bluuebunny/crossref_metadata_2025 huggingface dataset:
Upregulation of OX40 ligand on monocytes contributes to early virological control in patients with chronic hepatitis C
Authors: Zhang Ji‐Yuan , Wu Xiao‐Li , Yang Bin , Wang Yu , Feng Guo‐Hua , Jiang Tian‐Jun , Zeng Qing‐Lei , Xu Xiang‐Sheng , Li Yuan‐Yuan , Jin Lei , Lv Sa , Zhang Zheng , Fu Junliang , Wang Fu‐Sheng
Published: April 2013

Dysfunctional hepatitis C virus (HCV) specific CD4+ T cells are known to contribute to inadequate adaptive immunity in chronic hepatitis C (CHC), although the underlying mechanisms remain largely undefined. In this study, OX40 ligand (OX40L) expression was investigated in 41 treatment‐naïve CHC patients, 20 sustained virological responders and 36 healthy subjects. We observed that OX40L expression was significantly upregulated in peripheral monocytes in CHC patients compared with sustained virological responders and healthy subjects. OX40L upregulation correlated significantly with plasma viral load rather than serum alanine aminotransaminase levels. Furthermore, longitudinal analyses indicated that upregulated OX40L expression on monocytes is closely associated with rapid or early virological responses in patients receiving pegylated IFN‐α/ribavirin treatment. In vitro, HCV core antigen strongly stimulated monocyte expression of OX40L and blockade of TLR2 signaling significantly downregulated OX40L expression. More importantly, elevated OX40L expression was also shown to be closely associated with elevation of the HCV‐specific CD4+ T‐cell response and in vitro blockade of OX40L expressed on monocytes led to impaired CD4+ T‐cell function. These findings, therefore, implicate OX40L expression can be used as a marker to evaluate antiviral treatment efficacy and extend the notion that enhancement of OX40L expression could be a good way for immunotherapy in CHC patients.
Synthesis, Crystal Structures and Properties of the First Lanthanum Selenide Chlorides, LaSeCl and La3Se4Cl
Authors: Schurz Christian M. , Frunder Susanne , Schleid Thomas
Published: April 2013

The first two lanthanum selenide chlorides, LaSeCl and La3Se4Cl, both crystallize orthorhombically in space group Pnma (no. 62). They emerged from reactions of LaCl3 with lanthanum and selenium in appropriate molar ratios at 800–900 °C. Single crystals of the yellow LaSeCl adopt the cotunnite‐type structure of PbCl2 with a = 760.63(5), b = 433.52(3) and c = 910.07(6) pm (Z = 4). The tricapped trigonal prisms [LaSe5Cl4]11– share their triangular faces to form chains that run parallel to the [010] direction and are condensed through caps and common edges to give a complete crystal structure in accord with ∞3{LaSe5/5Cl4/4}. Dark‐red La3Se4Cl exhibits the U3S5‐type structure with a = 1271.98(5), b = 855.84(3) and c = 795.05(2) pm (Z = 4). The chloride anions are located at the Wyckoff position 8d together with selenium showing site occupation factors of 0.5 for both anion types. Bicapped trigonal prisms [LaSe7Cl]12– with (La2)3+ are connected through common faces and corners to form a three‐dimensional framework suited to the embedding of chains of fused tricapped trigonal prisms [LaSe5+1Cl2]11– with (La1)3+ running parallel to [010]. The absorption edge energy of approximately 1.75 eV indicates a wide band‐gap semiconductor that is stable towards air, water and some aqueous bases at different concentrations.
One‐Pot Synthesis of Heteroaryl and Diheteroaryl Ketones through Palladium‐Catalyzed 1,2‐Addition and Oxidation
Authors: Kuriyama Masami , Hamaguchi Norihisa , Sakata Keisuke , Onomura Osamu
Published: April 2013

