bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Briarenolides H and I: New 8‐Hydroxybriarane Diterpenoids from a Formosan Octocoral Briareum sp. (Briareidae).
Authors: Su Yin‐Du , Hwang Tsong‐Long , Lin Nai‐Cheng , Chen Yung‐Husan , Wu Yang‐Chang , Sheu Jyh‐Horng , Sung Ping‐Jyun
Published: January 2013

Two new 8‐hydroxybriarane diterpenoids, briarenolide H (I) and I (II), are isolated.
ChemInform Abstract: Catalytic Asymmetric Mannich Reaction of Glycine Schiff Bases with α‐Amido Sulfones as Precursors of Aliphatic Imines.
Authors: Hernando Elier , Gomez Arrayas Ramon , Carretero Juan C.
Published: January 2013

A general Cu(I)‐FeSulphos‐catalyzed Mannich reaction of glycinate Schiff bases (II) with imines generated in situ from α‐amido sulfones (I) and (IV) is described.
ChemInform Abstract: (‐)‐(S)‐Nakinadine B: First Asymmetric Synthesis.
Authors: Davies Stephen G. , Lee James A. , Roberts Paul M. , Shah Rushabh S. , Thomson James E.
Published: January 2013

The title compound (IV) is prepared in 9 steps and 17% overall yield from commercially available atropic acid.
ChemInform Abstract: Discovery of Triazolopyrimidine‐Based PDE8B Inhibitors: Exceptionally Ligand‐Efficient and Lipophilic Ligand‐Efficient Compounds for the Treatment of Diabetes.
Authors: DeNinno Michael P. , et al. et al.
Published: January 2013

A high throughput screening hit is deconstructed to optimize for ligand efficiency against PDE8B.
ChemInform Abstract: Unified Platform for the Chemical Reactivity and Catalytic Potential of Catalyst Nanoparticles of Even Very Diverse Structures and Characteristics for Nanotube (Including Carbon Nanotube) Syntheses
Authors: Mohammad S. Noor
Published: January 2013

Review: 150 refs.
ChemInform Abstract: Photofunctional Triplet Excited States of Cyclometalated Ir(III) Complexes: Beyond Electroluminescence
Authors: You Youngmin , Nam Wonwoo
Published: January 2013

Review: 287 refs.
ChemInform Abstract: From Nanographene and Graphene Nanoribbons to Graphene Sheets: Chemical Synthesis
Authors: Chen Long , Hernandez Yenny , Feng Xinliang , Muellen Klaus
Published: January 2013

Review: 93 refs.
ChemInform Abstract: Living Radical Polymerization by the RAFT Process — A Third Update
Authors: Moad Graeme , Rizzardo Ezio , Thang San H.
Published: January 2013

Review: 721 refs.
ChemInform Abstract: Coordination‐Like Chemistry of Phosphinidenes by Phosphanes
Authors: Protasiewicz John D.
Published: January 2013

Review: 78 refs.
ChemInform Abstract: General Consideration on Sialic Acid Chemistry
Authors: Cao Hongzhi , Chen Xi
Published: January 2013

Review: 120 refs.
ChemInform Abstract: Bioactive Natural Products from Papua New Guinea Marine Sponges
Authors: Noro Jeffrey C. , Kalaitzis John A. , Neilan Brett A.
Published: January 2013

Review: 132 refs.
ChemInform Abstract: Some Approaches for High Performance Polymer Based Membranes for Gas Separation: Block Copolymers, Carbon Molecular Sieves and Mixed Matrix Membranes
Authors: Buonomenna M. G. , Yave W. , Golemme G.
Published: January 2013

Review: 254 refs.
ChemInform Abstract: High‐Resolution Magic Angle Spinning‐Enabling Applications of NMR Spectroscopy to Semi‐Solid Phases
Authors: Power William P.
Published: January 2013

Review: 343 refs.
ChemInform Abstract: Recent Developments in Heteronuclear Multiple‐Bond Correlation Experiments
Authors: Schoefberger Wolfgang , Schlagnitweit Judith , Mueller Norbert
Published: January 2013

Review: 162 refs.
Zeolithe selbst gemacht!
Authors: Nick Sabine , Chomicz Zuzanna
Published: January 2013

Der Beitrag diskutiert am Beispiel der Zeolithe die Thematisierung moderner Materialien in der Schule. Nach einem Überblick über den strukturellen Aufbau und die strukturellen Baueinheiten von Zeolithe, werden die Synthesen zweier Zeolithe vorgestellt, welche ausgehend von einfachen Grundchemikalien und ohne großen apparativen Aufwand in einer solvothermal‐ähnlichen Reaktionsführung gelingen. Weiterhin werden Hinweise zur Analytik der Produkte gegeben und mögliche Folgeexperimente beschrieben.
Bildung für eine nachhaltige Entwicklung (BnE) in der Chemielehrerbildung
Authors: Burmeister Mareike , Eilks Ingo
Published: January 2013

Dieser Aufsatz beschreibt die Entwicklung eines Teilmoduls über Bildung für eine nachhaltige Entwicklung (BnE) für die universitäre Ausbildung von Chemielehrkräften. Das Teilmodul wurde durch Partizipative Aktionsforschung, ausgehend von theoretischen Konzepten der BnE und empirischen Untersuchungen zum Kenntnisstand von Lehramtsstudierenden und Referendaren, gestaltet und zyklisch entwickelt. Dieser Aufsatz diskutiert diese Entwicklung, stellt die Struktur des Teilmoduls vor und berichtet über Erfahrungen bei der Umsetzung.

