2‐ones since the development of NHC catalysis is reported. Two distinct classes of species – electrophilic α,β‐unsaturated acylazolium and nucleophilic azolium enol/enolate intermediates – can easily be produced from different substrates through the intermediacy of NHC catalysis. They enable the construction of the 3,4‐dihydropyran‐2‐one skeleton, the core of natural and synthetic products with significant biological activities, through Michael additions, cycloadditions and rearrangements.
Oxidative toxicity of perfluorinated chemicals in green mussel and bioaccumulation factor dependent quantitative structure–activity relationship
Authors: Liu Changhui , Chang Victor W.C. , Gin Karina Y.H.
Published: July 2014

Concerns regarding perfluorinated chemicals (PFCs) have risen in recent years because of their ubiquitous presence and high persistency. However, data on the environmental impacts of PFCs on marine organisms are very limited. Oxidative toxicity has been suggested to be one of the major toxic pathways for PFCs to induce adverse effects on organisms. To investigate PFC–induced oxidative stress and oxidative toxicity, a series of antioxidant enzyme activities and oxidative damage biomarkers were examined to assess the adverse effects of the following 4 commonly detected compounds: perfluoro-octanesulfonate, perfluoro-ocanoic acid, perfluorononanoic acid, and perfluorodecanoic acid, on green mussel (Perna viridis). Quantitative structure–activity relationship (QSAR) models were also established. The results showed that all the tested PFCs are able to induce antioxidant response and oxidative damage on green mussels in a dose-dependent manner. At low exposure levels (0 µg/L–100 µg/L), activation of antioxidant enzymes (catalase [CAT] and superoxide dismutase [SOD]) was observed, which is an adaptive response to the excessive reactive oxygen species induced by PFCs, while at high exposure levels (100 µg/L–10 000 µg/L), PFCs were found to inhibit some enzyme activity (glutathione S-transferase and SOD) where the organism's ability to respond in an adaptive manner was compromised. The oxidative stress under high PFC exposure concentration also led to lipid and DNA damage. PFC–induced oxidative toxicity was found to be correlated with the bioaccumulation potential of PFCs. Based on this relationship, QSAR models were established using the bioaccumulation factor (BAF) as the molecular descriptor for the first time. Compared with previous octanol–water partition coefficient–dependent QSAR models, the BAF-dependent QSAR model is more suitable for the impact assessment of PFCs and thus provides a more accurate description of the toxic behavior of these compounds. Environ Toxicol Chem 2014;33:2323–2332. © 2014 SETAC
Aqueous and lipid nuclear magnetic resonance metabolomic profiles of the earthworm Aporrectodea caliginosa show potential as an indicator species for environmental metabolomics
Authors: Brown Jeffrey N. , Samuelsson Linda , Bernardi Giuliana , Gooneratne Ravi , Larsson D.G. Joakim
Published: July 2014

The common pasture earthworm Aporrectodea caliginosa has often been neglected in environmental metabolomics in favor of species easily bred in the laboratory. The present study assigns aqueous metabolites in A. caliginosa using high-resolution 1- and 2-dimensional nuclear magnetic resonance (NMR) spectroscopy. In total, 51 aqueous metabolites were identified, including typical amino acids (alanine, leucine, asparagine, phenylalanine), sugars (maltose, glucose), the dominant earthworm-specific 2-hexyl-5-ethyl-furansulfonate, and several previously unreported metabolites (oxoglutarate, putrescine). Examining the lesser-known earthworm lipid metabolome showed various lipid fatty acyl chains, cholesterol, and phosphatidylcholine. To briefly test if the NMR metabolomic techniques could differentiate A. caliginosa from different sites, earthworms were collected from 2 adjacent farms. Orthogonal partial least squares discriminant analysis detected metabolomic differences, suggesting the worms from the 2 sites differed in their energy metabolism, as indicated by altered levels of alanine, glutamine, glutamate, malate, fumarate, and lipids. Evidence of greater utilization of lipid energy reserves and onset of protein catabolism was also present. While the precise cause of the metabolomic differences could not be determined, the results show the potential of this species for further environmental metabolomic studies. Environ Toxicol Chem 2014;33:2313–2322. © 2014 SETAC
An investigation of positive and inverted hemodynamic response functions across multiple visual areas
Authors: Puckett Alexander M. , Mathis Jedidiah R. , DeYoe Edgar A.
Published: July 2014