A synthetic method was developed for the preparation of heteroaryl and diheteroaryl ketones from aldehydes and organoboronic acids through a palladium‐catalyzed 1,2‐addition and oxidation that uses an aryl iodide as the oxidant. This one‐pot process shows high tolerance for a broad range of heterocyclic substrates by using 1.0–3.0 mol‐% of the catalyst that is formed from allylpalladium chloride dimer and a thioether‐imidazolinium chloride. In addition to fine‐tuning the catalytic system, the use of a sterically hindered aryl iodide that has a substituent at the ortho position, such as 2‐iodotoluene, is important to obtain the desired ketones with heterocyclic moieties in good to excellent yields.
Spectroscopic and electrochemical characterization of nanostructured optically transparent carbon electrodes
Authors: Benavidez Tomás E. , Garcia Carlos D.
Published: April 2013

The present paper describes the results related to the optical and electrochemical characterization of thin carbon films fabricated by spin coating and pyrolysis of AZ P4330‐RS photoresist. The goal of this paper is to provide comprehensive information allowing for the rational selection of the conditions to fabricate optically transparent carbon electrodes (OTCE) with specific electrooptical properties. According to our results, these electrodes could be appropriate choices as electrochemical transducers to monitor electrophoretic separations. At the core of this manuscript is the development and critical evaluation of a new optical model to calculate the thickness of the OTCE by variable angle spectroscopic ellipsometry. Such data were complemented with topography and roughness (obtained by atomic force microscopy), electrochemical properties (obtained by cyclic voltammetry), electrical properties (obtained by electrochemical impedance spectroscopy), and structural composition (obtained by Raman spectroscopy). Although the described OTCE were used as substrates to investigate the effect of electrode potential on the real‐time adsorption of proteins by ellipsometry, these results could enable the development of other biosensors that can be then integrated into various CE platforms.
Genetic characterization of selected parasites from people with histories of gastrointestinal disorders using a mutation scanning‐coupled approach
Authors: Koehler Anson V. , Bradbury Richard S. , Stevens Melita A. , Haydon Shane R. , Jex Aaron R. , Gasser Robin B.
Published: April 2013

A SSCP analysis and targeted sequencing approach was used for the genetic characterization of some major pathogens from a cohort of 227 people with histories of gastrointestinal disorders. Genomic DNAs from fecal samples were subjected to PCR‐amplification of regions in the glycoprotein (gp60) or triose phosphate isomerase (tpi) gene, or the second internal transcribed spacer of nuclear ribosomal DNA (ITS‐2). Cryptosporidium, Giardia, and strongylid nematodes were detected in 94, 132 and 12 samples. Cryptosporidium hominis subgenotypes IbA10G2, IdA15G1, IgA17, IgA18, and IfA13G1 were identified in 74.6, 16.9, 5.6, 1.4, and 1.4% of 71 samples, respectively. For Cryptosporidium parvum, subgenotypes IIaA17G2R1 (47.6%) and IIaA18G3R1 (23.8%) were identified in 23 samples. Giardia duodenalis assemblage B (78%) was more common than assemblage A (22%). In addition, DNA of the nematodes Ancylostoma ceylanicum (n = 2), Ancylostoma duodenale (4), Necator americanus (5), and Haemonchus contortus (1) was specifically detected. This is the first report of A. ceylanicum in two persons in Australia and, we provide molecular evidence of H. contortus in a child. This SSCP‐based approach should provide a useful diagnostic and analytical tool for a wide range of pathogens.
The internal concentration of organic substances in fish embryos—A toxicokinetic approach
Authors: Kühnert Agnes , Vogs Carolina , Altenburger Rolf , Küster Eberhard
Published: April 2013

In ecotoxicity assessment, the ambient exposure concentration is typically applied to quantify the toxic potential of xenobiotic substances. However, exposure and organism-related differences in bioconcentration often cause a considerable variability of toxicity data. This can be minimized by using the internal organism concentration, because toxicokinetic modifying factors are considered implicitly. In the present study, the relationship between ambient and internal concentration–time profiles was investigated for zebrafish (Danio rerio) embryos. The aim was to gain a better understanding and interpretation of exposure-based methods using this model organism. For this purpose, a simple and effective approach to determine the internal concentration was developed. Embryos were exposed to a series of 4 neutral organic substances (naphthalene, fluorene, fluoranthene, benz[a]anthracene) of different hydrophobicity for 72 h. The internal and ambient concentrations were measured at 8 to 9 time points. Kinetics of uptake and elimination were modeled using a first-order 1-compartment model. Biotransformation processes appeared to influence the internal concentrations of fluoranthene and benz[a]anthracene after 48 h. The bioconcentration factors (BCFs) obtained are in excellent agreement with those determined in previous studies using radiolabeled substances. The method demonstrated in the present study is a further step toward a refined ecotoxicity assessment using fish embryos, which links toxicity to the chemical concentration within the organism. This system may also be considered as an alternative to animal testing for BCF determination. Environ Toxicol Chem 2013;32:1819–1827. © 2013 SETAC
Comparative pharmaceutical metabolism by rainbow trout (Oncorhynchus mykiss) liver S9 fractions
Authors: Connors Kristin A. , Du Bowen , Fitzsimmons Patrick N. , Hoffman Alex D. , Chambliss C. Kevin , Nichols John W. , Brooks Bryan W.
Published: April 2013