This paper presents the development of a university chemistry teacher education module on Education for Sustainable Development (ESD). The module was cyclically developed and refined by Participatory Action Research on the base of a theoretical analysis of the literature and empirical investigation on the existing knowledge base of student teachers and teacher trainees. The paper discusses the process of development, presents the structure of the module, and reports experiences from its implementation.
Ester als Duftstoffe, rein synthetisch aus dem Labor
Authors: Aydemir Ibrahim , Firneis Christian , Trauschke Mathias
Published: January 2013

Im Rahmen eines Seminarfaches an einem niedersächsischen Gymnasium wurde das Thema „Ester als Duftstoffe“ durch eine Schülergruppe bearbeitet. Ihr Ziel war es, hochreine Ester unter Schulbedingungen herzustellen, um sie dann durch einen sensorischen Test durch Mitschüler überprüfen zu lassen. Der folgende Beitrag ist eine Gemeinschaftsarbeit von Schülern und dem betreuenden Lehrer.
Theoretical Study on the Rectifying Performance of Organoimido Derivatives of Hexamolybdates
Authors: Wen Shizheng , Yang Guochun , Yan Likai , Li Haibin , Su Zhongmin
Published: January 2013

We design a new type of molecular diode, based on the organoimido derivatives of hexamolybdates, by exploring the rectifying performances using density functional theory combined with the non‐equilibrium Green’s function. Asymmetric current–voltage characteristics were obtained for the models with an unexpected large rectification ratio. The rectifying behavior can be understood by the asymmetrical shift of the transmission peak observed under different polarities. It is interesting to find that the preferred electron‐transport direction in our studied system is different from that of the organic D‐bridge‐A system. The results show that the studied organic–inorganic hybrid systems have an intrinsically robust rectifying ratio, which should be taken into consideration in the design of the molecular diodes.
FPGA‐based embedded platform for fiber optic gyroscope signal denoising
Authors: Peesapati Rangababu , Sabat Samrat L. , K. P. Karthik , M. Narasimhappa , N. Giribabu , Nayak J.
Published: January 2013

This paper presents System on Chip (SoC) implementation of a proposed denoising algorithm for fiber optic gyroscope (FOG) signal. The SoC is developed using an Auxillary Processing Unit of the proposed algorithm and implemented in the Xilinx Virtex‐5‐FXT‐1136 field programmable gate array. SoC implementation of this application is first of its kind. The proposed algorithm namely adaptive moving average‐based dual‐mode Kalman filter (AMADMKF) is a hybrid of adaptive moving average and Kalman filter (KF) technique. The performance of the proposed AMADMKF algorithm is compared with the discrete wavelet transform and KF of different gains. Allan variance analysis, standard deviation and signal to noise ratio (SNR) are used to measure the efficiency of the algorithm. The experimental result shows that AMADMKF algorithm reduces the standard deviation or drift of the signal by an order of 100 and improves the SNR approximately by 80 dB. The Allan variance analysis result shows that this algorithm also reduces different types of random errors of the signal significantly. The proposed algorithm is found to be the best suited algorithm for denoising the FOG signal in both the static and dynamic environments. Copyright © 2013 John Wiley & Sons, Ltd.
A low‐power, area‐efficient multichannel receiver for micro MRI
Authors: Dehkhoda Fahimeh , Frounchi Javad , Al‐Sarawi Said
Published: January 2013

A new integrated, low‐noise, low‐power, and area‐efficient multichannel receiver for magnetic resonance imaging (MRI) is described. The proposed receiver presents an alternative technique to overcome the use of multiple receiver front‐ends in parallel MRI. The receiver consists of three main stages: low‐noise pre‐amplifier, quadrature down‐converter, and a band pass filter (BPF). These components are used to receive the nuclear magnetic resonance signals from a 3 × 3 array of micro coils. These signals are combined using frequency domain multiplexing (FDM) method in the pre‐amplifier and BPF stages, then amplified and filtered to remove any out‐of‐band noise before providing it to an analog‐to‐digital converter at the low intermediate frequency stage. The receiver is designed using a 90 nm CMOS technology to operate at the main B0 magnetic field of 9.4 T, which corresponds to 400 MHz. The receiver has an input referred noise voltage of 1.1 nV/√Hz, a total voltage gain of 87 dB, a power consumption of 69 mA from a 1 V supply voltage, and an area of 305 µm × 530 µm including the reference current and bias voltage circuits. Copyright © 2013 John Wiley & Sons, Ltd.
Inter‐ELM Ion Transport in the ASDEX Upgrade Far Scrape‐Off Layer
Authors: Kočan M. , Allan S. Y , Carpentier‐Chouchana S. , de Marné P. , Elmore S. , P. Gunn J. , Herrmann A. , Kirk A. , Kubič M. , Lunt T. , W. Müller H. , Pitts R. A. , Rohde V. , the ASDEX Upgrade Team
Published: January 2013

New measurements of ion transport in the scrape‐off layer (SOL) during inter‐ELM periods are obtained from a retarding field analyzer (RFA) in the ASDEX Upgrade tokamak. The ion current density measured in the far SOL features large‐amplitude bursts associated with turbulent plasma filaments passing the RFA. These filaments convect plasma to the wall with larger density than the background plasma density. The ions in the filament also have higher impact energies than the background ion impact energies. These observations indicate that a filament‐wall interaction can lead to erosion of the first wall in the burning plasma tokamaks such as ITER (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Triple Probe Measurements Benchmarked by Interferometry in a Pulsed‐Power Plasma
Authors: Mackel F. , Kempkes P. , Tenfelde J. , Ridder S. , Soltwisch H.
Published: January 2013