Recent studies have demonstrated significant regional variability in the hemodynamic response function (HRF), highlighting the difficulty of correctly interpreting functional MRI (fMRI) data without proper modeling of the HRF. The focus of this study was to investigate the HRF variability within visual cortex. The HRF was estimated for a number of cortical visual areas by deconvolution of fMRI blood oxygenation level dependent (BOLD) responses to brief, large‐field visual stimulation. Significant HRF variation was found across visual areas V1, V2, V3, V4, VO‐1,2, V3AB, IPS‐0,1,2,3, LO‐1,2, and TO‐1,2. Additionally, a subpopulation of voxels was identified that exhibited an impulse response waveform that was similar, but not identical, to an inverted version of the commonly described and modeled positive HRF. These voxels were found within the retinotopic confines of the stimulus and were intermixed with those showing positive responses. The spatial distribution and variability of these HRFs suggest a vascular origin for the inverted waveforms. We suggest that the polarity of the HRF is a separate factor that is independent of the suppressive or activating nature of the underlying neuronal activity. Correctly modeling the polarity of the HRF allows one to recover an estimate of the underlying neuronal activity rather than discard the responses from these voxels on the assumption that they are artifactual. We demonstrate this approach on phase‐encoded retinotopic mapping data as an example of the benefits of accurately modeling the HRF during the analysis of fMRI data. Hum Brain Mapp 35:5550–5564, 2014. © 2014 Wiley Periodicals, Inc.
An ALE meta‐analysis on the audiovisual integration of speech signals
Authors: Erickson Laura C. , Heeg Elizabeth , Rauschecker Josef P. , Turkeltaub Peter E.
Published: July 2014

The brain improves speech processing through the integration of audiovisual (AV) signals. Situations involving AV speech integration may be crudely dichotomized into those where auditory and visual inputs contain (1) equivalent, complementary signals (validating AV speech) or (2) inconsistent, different signals (conflicting AV speech). This simple framework may allow the systematic examination of broad commonalities and differences between AV neural processes engaged by various experimental paradigms frequently used to study AV speech integration. We conducted an activation likelihood estimation metaanalysis of 22 functional imaging studies comprising 33 experiments, 311 subjects, and 347 foci examining “conflicting” versus “validating” AV speech. Experimental paradigms included content congruency, timing synchrony, and perceptual measures, such as the McGurk effect or synchrony judgments, across AV speech stimulus types (sublexical to sentence). Colocalization of conflicting AV speech experiments revealed consistency across at least two contrast types (e.g., synchrony and congruency) in a network of dorsal stream regions in the frontal, parietal, and temporal lobes. There was consistency across all contrast types (synchrony, congruency, and percept) in the bilateral posterior superior/middle temporal cortex. Although fewer studies were available, validating AV speech experiments were localized to other regions, such as ventral stream visual areas in the occipital and inferior temporal cortex. These results suggest that while equivalent, complementary AV speech signals may evoke activity in regions related to the corroboration of sensory input, conflicting AV speech signals recruit widespread dorsal stream areas likely involved in the resolution of conflicting sensory signals. Hum Brain Mapp 35:5587–5605, 2014. © 2014 Wiley Periodicals, Inc.
Outcomes of nodal metastatic cutaneous squamous cell carcinoma of the head and neck treated in a regional center
Authors: Schmidt Campbell , Martin Jarad M. , Khoo Eric , Plank Ashley , Grigg Roger
Published: July 2014

Background

Given its metastatic potential and high incidence, cutaneous squamous cell carcinoma of the head and neck (SCCHN) has significant morbidity and mortality.

Methods

We conducted a retrospective review of prospectively collected data for 113 consecutive patients with nodal metastatic cutaneous SCCHN treated surgically with curative intent in a regional center. Survival curves were generated by the Kaplan–Meier method.

Results

Five‐year overall survival (OS), disease‐specific survival (DSS), and disease‐free survival (DFS) were 80%, 83%, and 75%, respectively. Twenty‐six patients (23%) relapsed, with 92% of relapses occurring within 2 years of surgery. Immunosuppression (p = .008) and N classification (p = .043) predicted decreased DFS on univariate analysis. On multivariate analysis, only immunosuppression independently predicted DFS (p = .034).