The occurrence of pharmaceuticals in the environment presents a challenge of growing concern. In contrast to many industrial compounds, pharmaceuticals undergo extensive testing prior to their introduction to the environment. In principle, therefore, it may be possible to employ existing pharmacological safety data using biological “read-across” methods to support screening-level bioaccumulation environmental risk assessment. However, few approaches and robust empirical data sets exist, particularly for comparative pharmacokinetic applications. For many pharmaceuticals, the primary cytochrome P450 (CYP) enzymes responsible for their metabolism have been identified in humans. The purpose of the present study was to employ a comparative approach to determine whether rainbow trout biotransform pharmaceuticals known to be substrates for specific human CYPs. Seven compounds were selected based on their primary metabolism in humans by CYP3A4, CYP2D6, or CYP2C9. Five additional test compounds are known to be substrates for multiple CYPs. Metabolism by rainbow trout liver S9 fractions was evaluated using a substrate-depletion approach, which provided an estimate of intrinsic hepatic clearance (CLIN VITRO,INT). An isotope dilution liquid chromatography–tandem mass spectrometry method was employed for quantitation of parent chemical concentrations. Only 2 general CYP substrates demonstrated measurable levels of substrate depletion. No significant biotransformation was observed for known substrates of human CYP2D6, CYP2C9, or CYP3A4. The results of this study provide novel information for therapeutics that fish models are likely to metabolize based on existing mammalian data. Further, these results suggest that pharmaceuticals may possess a greater tendency to bioaccumulate in fish than previously anticipated. Environ Toxicol Chem 2013;32:1810–1818. © 2013 SETAC
Performance of passive samplers for monitoring estuarine water column concentrations: 2. Emerging contaminants
Authors: Perron Monique M. , Burgess Robert M. , Suuberg Eric M. , Cantwell Mark G. , Pennell Kelly G.
Published: April 2013

Measuring dissolved concentrations of emerging contaminants, such as polybrominated diphenyl ethers (PBDEs) and triclosan, can be challenging due to their physicochemical properties resulting in low aqueous solubilities and association with particles. Passive sampling methods have been applied to assess dissolved concentrations in water and sediments primarily for legacy contaminants. Although the technology is applicable to some emerging contaminants, the use of passive samplers with emerging contaminants is limited. In the present study, the performance of 3 common passive samplers was evaluated for sampling PBDEs and triclosan. Passive sampling polymers included low-density polyethylene (PE) and polyoxymethylene (POM) sheets, and polydimethylsiloxane (PDMS)-coated solid-phase microextraction (SPME) fibers. Dissolved concentrations were calculated using measured sampler concentrations and laboratory-derived partition coefficients. Dissolved tri-, tetra-, and pentabrominated PBDE congeners were detected at several of the study sites at very low pg/L concentrations using PE and POM. Calculated dissolved water concentrations of triclosan ranged from 1.7 ng/L to 18 ng/L for POM and 8.8 ng/L to 13 ng/L for PE using performance reference compound equilibrium adjustments. Concentrations in SPME were not reported due to lack of detectable chemical in the PDMS polymer deployed. Although both PE and POM were found to effectively accumulate emerging contaminants from the water column, further research is needed to determine their utility as passive sampling devices for emerging contaminants. Environ Toxicol Chem 2013;32:2190–2196. © 2013 SETAC
Preferences and utilities for health states after treatment for oropharyngeal cancer: Transoral robotic surgery versus definitive (chemo)radiotherapy
Authors: de Almeida John R. , Villanueva Nathaniel L. , Moskowitz Alan J. , Miles Brett A. , Teng Marita S. , Sikora Andrew , Gupta Vishal , Posner Marshall , Genden Eric M.
Published: April 2013

Background

Treatment of oropharyngeal cancer with transoral robotic surgery (TORS) or definitive (chemo)radiotherapy impacts quality of life. Utility scores are needed for quality of life and economic comparisons.