An electrostatic triple probe was employed to investigate electron densities in a pulsed‐power discharge plasma. The inherent property of electrostatic probes to disturb the plasma is one of the major problems of these diagnostics. The quantification of the systematic error is not straightforward. In order to get non‐intrusive and reliable measurements, a CO2 laser interferometer was set up to determine line integrated‐electron densities. The data are converted into electron number densities by assuming a parabolic density distribution across the plasma column. In a comparison, the triple probe underestimates the electron density (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Determination of the Electron Energy Distribution Function From Langmuir Probe Characteristics Using Non‐Recursive Digital Filters
Authors: Hannemann M.
Published: January 2013

The energy distribution, the mean energy and the density of the electrons of low pressure plasmas may be obtained from the 2nd derivative of a Langmuir probe characteristic. Often numerical methods are used for differentiation. A simple numerical technique is the non‐recursive digital or FIR filtering. Because of noise this process has to comprise also smoothing elements. The best way to achieve this is the successive use of a weakly smoothing interpolation based twofold differentiating filter and a strong smoothing filter. None of the usual smoothing filters exhibits all properties needed in the evaluation of probe characteristics. Window function based FIR filters represent a class of smoothing filters which is especially suited in this context because of its increasing stop band attenuation. A new smoothing filter based on a new parameterized window function is introduced. The testing of this new filter is performed and hints for finding of the filter parameters are given (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The characterization of the nuclear dynamics of syntenin‐2, a PIP2 binding PDZ protein
Authors: Geeraerts Annelies , Hsiu‐Fang Fan , Zimmermann Pascale , Engelborghs Yves
Published: January 2013

Cellular signaling is largely dependent on the presence, that is, assembly/disassembly, of supramolecular complexes. Postsynaptic density protein, Discs‐large, Zona occludens (PDZ) domains play important roles in the assembly of various signaling complexes. Syntenin‐2 (S2) is a PDZ protein that interacts with nuclear phosphatidylinositol 4,5‐bisphosphate (PIP2). Although nuclear lipids emerge as key players in nuclear processes, the global significance of nuclear phosphoinositide‐protein interactions is still poorly understood. Those phosphoinositide‐protein interactions that have been studied in detail appear to have profound physiological effects. To our knowledge none of these were investigated by dynamic studies such as Fluorescence Correlation Spectroscopy (FCS), Fluorescence Cross‐Correlation Spectroscopy (FCCS), or Fluorescence Recovery After Photobleaching (FRAP). Although the exact function of S2 is unknown, siRNA experiments suggest that this PDZ protein plays a role in the organization of nuclear PIP2, cell division, and cell survival. As a consequence of its PIP2 interaction, its reported self‐association in a yeast two‐hybrid study and its speculated interaction with many, yet unidentified, proteins one can hypothesize that S2 plays an important role in cell signaling. Therefore, we studied the dynamics of S2 using FCS, FCCS, and FRAP, utilizing an active truncated form deleted for the first 94 amino acids (S2‐ΔN). We showed that S2‐ΔN self‐associates and is distributed in three groups. One immobile group, one slow diffusing group, which interacts with the nuclear environment and one fast diffusing group, which is not incorporated in high molecular weight complexes. In addition, our FCS and FRAP measurements on S2‐ΔN mutants affected in their PIP2 binding showed that PIP2 plays an important role in the distribution of S2‐ΔN among these groups, and favors the enrichment of S2‐ΔN in the slow diffusing and immobile group. This work indicates that S2 relies on nuclear PIP2 to interact with practically immobile structures, possibly chromatin. © 2013 International Society for Advancement of Cytometry
Interfacial Synthesis of Free‐Standing Metal–Organic Framework Membranes
Authors: Lu Hongyu , Zhu Shiping
Published: January 2013

A method based on a liquid–liquid interfacial coordination mechanism has been developed for the synthesis of free‐standing metal–organic framework (MOF) membranes. MOF precursors, zinc nitrate [Zn(NO3)2] and terephthalic acid (TPA or H2BDC), as well as catalyst triethylamine (TEA), were dissolved in two immiscible solvents, dimethylformamide (DMF) and hexane. The reaction of Zn(NO3)2 and TPA (at a 2:1 molar ratio) in DMF was catalyzed by TEA in hexane at the solvent interface thus forming a free‐standing membrane. A region of reactant concentrations critical to membrane formation was identified; a free‐standing membrane could only be formed in the region of high Zn/TPA and low TEA concentrations. The combination of low Zn/TPA and high TEA concentrations yielded MOF particles that precipitated from DMF. The membranes were characterized by SEM and XRD and found to be asymmetric. SEM results showed that the top layer was particulate, whereas the bottom layer had a sheet‐like morphology, which was further revealed by XRD data as 3D Zn4O(BDC)3 (also known as MOF‐5) and 2D ZnBDC·DMF (MOF‐2) for the top and bottom, respectively. Other transitional zinc–carboxylate structures between the two MOFs, namely Zn3(OH)2(BDC)2 (MOF‐69c) and Zn5(OH)4(BDC)3, were also observed with small signal intensities revealing a transition of coordination modes between zinc ions and BDC groups from 3D to 2D at the membrane cross‐section. This was caused by a change of the TEA diffusion rate during the synthesis process, which might change the pH and alter the membrane growth. From both SEM and XRD characterizations, MOF‐2 is the dominant material in the overall composition. Nitrogen adsorption tests showed an average Langmuir surface area of 709 m2/g for the membrane, demonstrating its potential for gas separation applications.
Computational and Experimental Characterization of a Cagelike Fe15 Polycation
Authors: Hou Yu , Fang Xikui , Kwon Kideok D. , Criscenti Louise J. , Davis Danae , Lambert Tim , Nyman May
Published: January 2013