Conclusion

This study validates the current N classification system, supports the adverse effect of immunosuppression, and suggests that intense follow‐up for 2 years postsurgery is warranted. Survival at this regional center is comparable to that achieved at metropolitan tertiary cancer centers. © 2015 Wiley Periodicals, Inc. Head Neck 37: 1808–1815, 2015
Excess mortality on the liver transplant waiting list: Unintended policy consequences and model for End‐Stage Liver Disease (MELD) inflation
Authors: Northup Patrick Grant , Intagliata Nicolas Michael , Shah Neeral Lalit , Pelletier Shawn Joseph , Berg Carl Lansing , Argo Curtis Kent
Published: July 2014

The Model for End‐Stage Liver Disease (MELD) allocation system for liver transplantation provides “exceptions” for diseases such as hepatocellular carcinoma (HCC). It was the aim of this study to assess equipoise between exception candidates and nonexception candidates on the waiting list and to assess if the exception system contributes to steadily increasing regional MELD at transplant. In all, 78,595 adult liver transplant candidates between January 2005 and December 2012 were analyzed. Yearly trends in waiting list characteristics and transplantation rates were analyzed for statistical association with MELD exceptions. Regional variations in these associations and the effect of exceptions on regional MELD scores at transplant were also analyzed. 27.29% of the waiting list was occupied by candidates with exceptions. Candidates with exceptions fared much better on the waiting list compared to those without exceptions in mean days waiting (HCC 237 versus non‐HCC 426), transplantation rates (HCC 79.05% versus non‐HCC 40.60%), and waiting list death rates (HCC 4.49% versus non‐HCC 24.63%). Strong regional variation in exception use occurred but exceptions were highly correlated with waiting list death rates, transplantation rates, and MELD score at removal in all regions. In a multivariate model predicting MELD score at transplant within regions, the percentage of HCC MELD exceptions was the strongest independent predictor of regional MELD score at transplant. Conclusion: Liver transplant candidates with MELD exceptions have superior outcomes compared to nonexception candidates and the current MELD exception system is largely responsible for steadily increasing MELD scores at transplant independent of geography. (Hepatology 2015;61:285–291)
Antagonistic interaction between Wnt and Notch activity modulates the regenerative capacity of a zebrafish fibrotic liver model
Authors: Huang Mianbo , Chang Angela , Choi Minna , Zhou David , Anania Frank A. , Shin Chong Hyun
Published: July 2014

In chronic liver failure patients with sustained fibrosis, excessive accumulation of extracellular matrix proteins substantially dampens the regenerative capacity of the hepatocytes, resulting in poor prognosis and high mortality. Currently, the mechanisms and the strategies of inducing endogenous cellular sources such as hepatic progenitor cells (HPCs) to regenerate hepatocytes in various contexts of fibrogenic stimuli remain elusive. Here we aim to understand the molecular and cellular mechanisms that mediate the effects of sustained fibrosis on hepatocyte regeneration using the zebrafish as a model. In the ethanol-induced fibrotic zebrafish model, we identified a subset of HPCs, responsive to Notch signaling, that retains its capacity to regenerate as hepatocytes. Discrete levels of Notch signaling modulate distinct cellular outcomes of these Notch-responsive HPCs in hepatocyte regeneration. Lower levels of Notch signaling promote amplification and subsequent differentiation of these cells into hepatocytes, while high levels of Notch signaling suppress these processes. To identify small molecules facilitating hepatocyte regeneration in the fibrotic liver, we performed chemical screens and identified a number of Wnt agonists and Notch antagonists. Further analyses demonstrated that these Wnt agonists are capable of attenuating Notch signaling by inducing Numb, a membrane-associated protein that inhibits Notch signaling. This suggests that the antagonistic interplay between Wnt and Notch signaling crucially affects hepatocyte regeneration in the fibrotic liver.