Methods

Fifty healthy subjects and 9 experts reviewed scenarios describing treatment (TORS alone or with adjuvant radiotherapy or chemoradiotherapy [CRT], definitive radiotherapy, and CRT), complications, remission, and recurrences. Utilities were assessed using visual analog scale (VAS) and standard gamble (SG) techniques. Treatments were compared using paired comparisons and demographic variability was assessed.

Results

TORS had higher SG utilities than radiotherapy (p= .001) and CRT (p< .001) and was preferred in paired comparisons (p< .001 for both) for healthy subjects. Utilities did not vary by demographic group and correlated between experts and subjects (VASr= 0.95;p< .001; SGr= 0.97;p< .001).

Conclusion

TORS has higher utility scores than CRT. Utilities can be used for cost–utility analyses. © 2014 Wiley Periodicals, Inc. Head Neck 36: 923–933, 2014
Unusual metastases from tall cell variant of papillary thyroid cancer
Authors: Pagano Loredana , Caputo Marina , Samà Maria Teresa , Zavattaro Marco , Prodam Flavia , Mauri Maria Grazia , Pia Francesco , Alonzo Amedeo , Valente Guido , Aimaretti Gianluca
Published: April 2013

Background

Tall cell variant (TCV) cancer is considered more aggressive than the classic variant of papillary thyroid cancer (PTC). Distant metastases are more common among this variant and affect survival. Little is known about the molecular pattern of this histotype.

Methods

This is a report of 2 cases of unusual metastases from TCV, BRAF V600E‐positive.

Results

A 38‐year‐old woman developed subcutaneous metastases during short‐term follow‐up; at medium‐term follow‐up, the patient showed detectable stimulated serum thyroglobulin without disease evidence at imaging. A 33‐year‐old man presented incidental thymic metastases at time of surgical treatment; this is the first case of not ectopic thymic metastases from PTC.

Conclusion

TCV may present with unusual metastases already during early follow‐up. The more aggressive behavior could be linked to the higher prevalence of BRAF point mutations, but only a long‐term follow‐up might clarify if this association could worsen the prognosis. Moreover, skin metastases have been predictive factors of worse outcome in our patients, but not thymic metastases. © 2013 Wiley Periodicals, Inc. Head Neck 35: E381–E385, 2013
Risk communication discourse among ecological risk assessment professionals and its implications for communication with nonexperts
Authors: Hunka Agnieszka D , Palmqvist Annemette , Thorbek Pernille , Forbes Valery E
Published: April 2013

Risk communication, especially to the general public and end users of plant protection products, is an important challenge. Currently, much of the risk communication the general public receives is via the popular press, and risk managers face the challenge of presenting their decisions and their scientific basis to the general public in an understandable way. Therefore, we decided to explore the obstacles in risk communication, as done by expert risk assessors and managers. Using the discourse analysis framework and readability tests, we studied perspectives of 3 stakeholder groups—regulators, industry representatives, and academics across Europe. We conducted 30 confidential interviews (10 participants in each group), with part of the interview guide focused on communication of pesticide risk to the general public and the ideas experts in the field of risk assessment and management hold of the public perception of pesticides. We used the key informant approach in recruiting our participants. They were first identified as key stakeholders in ecological risk assessment of pesticides and then sampled by means of a snowball sampling technique. In the analysis, first we identified main motifs (themes) in each group, and then we moved to studying length of the sentences and grammar and to uncovering discourses present in the text data. We also used the Flesch Reading Ease test to determine the comprehension difficulty of transcribed interviews. The test is commonly used as a standard for estimating the readability of technical documents. Our results highlight 3 main obstacles standing in the way of effective communication with wider audiences. First of all, ecological risk assessment as a highly technical procedure uses the specific language of ecological risk assessment, which is also highly specialized and might be difficult to comprehend by nonexperts. Second, the idea of existing “expert–lay discrepancy,” a phenomenon described in risk perception studies is visibly present in the experts' opinions. Finally, the communication flow among stakeholders was perceived as flawed, e.g., our participants did not consider themselves fully included in the communication process, despite taking part in many networks. Interestingly, both studies on the role of trust in risk perception, and research on links between daily choices and perceived risk, show that the public is more likely to rely on experts they can trust, than the experts in our study were inclined to think. Integr Environ Assess Manag 2013;9:616–622. © 2013 SETAC
Synthesis of Some New Benzo[b][1,4]diazepine Based Heterocycles
Authors: El‐Azab Islam H.
Published: April 2013