Polynuclear open‐shell transition‐metal clusters are synthetically challenging, yet fascinating from the perspective of their diverse properties. Iron clusters in particular can exhibit interesting magnetic and electrochemical behaviour, and they can potentially be exploited as models for geochemical processes at iron oxide surfaces. From solvothermal synthesis, we have obtained a cagelike polycationic FeIII cluster, [Fe15Cl6O6(OH)2(C3H6O2)12]+, which features the common polyoxometalate (POM) Keggin ion trimer fragments oriented in an inverse fashion relative to the centre of the cluster. In addition to solid‐state structural characterization, we have examined the magnetic properties, which revealed the presence of antiferromagnetic exchange within the polynuclear system. Electrospray‐ionization mass spectrometry (ESI‐MS) revealed that the Fe9 core of the cluster remains intact upon dissolution, whereas the Fe–Cl2+ caps are more labile. Computational studies agree well with the observed antiferromagnetic character, as well as the HOMO–LUMO bandgap, and also describe these frontier orbitals.
Quantifying different riverbank erosion processes during an extreme flood event
Authors: R. Grove James , Croke Jacky , Thompson Christopher
Published: January 2013

Riverbank erosion is a major contributor to catchment sediment budgets. At large spatial scales data is often restricted to planform channel change, with little information on process distributions and their sediment contribution. This study demonstrates how multi‐temporal LiDAR and high resolution aerial imagery can be used to determine processes and volumes of riverbank erosion at a catchment scale. Remotely sensed data captured before and after an extreme flood event, enabled a digital elevation model of difference (DoD) to be constructed for the channel and floodplain. This meant that: the spatial area that could be assessed was extensive; three‐dimensional forms of bank failures could be mapped at a resolution that enabled process inference; and the volume and rates of different bank erosion processes over time could be assessed. A classification of riverbank mass failures, integrating form and process, identified a total of 437 mass failure polygons throughout the study area. These were interpreted as wet flow mass failures based on the presence of a well defined scarp wall and the absence of failed blocks on the failure floor. The failures appeared to be the result of: bank exfiltration, antecedent moisture conditions preceding the event, and the historic development of the channel. Using one‐dimensional hydraulic modelling to delineate geomorphic features within the main boundary of the macrochannel, an estimated 1 466 322 m2of erosion was interpreted as fluvial entrainment, occurring across catchment areas from 30 to 1668 km2. Only 8% of the whole riverbank planform area was occupied by mass failures, whilst fluvial entrainment covered 33%. A third of the volume of material eroded came from mass failures, even though they occupied 19% of the eroded bank area. The availability of repeat LiDAR surveys, combined with high‐resolution aerial photography, was very effective in erosion process determination and quantification at a large spatial scale. Copyright © 2013 John Wiley & Sons, Ltd.
Role of vascular endothelial growth factor in the pathophysiology of nonalcoholic steatohepatitis in two rodent models
Authors: Coulon Stephanie , Legry Vanessa , Heindryckx Femke , Van Steenkiste Christophe , Casteleyn Christophe , Olievier Kim , Libbrecht Louis , Carmeliet Peter , Jonckx Bart , Stassen Jean-Marie , Van Vlierberghe Hans , Leclercq Isabelle , Colle Isabelle , Geerts Anja
Published: January 2013

The pathophysiology of nonalcoholic steatohepatitis (NASH) should be approached as a multifactorial process. In several stages of NASH, a link between disease progression and hepatic microvasculature changes can be made. In this study we investigated the role of angiogenesis in two mouse models for NASH, and the effect of a preventive and therapeutic antiangiogenic treatment in a diet-induced mouse model for NASH. Protein and RNA levels of angiogenic and inflammatory factors were significantly up-regulated in the liver of C56BL/6 and db/db mice with NASH at different timepoints. To examine the effect of angiogenic factors on the disease progression of NASH, a prevention and treatment study was set up, blocking the placental growth factor (PlGF) or vascular endothelial growth factor receptor 2 (VEGFR2). Our study showed that treatment prevents the progression of NASH by attenuating steatosis and inflammation, both in a preventive and therapeutic setting, thereby confirming the hypothesis that angiogenic factors play an early role in the disease progression from steatosis to NASH. Anti-PlGF (αPlGF) did not significantly improve liver histology. Vascular corrosion casting showed a more disrupted liver vasculature in mice with NASH compared to controls. Treatment with αVEGFR2 showed an improvement of the liver vasculature. Moreover, fat-laden primary hepatocytes treated with αVEGFR2 stored significantly less lipids.

Conclusion:

Our results demonstrate that there is an increased expression of angiogenic factors in the liver in different mouse models for NASH. We found that VEGFR2 blockage attenuates steatosis and inflammation in a diet-induced mouse model for NASH in a preventive and therapeutic setting. Our findings warrant further investigation of the role of angiogenesis in the pathophysiology in NASH.
Molecular subtype and response to dasatinib, an Src/Abl small molecule kinase inhibitor, in hepatocellular carcinoma cell lines in vitro
Authors: Finn Richard S. , Aleshin Alexey , Dering Judy , Yang Peter , Ginther Charles , Desai Amrita , Zhao Danyun , von Euw Erika , Busuttil Ronald W. , Slamon Dennis J.
Published: January 2013

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and is the third leading cause of cancer death worldwide. Recently, the multitargeted kinase inhibitor sorafenib was shown to be the first systemic agent to improve survival in advanced HCC. Unlike other malignancies such as breast cancer, in which molecular subtypes have been clearly defined (i.e., luminal, HER2 amplified, basal, etc.) and tied to effective molecular therapeutics (hormone blockade and trastuzumab, respectively), in HCC this translational link does not exist. Molecular profiling studies of human HCC have identified unique molecular subtypes of the disease. We hypothesized that a panel of human HCC cell lines would maintain molecular characteristics of the clinical disease and could then be used as a model for novel therapeutics. Twenty human HCC cell lines were collected and RNA was analyzed using the Agilent microarray platform. Profiles from the cell lines

in vitro

recapitulate previously described subgroups from clinical material. Next, we evaluated whether molecular subgroup would have predictive value for response to the Src/Abl inhibitor dasatinib. The results demonstrate that sensitivity to dasatinib was associated with a progenitor subtype. Dasatinib was effective at inducing cell cycle arrest and apoptosis in “progenitor-like” cell lines but not in resistant lines.