Conclusion

: Our findings not only elucidate how signaling pathways and cell-cell communications direct the cellular response of HPCs to fibrogenic stimuli, but also identify novel potential therapeutic strategies for chronic liver disease. (Hepatology 2014;60:1753–1766)
Theoretical study on the gas phase reaction of propargyl alcohol with hydroxyl radical
Authors: Zhang Yunju , Sun Jingyu , Zhang Wanqiao , Tang Yizhen , Wang Rongshun
Published: July 2014

The reaction of propargyl alcohol with hydroxyl radical has been studied extensively at CCSD(T)/aug‐cc‐pVTZ//MP2/cc‐pVTZ level. This is the first time to gain a conclusive insight into the reaction mechanism and kinetics for this important reaction in detail. Two reaction mechanisms were revealed, namely addition/elimination and hydrogen abstraction mechanism. The reaction mechanism confirms that OH addition to CC triple bond forms the chemically activated adducts, IM1 (·CHCOHCH2OH) and IM2 (CHOH·CCH2OH), and the hydrogen abstraction pathways (CH2OH bonded to the carbon atom and alcohol hydrogen) may occur via low barriers. Harmonic model of Rice–Ramsperger–Kassel–Marcus theory and variational transition state theory are used to calculate the overall and individual rate constants over a wide range of temperatures and pressures. The calculated rate constants are in good agreement with the experimental data. At atmospheric pressure with Ar as bath gas, IM1 (·CHCOHCH2OH) and IM2 (CHOH·CCH2OH) formed by collisional stabilization are dominant in the low temperature range. The production of CHCCHOH + H2O via hydrogen abstraction becomes dominate at higher temperature. The fraction of IM3 (CH2COHCH2·O) is very significant over the moderate temperature range. © 2014 Wiley Periodicals, Inc.
Brain infection with Staphylococcus aureus leads to high extracellular levels of glutamate, aspartate, γ‐aminobutyric acid, and zinc
Authors: Hassel Bjørnar , Dahlberg Daniel , Mariussen Espen , Goverud Ingeborg Løstegaard , Antal Ellen‐Ann , Tønjum Tone , Mæhlen Jan
Published: July 2014

Staphylococcal brain infections may cause mental deterioration and epileptic seizures, suggesting interference with normal neurotransmission in the brain. We injected Staphylococcus aureus into rat striatum and found an initial 76% reduction in the extracellular level of glutamate as detected by microdialysis at 2 hr after staphylococcal infection. At 8 hr after staphylococcal infection, however, the extracellular level of glutamate had increased 12‐fold, and at 20 hr it had increased >30‐fold. The extracellular level of aspartate and γ‐aminobutyric acid (GABA) also increased greatly. Extracellular Zn2+, which was estimated at ∼2.6 µmol/liter in the control situation, was increased by 330% 1–2.5 hr after staphylococcal infection and by 100% at 8 and 20 hr. The increase in extracellular glutamate, aspartate, and GABA appeared to reflect the degree of tissue damage. The area of tissue damage greatly exceeded the area of staphylococcal infiltration, pointing to soluble factors being responsible for cell death. However, the N‐methyl‐D‐aspartate receptor antagonist MK‐801 ameliorated neither tissue damage nor the increase in extracellular neuroactive amino acids, suggesting the presence of neurotoxic factors other than glutamate and aspartate. In vitro staphylococci incubated with glutamine and glucose formed glutamate, so bacteria could be an additional source of infection‐related glutamate. We conclude that the dramatic increase in the extracellular concentration of neuroactive amino acids and zinc could interfere with neurotransmission in the surrounding brain tissue, contributing to mental deterioration and a predisposition to epileptic seizures, which are often seen in brain abscess patients.© 2014 Wiley Periodicals, Inc.
Spectroscopic characterisation of crusts interstratified with prehistoric paintings preserved in open‐air rock art shelters
Authors: Hernanz Antonio , Ruiz‐López Juan F. , Madariaga Juan Manuel , Gavrilenko Egor , Maguregui Maite , Fdez‐Ortiz de Vallejuelo Silvia , Martínez‐Arkarazo Irantzu , Alloza‐Izquierdo Ramiro , Baldellou‐Martínez Vicente , Viñas‐Vallverdú Ramón , Rubio i Mora Albert , Pitarch Àfrica , Giakoumaki Anastasia
Published: July 2014