Preparation of 4‐chloro‐3H‐benzo[b][1,4]diazepine‐2‐carbaldehyde 5, which is used as a key intermediate in the synthesis of chalcones derivatives, via its condensation with some aromatic acetophenone derivatives under ethanol piperidine condition was described. Also illustrated was the reaction of such chalcones with available nucleophilics and reagents of active methylene group to afford new series of fused and isolated pyrazoles, isoxazolines pyrimidines, pyridines, triazolo[1,5‐a]pyrimidines, benzo[1,4]oxa(thia)zepines, and pyrido[1,2‐a]benzimidazoles incorporating 4‐chloro‐3H‐benzo[b][1,4]diazepine moiety, which have a potential pharmaceutical interest. Furthermore, condensation reaction of 4‐chloro‐3H‐benzo[b][1,4]diazepine‐2‐carbaldehyde with aromatic amine derivatives to afford the Schiff's bases was described. The C═N double bond of the latter compounds has been reacted with chloroketene to give β‐lactams and with sulfanylacetic acid to give the 2‐(4‐oxo‐1,3‐thiazolidinyl)‐substituted derivative. The structures of the newly prepared compounds were established by elemental analysis, IR, MS, and 1H NMR spectral analysis.
Anti‐inflammatory/regulatory cytokine microenvironment mediated by IL‐4 and IL‐10 coordinates the immune response in hemophilia A patients infected chronically with Hepatitis C virus
Authors: Pimentel João Paulo , Chaves Daniel Gonçalves , Araújo Ana Ruth Silva , de Araújo Erbênia Maria Martins , da Silva Fraporti Liziara , Neves Walter Luiz Lima , Tarragô Andrea Monteiro , Torres Katia Luz , Gentz Solange Henschke Lima , Teixeira‐Carvalho Andréa , Martins‐Filho Olindo Assis , Malheiro Adriana
Published: April 2013

In the past decades patients with hemophilia were infected commonly by hepatitis C virus (HCV) and a significant number of patients are infected chronically. Focusing on the role of the immune system for controlling and or maintaining HCV infection, the leukocyte and cytokine profiles of peripheral blood from hemophilia A patients and other patients with and without HCV infection were studied. The results demonstrated that hemophilia A is characterized by a general state of circulating leukocytes activation along with an overall increase in the frequency of IL‐6 and IL‐10 with decrease of IL‐8 and IL‐12. HCV infection of patients with hemophilia A does not influence further the activation state of circulating leukocytes but is accompanied by lower levels of alanine transaminase (ALT) and a prominent anti‐inflammatory/regulatory serum cytokine pattern, mediated by IL‐4 and IL‐10. Additionally, the results demonstrated that hemophilia A patients infected with HCV displaying No/Low antibody response to C33c and C22 have significant lower viral load and higher serum levels of IL‐12 and IL‐4. This finding suggests that the differential RIBA reactivity to C33c/C22 HCV core proteins may have a putative value as a prognostic biomarker for the infection in hemophilia A patients. J. Med. Virol. 85: 1009–1018, 2013. © 2013 Wiley Periodicals, Inc.
Tourism and Long‐run Economic Growth in Aruba
Authors: Ridderstaat Jorge , Croes Robertico , Nijkamp Peter
Published: April 2013