Conclusion:

These findings suggest that cell line models maintain the molecular background of HCC and that subtype may be important for selecting patients for response to novel therapies. In addition, it highlights a potential role for Src family signaling in this progenitor subtype of HCC.
Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel-Lindau tumor suppressor-dependent HIF-1α inhibition in hepatocellular carcinoma
Authors: Liang Yingjian , Zheng Tongsen , Song Ruipeng , Wang Jiabei , Yin Dalong , Wang Luoluo , Liu Haitao , Tian Lantian , Fang Xiang , Meng Xianzhi , Jiang Hongchi , Liu Jiaren , Liu Lianxin
Published: January 2013

The increasing incidence of hepatocellular carcinoma (HCC) is of great concern not only in the United States but throughout the world. Although sorafenib, a multikinase inhibitor with antiangiogenic and antiproliferative effects, currently sets the new standard for advanced HCC, tumor response rates are usually quite low. An understanding of the underlying mechanisms for sorafenib resistance is critical if outcomes are to be improved. In this study we tested the hypothesis that hypoxia caused by the antiangiogenic effects of sustained sorafenib therapy could induce sorafenib resistance as a cytoprotective adaptive response, thereby limiting sorafenib efficiency. We found that HCCs, clinically resistant to sorafenib, exhibit increased intratumor hypoxia compared with HCCs before treatment or HCCs sensitive to sorafenib. Hypoxia protected HCC cells against sorafenib and hypoxia-inducible factor 1 (HIF-1α) was required for the process. HCC cells acquired increased P-gp expression, enhanced glycolytic metabolism, and increased nuclear factor kappa B (NF-κB) activity under hypoxia. EF24, a molecule having structural similarity to curcumin, could synergistically enhance the antitumor effects of sorafenib and overcome sorafenib resistance through inhibiting HIF-1α by sequestering it in cytoplasm and promoting degradation by way of up-regulating Von Hippel-Lindau tumor suppressor (VHL). Furthermore, we found that sustained sorafenib therapy led to increased intratumor hypoxia, which was associated with sorafenib sensitivity in HCC subcutaneous mice tumor models. The combination of EF24 and sorafenib showed synergistically effects against metastasis both

in vivo

and

in vitro

. Synergistic tumor growth inhibition effects were also observed in subcutaneous and orthotopic hepatic tumors.

Conclusion:

Hypoxia induced by sustained sorafenib treatment confers sorafenib resistance to HCC through HIF-1α and NF-κB activation. EF24 overcomes sorafenib resistance through VHL-dependent HIF-1α degradation and NF-κB inactivation. EF24 in combination with sorafenib represents a promising strategy for HCC.
Improvement of Neurocognitive Function in Responders to an Antiviral Therapy for Chronic Hepatitis C
Authors: Kraus Michael R. , Schäfer Arne , Teuber Gerlinde , Porst Heiner , Sprinzl Kathrin , Wollschläger Sven , Keicher Christian , Scheurlen Michael
Published: January 2013

Earlier studies have suggested neurocognitive impairment in patients with chronic hepatitis C virus (HCV) infection even before liver cirrhosis has developed. Since these deficits might be reversible after successful antiviral therapy, we analyzed the long-term course of neurocognitive parameters in HCV patients with and without successful virus elimination by an interferon-based antiviral treatment. In a multicenter study including 168 HCV patients receiving antiviral therapy (peginterferon alpha-2b and ribavirin) we performed a long-term follow-up of neurocognitive performance before and after treatment. Neurocognitive function was psychometrically assessed using the computer-aided TAP (Test Battery of Attentional Performance). When tested at least 12 months after termination of antiviral treatment, patients with sustained virologic response (SVR) had improved significantly as compared to their pretreatment performance in three of five TAP subtasks (vigilance,

P

< 0.001; shared attention: optical task,

P

< 0.001; working memory,

P

< 0.001). Patients who failed to eradicate the virus, however, showed no significant long-term changes in neurocognitive performance in all five subtasks assessed (0.194 <

P

< 0.804). In the posttreatment evaluation, neurocognitive function was significantly better in responders to the antiviral therapy as compared to nonresponders.