In situ micro‐Raman spectroscopy (μ‐RS) of rock art paintings in open‐air rock shelters entails several difficulties: sunlight, wind, dust and crusts that mask Raman signals from the pigments and any other component of the paint recipe. These problems have been considered in the present work. Special attention has been devoted to the presence of crusts. Five rock art sites in the eastern Iberian Peninsula with outstanding difficulties to be analysed by this technique have been the object of this study. In situ energy dispersive X‐ray fluorescence and diffuse reflectance infrared Fourier transform spectroscopy using portable instruments have provided important help. Moreover, microstratigraphic studies by μ‐RS and scanning electronic microscopy combined with energy dispersive X‐ray spectroscopy of micro‐specimens from the painting panels have revealed the distribution of the different components. Dolomite and calcite are dominant minerals in the rock substrata. Whewellite, gypsum, calcite, clay, dolomite, α‐quartz, anatase and haematite have been found on the surface of the painting panels or forming stratified layers in the crusts. Haematite and amorphous carbon have been detected in red and black pictographs, respectively. Copyright © 2014 John Wiley & Sons, Ltd.
Computational complexity of finding Pareto efficient outcomes for biobjective lot‐sizing models
Authors: Romeijn H. Edwin , Morales Dolores Romero , Van den Heuvel Wilco
Published: July 2014

In this article, we study a biobjective economic lot‐sizing problem with applications, among others, in green logistics. The first objective aims to minimize the total lot‐sizing costs including production and inventory holding costs, whereas the second one minimizes the maximum production and inventory block expenditure. We derive (almost) tight complexity results for the Pareto efficient outcome problem under nonspeculative lot‐sizing costs. First, we identify nontrivial problem classes for which this problem is polynomially solvable. Second, if we relax any of the parameter assumptions, we show that (except for one case) finding a single Pareto efficient outcome is an ‐hard task in general. Finally, we shed some light on the task of describing the Pareto frontier. © 2014 Wiley Periodicals, Inc. Naval Research Logistics 61: 386–402, 2014
Unified analysis of preconditioning methods for saddle point matrices
Authors: Axelsson Owe
Published: July 2014

Short and unified proofs of spectral properties of major preconditioners for saddle point problems are presented. The need to sufficiently accurately construct approximations of the pivot block and Schur complement matrices to obtain real eigenvalues or eigenvalues with positive real parts and non‐dominating imaginary parts are pointed out. The use of augmented Lagrangian methods for more ill‐conditioned problems are discussed. Copyright © 2014 John Wiley & Sons, Ltd.
Thrombosis of torcular herophili: diagnosis, prenatal management, and outcome
Authors: Rayssiguier Romy , Dumont Coralie , Flunker Sabrina , Couture Alain , Boulot Pierre , Prodhomme Olivier
Published: July 2014

Objectives

The objective of this article is to describe and assess prenatal imaging findings, fetal and postnatal outcomes of thrombosis of torcular herophili, and to determine diagnostic features, pathophysiology, prognosis, and optimal management.

Methods

Over a decade, we compiled the largest single‐center retrospective study of outcomes. Fetal magnetic resonance imaging (MRI) was used to confirm the sonographic suspicion and monitor thrombosis of torcular herophili. We noted prenatal and postnatal imaging specifications, pregnancy outcomes, and clinical and radiological pediatric monitoring. Analysis of findings and review of the literature allowed us to define prognostic factors.

Results

In eight cases of prenatal diagnosis of thrombosis of torcular herophili, MRI outcomes were specific. There were five deliveries at full term, two terminations of pregnancy, and one fetal demise in utero. Neonates had a good clinical and radiological outcome. Factors of poor prognosis were deep venous sinus thrombosis, enduring mass effect, brain parenchymal injury, and heart failure related to dural arteriovenous shunt.

Conclusion

Among dural sinus malformations, thrombosis of torcular herophili with or without extension at the posterior segment of the longitudinal sinus frequently has a good prognosis. It is urgent to wait because the prognosis can only be ascertained over time by means of ultrasound scan and MRI monitoring. © 2014 John Wiley & Sons, Ltd.
Sonographic diagnosis of ectopia cordis before 9 weeks of gestation
Authors: Sepulveda Waldo , Andreeva Elena , Machado Luiz E.
Published: July 2014

What's already known about this topic?

Ectopia cordis is a rare, almost invariably lethal, condition that can be readily diagnosed by prenatal sonography.

The prenatal diagnosis of ectopia cordis before 9 weeks has not been reported.

What does this study add?

This series of three cases documents, the earliest diagnosis of ectopia cordis reported to date.