This study examines the long‐run relationship between tourism development and economic growth in a small island destination. Determining whether the nature of the relationship is unidirectional or bidirectional provides insightful information as to policies to be implemented. This information is crucial in a resource‐poor environment, such as a small island destination. The study employs an econometric methodology consisting of unit root testing, co‐integration analysis, vector error correction modeling and Granger causality testing. Results confirm the reciprocal hypothesis. The policy implication is that resource allocation supporting both the tourism and tourism‐related industries could benefit both tourism development and economic growth. Copyright © 2013 John Wiley & Sons, Ltd.
Patterning Surfaces for Controlled Platelet Adhesion and Detection of Dysfunctional Platelets
Authors: Ye Wei , Shi Qiang , Wong Shing‐Chung , Hou Jianwen , Shi Hengchong , Yin Jinghua
Published: April 2013

Platelets play a fundamental role in thrombus formation and in the pathogenesis of arterial thrombosis. Patterning surfaces for controlled platelet adhesion paves the way for adhesion and activation mechanisms in platelets and detection of platelet functional defects. Here, a new and simple method based on controlled polymerization of 2‐methacryloyloxyethyl phosphorylcholine (MPC) on the surface of styrene‐block‐(ethylene‐co‐butylene)‐block‐styrene (SEBS) is shown. The competition between polymerization and degradation enables platelet adhesion on SEBS to be switched on and off. The adhesive sites of the platelets can be down to single cell level, and the dysfunctional platelets can be quantitatively detected.

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Benzo[1,2‐b:4,5‐b′]dithiophene‐alt‐terthiophene Copolymers Containing Styryl‐Triphenylamine Side Chains: Synthesis and Photovoltaic Performance Optimization with Fullerene Acceptors
Authors: Wang Xitian , Zhang Zhi‐Guo , Tang Wenli , Shen Suling , Liu Guo , Chi Dan , Li Yongfang , Wang Jizheng
Published: April 2013

A new two‐dimensional‐conjugated polymer (PBDTT3‐TPA) containing benzodithiophene (BDT) and a side chain isolation comonomer is designed and synthesized. Interestingly, PBDTT3‐TPA is compatible with higher lowest unoccupied molecular level (LUMO) acceptors of indene‐C60 bisadduct (ICBA), and polymer solar cells based on PBDTT3‐TPA/ICBA show an open‐circuit voltage (VOC) of ca. 0.80 V and a power conversion efficiency of 2.48% under AM1.5G illumination of at 100 mW cm−2. Furthermore, the energy loss in the corresponding fullerene acceptor devices is discussed, and the increase in the observed VOC is explained quantitatively by the up‐shifted LUMO energy of ICBA (0.17 eV) and the reduced saturation current (JSO) in the blends.

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Existence results of periodic solutions for third‐order nonlinear singular differential equation
Authors: Ren Jingli , Cheng Zhibo , Chen Yueli
Published: April 2013

Using Green's function for third‐order differential equation and some fixed‐point theorems, i.e., Leray‐Schauder alternative principle and Schauder's fixed point theorem, we establish three new existence results of periodic solutions for nonlinear third‐order singular differential equation, which extend and improve significantly existing results in the literature.
Point value characterizations and related results in the full Colombeau algebras \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}${{\mathcal {G}}^e(\Omega )}$\end{document} and \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}${{\mathcal {G}}^d(\Omega )}$\end{document}
Authors: Nigsch Eduard A.
Published: April 2013

We present a point value characterization for elements of the elementary full Colombeau algebra \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}${\mathcal {G}}^e(\Omega )$\end{document} and the diffeomorphism invariant full Colombeau algebra \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathcal {G}^d(\Omega )$\end{document}. Moreover, several results from the special algebra \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}${\mathcal {G}}^s(\Omega )$\end{document} about generalized numbers and invertibility are extended to the elementary full algebra.
Clinical response to chemotherapy in oesophageal adenocarcinoma patients is linked to defects in mitochondria
Authors: Aichler Michaela , Elsner Mareike , Ludyga Natalie , Feuchtinger Annette , Zangen Verena , Maier Stefan K , Balluff Benjamin , Schöne Cédrik , Hierber Ludwig , Braselmann Herbert , Meding Stephan , Rauser Sandra , Zischka Hans , Aubele Michaela , Schmitt Manfred , Feith Marcus , Hauck Stefanie M , Ueffing Marius , Langer Rupert , Kuster Bernhard , Zitzelsberger Horst , Höfler Heinz , Walch Axel K
Published: April 2013