Conclusion

: Successful eradication of HCV leads to a significant improvement of relevant aspects of attentional and neurocognitive performance, indicating that the neurocognitive impairment caused by chronic HCV infection is potentially reversible. This therefore suggests an added therapeutic benefit of antiviral treatment in HCV infection. Improvement of neurocognitive function may be an additional treatment indication in patients with HCV. (HEPATOLOGY 2013;58:497–504)
Health care costs associated with hepatocellular carcinoma: A population-based study
Authors: Thein Hla-Hla , Isaranuwatchai Wanrudee , Campitelli Michael A. , Feld Jordan J. , Yoshida Eric , Sherman Morris , Hoch Jeffrey S. , Peacock Stuart , Krahn Murray D. , Earle Craig C.
Published: January 2013

Although the burden of hepatocellular carcinoma (HCC) is an escalating public health problem, it has not been rigorously estimated within a Canadian context. We conducted a population-based study using Ontario Cancer Registry linked administrative data. The mean net costs of care due to HCC were estimated using a phase of care approach and generalized estimating equations. Using an incidence approach, the mean net costs of care were applied to survival probabilities of HCC patients to estimate 5-year net costs of care and extrapolated to the Canadian population of newly diagnosed HCC patients in 2009. During 2002-2008, 2,341 HCC cases were identified in Ontario. The mean (95% confidence interval [CI]) net costs of HCC care per 30 patient-days (2010 US dollars) were $3,204 ($2,863-$3,545) in the initial phase, $2,055 ($1,734-$2,375) in the continuing care phase, and $7,776 ($5,889-$9,663) in the terminal phase. The mean (95% CI) 5-year net cost of care was $77,509 ($60,410-$94,607) and the 5-year aggregate net cost of care was $106 million ($83-$130 million) (undiscounted). The net costs of patients receiving liver transplantation only and those undergoing surgical resection only were highest in the terminal phase. The net cost of patients receiving radiofrequency ablation as the only treatment was relatively low in the initial phase, and there were no significant differences in the continuing and terminal phases.

Conclusion

: Our findings suggest that costs attributable to HCC are significant in Canada and expected to increase. Our findings of phase-specific cost estimates by resource categories and type of treatment provide information for future cost-effectiveness analysis of potential innovative interventions, resource allocation, and health care budgeting, and public health policy to improve the health of the population. (Hepatology 2013;58:1375–1384)
Immunoglobulin G4+ clones identified by next-generation sequencing dominate the B cell receptor repertoire in immunoglobulin G4 associated cholangitis
Authors: de Buy Wenniger Lucas J. Maillette , Doorenspleet Marieke E. , Klarenbeek Paul L. , Verheij Joanne , Baas Frank , Elferink Ronald P. Oude , Tak Paul P. , de Vries Niek , Beuers Ulrich
Published: January 2013

Immunoglobulin G4 (IgG4)-associated cholangitis (IAC) is a manifestation of the recently discovered idiopathic IgG4-related disease. The majority of patients have elevated serum IgG4 levels and/or IgG4-positive B-cell and plasma cell infiltrates in the affected tissue. We hypothesized that clonally expanded, class-switched IgG4-positive B cells and plasma cells could be causal to these poorly understood phenomena. In a prospective cohort of six consecutive IAC patients, six healthy controls, and six disease controls, we used a novel next-generation sequencing approach to screen the B-cell receptor (BCR) repertoires, in blood as well as in affected tissue, for IgG4+ clones. A full repertoire analysis of the BCR heavy chain was performed using GS-FLX/454 and customized bioinformatics algorithms (>10,000 sequences/sample; clones with a frequency ≥0.5% were considered dominant). We found that the most dominant clones within the IgG+ BCRheavy repertoire of the peripheral blood at baseline were IgG4+ only in IAC patients. In all IAC patients, but none of the controls, IgG4+ BCR clones were among the 10 most dominant BCR clones of any immunoglobulin isotype (IgA, IgD, IgM, and IgG) in blood. The BCR repertoires of the duodenal papilla comprised the same dominant IgG4+ clones as the paired peripheral blood samples. In all IAC patients, after 4 and 8 weeks of corticosteroid therapy the contribution of these IgG4+ clones to the IgG+ repertoire as well as to total BCR repertoire was marginalized, mirroring sharp declines in serum IgG4 titers and regression of clinical symptoms.

Conclusion:

The novel finding of highly abundant IgG4+ BCR clones in blood and tissue of patients with active IAC, which disappear upon corticosteroid treatment, suggests that specific B cell responses are pivotal to the pathogenesis of IAC.
Toll-like receptor 4 activity protects against hepatocellular tumorigenesis and progression by regulating expression of DNA repair protein Ku70 in mice
Authors: Wang Ziyan , Yan Jun , Lin Heng , Hua Fang , Wang Xiaoxing , Liu Hanzhi , Lv Xiaoxi , Yu Jiaojiao , Mi Su , Wang Jiaping , Hu Zhuo-Wei
Published: January 2013

Hepatocellular carcinoma (HCC) is a devastating consequence of chronic inflammatory liver diseases. The goal of this study was to investigate whether Toll-like receptor 4 (TLR4) activity contributes to HCC initiation and progression in mice. A mouse model of diethylnitrosamine (DEN)-induced HCC was generated with wild-type and TLR4 mutant mice, and the development and progression of HCC and senescent responses were assessed using morphologic, immunological, and biochemical criteria. We found that genetic or pharmacologic blocking of TLR4 increased susceptibility to DEN-induced HCC carcinogenesis and progression, which was indicated by increases in number of tumor nodules, tumor volume, and animal death. The enhanced HCC was associated with a broad-spectrum reduction of immune response to DEN liver injury, as indicated by decreases in the liver-infiltrating F4/80+ macrophages, the apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase/NF-κB and IRF3 signaling activities, and the expression of inflammatory cytokines. Suppressed immune networks resulted in a halt of cellular senescence induction in TLR4 mutant liver tissue, which promoted proliferation and suppressed programmed cell death. Moreover, TLR4 mutation resulted in a suppressed capacity of DNA repair due to a decrease in TLR4-medicated expression of DNA repair proteins Ku70/80 in liver tissue and cells. Isotopic expression of Ku70 in TLR4 mutant mice restored senescence and interrupted the positive feedback loop of DNA damage and oxidative stress, which reversed TLR4 mutation–deteriorated HCC carcinogenesis and progression.