Ectopia cordis seems to be associated with a high lethality rate in early embryos, suggesting that this condition could be more frequent than previously reported.
Hydrophobically modified polyelectrolyte for improved oxygen barrier in nanobrick wall multilayer thin films
Authors: Stevens Bart E. , Odenborg Patrick K. , Priolo Morgan A. , Grunlan Jaime C.
Published: July 2014

The influence of attaching hydrophobic side groups to a polyelectrolyte, used for deposition of a multilayer oxygen gas barrier thin film, was investigated. Polyethyleneimine (PEI) was labeled with pyrene and deposited in “quadlayers” of PEI, poly(acrylic acid), PEI, and sodium montmorillonite clay using layer‐by‐layer assembly. Thin films made of three repeating quadlayers using unmodified PEI had much lower density (1.24 g/cm3) than pyrene‐labeled PEI‐based films (1.45 g/cm3), which is believed to be the result of greater chain coiling from the increased hydrophobicity of pendant pyrene groups. This increased density in pyrene‐labeled PEI layers allowed three quadlayers to match the oxygen transmission rate of a four quadlayer film made with unmodified PEI. This discovery provides an additional tool for tailoring the barrier behavior of clay‐based multilayer thin films that could prove useful for a variety of packaging applications. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014, 52, 1153–1156
Noncommutative quantum field theory
Authors: Grosse H. , Wulkenhaar R.
Published: July 2014

We summarize our recent construction of the ϕ4‐model on four‐dimensional Moyal space. This is achieved by solving the quartic matrix model for a general external matrix in terms of the solution of a non‐linear equation for the 2‐point function and the eigenvalues of that matrix. The β‐function vanishes identically. For the Moyal model, the theory of Carleman type singular integral equations reduces the construction to a fixed point problem. The resulting Schwinger functions in position space are symmetric and invariant under the full Euclidean group. The Schwinger 2‐point function is reflection positive iff the diagonal matrix 2‐point function is a Stieltjes function.
Complex geometry of quantum cones
Authors: Brzeziński T.
Published: July 2014

The algebras obtained as fixed points of the action of the cyclic group ℤN on the coordinate algebra of the quantum disc are studied. These can be understood as coordinate algebras of quantum or non‐commutative cones. The following observations are made. First, contrary to the classical situation, the actions of ℤN are free and the resulting algebras are homologically smooth. Second, the quantum cone algebras admit differential calculi that have all the characteristics of calculi on smooth complex curves. Third, the corresponding volume forms are exact, indicating that the constructed algebras describe manifolds with boundaries.
Regulation of prostaglandin EP1 and EP4 receptor signaling by carrier‐mediated ligand reuptake
Authors: Chi Yuling , Suadicani Sylvia O. , Schuster Victor L.
Published: July 2014

After synthesis and release from cells, prostaglandin E2 (PGE2) undergoes reuptake by the prostaglandin transporter (PGT), followed by cytoplasmic oxidation. Although genetic inactivation of PGT in mice and humans results in distinctive phenotypes, and although experiments in localized environments show that manipulating PGT alters downstream cellular events, a direct mechanistic link between PGT activity and PGE2 (EP) receptor activation has not been made. Toward this end, we created two reconstituted systems to examine the effect of PGT expression on PGE2 signaling via two of its receptors (EP1 and EP4). In human embryonic kidney cells engineered to express the EP1 receptor, exogenous PGE2 induced a dose‐dependent increase in cytoplasmic Ca2+. When PGT was expressed at the plasma membrane, the PGE2 dose–response curve was right‐shifted, consistent with reduction in cell surface PGE2 availability; a potent PGT inhibitor acutely reversed this shift. When bradykinin was used to induce endogenous PGE2 release, PGT expression similarly induced a reduction in Ca2+ responses. In separate experiments using Madin–Darby Canine Kidney cells engineered to express the PGE2 receptor EP4, bradykinin again induced autocrine PGE2 signaling, as judged by an abrupt increase in intracellular cAMP. As in the EP1 experiments, expression of PGT at the plasma membrane caused a reduction in bradykinin‐induced cAMP accumulation. Pharmacological concentrations of exogenous PGE2 induced EP4 receptor desensitization, an effect that was mitigated by PGT. Thus, at an autocrine/paracrine level, plasma membrane PGT regulates PGE2 signaling by decreasing ligand availability at cell surface receptors.
Impact of DDT on FPSO explosion risk assessment
Authors: Hansen Olav Roald , Martini Remi , Choi Jaewoong , Ryu Yonghee
Published: July 2014

In recent explosion accidents on onshore petrochemical facilities, it has been concluded that a deflagration‐to‐detonation‐transition (DDT) took place, both with Liquefied Petroleum Gas (LPG) and gasoline vapor. DDT has also been observed in a number of large‐scale experiments. DDT leads to very high pressures (16–20 barg) and flame speeds (1,600–2,000 m/s) even outside congested regions and has a significant impact on the severity of the near‐field and far‐field explosion loads. It has not been generally accepted that DDT may be a threat at offshore petrochemical facilities and prediction tools have not been available. Thus, the potential effect of DDT is seldom considered. For Floating production, storage and offloading vessels (FPSOs), and even more Floating liquified natural gas vessels (FLNGs), due to larger dimensions and inventories, operators should be concerned that major explosion scenarios can lead to DDT phenomena.