Conclusion:

TLR4 plays an integrated defense role against HCC carcinogenesis by enhancing the expression and function of DNA repair protein Ku70. Our studies provide novel insight into TLR4 activity in the regulation of HCC tumorigenesis, which may be useful for the prevention of HCC development.
Risk factors associated with complications in patients with chemotherapy‐induced febrile neutropenia in emergency department
Authors: Lynn Jiun‐Jen , Chen Kuan‐Fu , Weng Yi‐Ming , Chiu Te‐Fa
Published: January 2013

Febrile neutropenia caused by chemotherapy is a frequent medical emergency associated with severe complications in the emergency department (ED). Timely administration of antibiotics is believed to improve patient outcomes for several infectious diseases such as pneumonia and sepsis but has not been thoroughly evaluated for reducing risk of complications in chemotherapy‐induced febrile neutropenia. The aim of this study was to evaluate associations between the risk factors and serious complications in patients presenting to the ED with febrile neutropenia. We reviewed the health information system database to identify a retrospective cohort of patients with febrile neutropenia who visited the ED of a tertiary medical hospital from January to December 2008. Only episodes of febrile neutropenia caused by chemotherapy for underlying cancer were included. Serious complications during hospitalization were defined as unstable hemodynamic status, respiratory distress, altered mental status, newly developed arrhythmia that required intervention, and death during hospitalization. Univariate and multivariate logistic regression analysis was performed to determine potential factors associated with serious complications. We further use decision tree approach to help analyze variables. Among a total of 81 febrile neutropenic episodes in 78 patients, 25 (30.8%) episodes of serious complications were identified. Latency of the first dose of antibiotics, pneumonia and platelet counts ≤ 50,000/mm3 were identified as independent factors associated with serious complications of febrile neutropenia. Earlier administration of antibiotics is associated with fewer complications in patients presenting to the ED with febrile neutropenia. Copyright © 2013 John Wiley & Sons, Ltd.
Optimal age to start preventive measures in women with BRCA1/2 mutations or high familial breast cancer risk
Authors: Tilanus‐Linthorst Madeleine M.A. , Lingsma Hester F. , Evans D. Gareth , Thompson Deborah , Kaas Reinoutje , Manders Peggy , van Asperen Christi J. , Adank Muriel , Hooning Maartje J. , Kwan Lim Gek E. , Eeles Rosalind , Oosterwijk Jan C. , Leach Martin O. , Steyerberg Ewout W.
Published: January 2013

Women from high‐risk families consider preventive measures for breast cancer including screening. Guidelines on screening differ considerably regarding starting age. We investigated whether age at diagnosis in affected relatives is predictive for age at diagnosis. We analyzed the age of breast cancer detection of 1,304 first‐ and second‐degree relatives of 314 BRCA1, 164 BRCA2 and 244 high‐risk participants of the Dutch MRI‐SCreening study. The within‐ and between‐family variance in the relative's age at diagnosis was analyzed with a random effect linear regression model. We compared the starting age of screening based on risk‐group (25 years for BRCA1, 30 years for BRCA2 and 35 years for familial risk), on family history, and on the model, which combines both. The findings were validated in 63 families from the UK‐MARIBS study. Mean age at diagnosis in the relatives varied between families; 95% range of mean family ages was 35–55 in BRCA1‐, 41–57 in BRCA2‐ and 44–60 in high‐risk families. In all, 14% of the variance in age at diagnosis, in BRCA1 even 23%, was explained by family history, 7% by risk group. Determining start of screening based on the model and on risk‐group gave similar results in terms of cancers missed and years of screening. The approach based on familial history only, missed more cancers and required more screening years in both the Dutch and the United Kingdom data sets. Age at breast cancer diagnosis is partly dependent on family history which may assist planning starting age for preventive measures.
Particulate Matter Promotes In Vitro Receptor‐Recognizable Low‐Density Lipoprotein Oxidation and Dysfunction of Lipid Receptors
Authors: Manzano‐León Natalia , Mas‐Oliva Jaime , Sevilla‐Tapia Laura , Morales‐Bárcenas Rocío , Serrano Jesús , O´Neill Marie S. , García‐Cuellar Claudia M. , Quintana Raúl , Vázquez‐López Inés , Osornio‐Vargas Álvaro R.
Published: January 2013

Particulate matter may promote cardiovascular disease, possibly as a consequence of its oxidative potential. Studies using susceptible animals indicate that particulate matter aggravates atherosclerosis by increasing lipid/macrophage content in plaques. Macrophage lipid uptake requires oxidized low‐density lipoprotein and scavenger receptors; same receptors are involved in particulate matter uptake. We studied in vitro particulate matter potential to oxidize low‐density lipoproteins and subsequent cell uptake through scavenger receptors. Particulate matter‐induced low‐density lipoproteins oxidation was evaluated by the thiobarbituric acid assay. Binding/internalization was tested in wild type and scavenger receptor–transfected Chinese hamster ovary cells, and in RAW264.7 cells using fluorescently labeled low‐density lipoproteins. Dose‐dependent binding/internalization only occurred in scavenger receptor–transfected Chinese hamster ovary cells and RAW264.7 cells. Competition binding/internalization using particles showed that particulate matter induced decreased binding (∼50%) and internalization (∼70%) of particle‐oxidized low‐density lipoproteins and native low‐density lipoproteins. Results indicate that particulate matter was capable of oxidizing low‐density lipoproteins, favoring macrophage internalization, and also altered scavenger and low‐density lipoproteins receptor function. © 2012 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:69‐76, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21452
Bovine herpesvirus type 4 infection modulates autophagy in a permissive cell line
Authors: Montagnaro Serena , Ciarcia Roberto , Pagnini Francesco , De Martino Luisa , Puzio Maria Valeria , Granato Giovanna Elvira , Avino Franca , Pagnini Ugo , Iovane Giuseppe , Giordano Antonio
Published: January 2013

Bovine herpesvirus type 4 (BoHV‐4), like other herpesviruses, induces a series of alterations in the host cell that modify the intracellular environment in favor of viral replication, survival and spread. This research examined the impact of BoHV‐4 infection on autophagy in BoHV‐4 infected Madin Darby bovine kidney (MDBK) cells. Protein extracts of BoHV‐4 infected and control MDBK cells were subjected to Western blot. The concentrations of the autophagy and apoptosis‐related proteins Beclin 1, p21, PI3 kinase, Akt1/2, mTOR, phospho mTOR, p62 and the light chain three (LC3) were normalized to the actin level and expressed as the densitometric ratio. Western blot analysis of virus‐infected cells revealed that autophagic degradation pathway was induced in the late phase of BoHV‐4 infection. After 48 h post‐infection the protein LC3II, which is essential for autophagy was found to be markedly increased, while infection of MDBK cells with BoHV‐4 resulted in a depletion of p62 levels. Becline 1, PI3 kinase, Akt1/2 and p21 expression increased between 24 and 48 h post‐infection. Surprisingly, mTOR and its phosphorylated form, which are negative regulators of autophagy, also increased after 24 h post‐infection. In conclusion, our findings suggest that BoHV‐4 has developed mechanisms for modulation of autophagy that are probably part of a strategy designed to enhance viral replication and to evade the immune system. Additional studies on the relationship between autophagy and BoHV‐4 replication and survival, in both lytic and latent replication phases, are needed to understand the role of autophagy in BoHV‐4 pathogenesis. J. Cell. Biochem. 114: 1529–1535, 2013. © 2013 Wiley Periodicals, Inc.
Bis‐μ‐oxo and μ‐η2:η2‐peroxo dicopper complexes studied within (time‐dependent) density‐functional and many‐body perturbation theory
Authors: Rohrmüller M. , Herres‐Pawlis S. , Witte M. , Schmidt W. G.
Published: January 2013

Based on the equilibrium geometries of [Cu2(dbdmed)2O2]2+ and [Cu2(en)2O2]2+ obtained within density‐functional theory, we investigate their molecular electronic structure and optical response. Thereby results from occupation‐constrained as well as time‐dependent DFT (ΔSCF and TDDFT) are compared with Green's function‐based approaches within many‐body perturbation theory such as the GW approximation (GWA) to the quasiparticle energies and the Bethe‐Salpeter equation (BSE) approach to the optical absorption. Concerning the ground‐state energies and geometries, no clear trend with respect to the amount of exact exchange in the DFT calculations is found, and a strong dependence on the basis sets is to be noted. They affect the energy difference between bis‐μ‐oxo and μ‐η2:η2‐peroxo complexes by as much as 0.8 eV (18 kcal/mol). Even stronger, up to 5 eV is the influence of the exchange‐correlation functional on the gap values obtained from the Kohn‐Sham eigenvalues. Not only the value itself but also the trends observed upon the bis‐μ‐oxo to μ‐η2:η2‐peroxo transition are affected. In contrast, excitation energies obtained from ΔSCF and TDDFT are comparatively robust with respect to the details of the calculations. Noteworthy, in particular, is the near quantitative agreement between TDDFT and GWA+BSE for the optical spectra of [Cu2(en)2O2]2+. © 2013 Wiley Periodicals, Inc.
Robust variance estimation in meta‐regression with binary dependent effects
Authors: Tipton Elizabeth
Published: January 2013

Dependent effect size estimates are a common problem in meta‐analysis. Recently, a robust variance estimation method was introduced that can be used whenever effect sizes in a meta‐analysis are not independent. This problem arises, for example, when effect sizes are nested or when multiple measures are collected on the same individuals. In this paper, we investigate the robustness of this method in small samples when the effect size of interest is the risk difference, log risk ratio, or log odds ratio. This simulation study examines the accuracy of 95% confidence intervals constructed using the robust variance estimator across a large variety of parameter values. We report results for both estimations of the mean effect (intercept) and of a slope. The results indicate that the robust variance estimator performs well even when the number of studies is as small as 10, although coverage is generally less than nominal in the slope estimation case. Throughout, an example based on a meta‐analysis of cognitive behavior therapy is used for motivation. Copyright © 2013 John Wiley & Sons, Ltd.
Management of localized gastric cancer
Authors: Blum Mariela A. , Takashi Taketa , Suzuki Akihiro , Ajani Jaffer A.
Published: January 2013

Gastric cancer continues to be a fatal disease with majority of cases presenting in late stages. For patients with advanced disease, we can only recommend palliative therapy. For localized gastric cancer, the approaches vary in various regions of the world. In western countries, preoperative chemotherapy or adjuvant chemo‐radiation is preferred; however in Asia, surgery followed by adjuvant chemotherapy is favored. The extent of the lymph node dissection also varies by region. D2 gastrectomy is difficult to implement in most western countries while it is standardized and is a routine in Asia. We recommend multidisciplinary evaluation of each patient before starting any therapy. The prognosis after resection depends of the pathologic stage. Long‐term survivors are often <50% in the West and <70% in many Asian countries. Regional and systemic recurrences are common. Improved systemic treatments are needed. Detailed studies of molecular biology might uncover novel therapeutic targets and prognostic subgroups. J. Surg. Oncol. 2013;107:265–270. © 2013 Wiley Periodicals, Inc.