Recently, a DDT prediction parameter was implemented in the Computational Fluid Dynamics (CFD) model FLACS, and with model adjustments it is possible to calculate DDT and effect on explosion loads with good precision. A CFD‐based FPSO explosion study is presented evaluating DDT potential and impact. DDT will mainly be a concern for large cloud sizes, often larger than commonly considered for design accidental loads for an FPSO (10−4/year). Mitigation by separation walls is also evaluated. © 2014 American Institute of Chemical Engineers Process Saf Prog 34: 44–57, 2015
PoliCon: a policy conciliation framework for heterogeneous mobile ad hoc networks
Authors: Maity Soumya , Ghosh Soumya K. , Al‐Shaer Ehab
Published: July 2014

It is increasingly important to implement a conflict‐free access control policies for co‐allied networks where different organizations are involve for a common goal. Mobile ad hoc networks are widely used for mission critical situations where teams from different organizational networks cooperate to form a single network to implement their respective operations. These teams (or quads) have different sets of local policies enforced for their own security resulting heterogeneity in access control. Each team wants to preserve its access control policies at a maximum level. Moreover, a set of allied policies govern the cooperation and interaction between the different teams, which may conflict with their local policies. The policy conflicts arise from the transitivity of policy rules, mobility of the nodes, cooperative behaviors, and so on. In addition, the policy rules may be temporal or static. To achieve the successful completion of the mission, it may be required to compromise with the stringency of the enforcement of the conflicting rules for the quads. In this paper, we propose an automated and formal framework to find the optimal conciliation of the policy rules to preserve the mission and thus ensure minimal compromise with the enforcement of policy for each quad. The efficacy of the work lies on optimizing the enforcement of access control policies to achieve the coalition instead of negating the policy. Copyright © 2014 John Wiley & Sons, Ltd.
Prospect of increasing secondary ion yields in ToF‐SIMS using water cluster primary ion beams
Authors: Sheraz (née Rabbani) S. , Barber A. , Berrueta Razo I. , Fletcher J. S. , Lockyer N.P. , Vickerman J. C.
Published: July 2014

Low ionization yields in time of flight secondary ion mass spectrometry (ToF‐SIMS) particularly from single cells and tissues are proving to be a significant limitation in allowing this technique to reach its full potential. A number of approaches including embedding the sample in water or spraying water above sample surface has shown great prospective for increasing the ionization yield by a factor of 10 to 100 through ‘proton mediated’ reaction. Based on this hypothesis, a water cluster primary ion source has been developed in collaboration with Ionoptika Ltd to generate giant water cluster ions (H2O)n+ (n = 1−10 000) using a similar supersonic jet expansion methodology as for argon cluster beams. The ion yields of arginine, cholesterol, angiotensin II and a lipid mix have been measured under static and high ion dose conditions using (H2O)5000+, (H2O)3000+, Ar3000+ and C60+ primary ion beams at 20 keV. An enhancement in yields up to a factor of around 4 is observed under water cluster impact, in comparison with C60+ at 1 × 1011 ions/cm2 ion dose, whereas this increases by around 10–50 times at high ion dose conditions. Copyright © 2014 John Wiley & Sons, Ltd.
Si− useful yields measured in Si, SiC, Si3N4 and SiO2: comparison between the Storing Matter technique and SIMS
Authors: Kasel B. , Wirtz T.
Published: July 2014

The storing matter technique was developed to tackle quantification issues encountered in SIMS due to matrix effects. Here, we demonstrate the quantitative capabilities of the technique by comparing the useful yield for Si− in different matrices exhibiting matrix effects in conventional SIMS analysis. Additionally, the effect of the collector material (Ag, Au, Cu and Ta) on the storing matter useful yield is investigated. Copyright © 2014 John Wiley & Sons, Ltd.