Chemotherapeutic drugs kill cancer cells, but it is unclear why this happens in responding patients but not in non‐responders. Proteomic profiles of patients with oesophageal adenocarcinoma may be helpful in predicting response and selecting more effective treatment strategies. In this study, pretherapeutic oesophageal adenocarcinoma biopsies were analysed for proteomic changes associated with response to chemotherapy by MALDI imaging mass spectrometry. Resulting candidate proteins were identified by liquid chromatography–tandem mass spectrometry (LC–MS/MS) and investigated for functional relevance in vitro. Clinical impact was validated in pretherapeutic biopsies from an independent patient cohort. Studies on the incidence of these defects in other solid tumours were included. We discovered that clinical response to cisplatin correlated with pre‐existing defects in the mitochondrial respiratory chain complexes of cancer cells, caused by loss of specific cytochrome c oxidase (COX) subunits. Knockdown of a COX protein altered chemosensitivity in vitro, increasing the propensity of cancer cells to undergo cell death following cisplatin treatment. In an independent validation, patients with reduced COX protein expression prior to treatment exhibited favourable clinical outcomes to chemotherapy, whereas tumours with unchanged COX expression were chemoresistant. In conclusion, previously undiscovered pre‐existing defects in mitochondrial respiratory complexes cause cancer cells to become chemosensitive: mitochondrial defects lower the cells' threshold for undergoing cell death in response to cisplatin. By contrast, cancer cells with intact mitochondrial respiratory complexes are chemoresistant and have a high threshold for cisplatin‐induced cell death. This connection between mitochondrial respiration and chemosensitivity is relevant to anticancer therapeutics that target the mitochondrial electron transport chain. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Electro‐optical limits of organic LED investigated through temperature and applied field dependencies
Authors: Nenna G. , De Girolamo Del Mauro A. , Miscioscia R. , Fasolino T. , Pandolfi G. , Minarini C.
Published: April 2013

In this article, the electrical and optical properties of organic light emitting diodes (OLEDs) are analyzed, deriving the devices limits at high applied electric fields and at different temperatures. The temperature failures zones have been evaluated, studying the temperature‐dependent electrical properties of the OLEDs by means of barrier parameter evaluation, and observing the charge carrier injection at metal/organic interfaces. In particular, for different device thicknesses, it is possible to detect both the surface glass transition point and the complete bulk glass transition of the amorphous organic material employed eventually correlating such mechanisms to device limitations at high applied field. POLYM. COMPOS., 34:1477–1482, 2013. © 2013 Society of Plastics Engineers
The relation between prospective memory and working memory: Evidence from event‐related potential data
Authors: Wang Ya , Cao Xiao‐yan , Cui Ji‐fang , Shum David H. K. , Chan Raymond C. K.
Published: April 2013

Event‐related potentials were used in this study to investigate the neural correlates of prospective memory and whether working memory is involved in prospective remembering. Thirty undergraduate or graduate students participated in the study. All participants completed a working memory test, namely, the Chinese Letter‐Number Span Test, and were divided into two groups: the longer and shorter working memory span groups. They also undertook a prospective memory task while electrophysiological data were recorded. The results showed that participants in the longer working memory span group had shorter reaction times and smaller amplitudes in prospective positivity than participants in the shorter working memory span group. The results suggested that working memory resources are involved in the intention retrieval process of prospective remembering.
Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell‐free DNA from maternal plasma
Authors: Mazloom Amin R. , Džakula Željko , Oeth Paul , Wang Huiquan , Jensen Taylor , Tynan John , McCullough Ron , Saldivar Juan‐Sebastian , Ehrich Mathias , van den Boom Dirk , Bombard Allan T. , Maeder Margo , McLennan Graham , Meschino Wendy , Palomaki Glenn E. , Canick Jacob A. , Deciu Cosmin
Published: April 2013

Objective

Whole‐genome sequencing of circulating cell free (ccf) DNA from maternal plasma has enabled noninvasive prenatal testing for common autosomal aneuploidies. The purpose of this study was to extend the detection to include common sex chromosome aneuploidies (SCAs): [47,XXX], [45,X], [47,XXY], and [47,XYY] syndromes.

Method

Massively parallel sequencing was performed on ccf DNA isolated from the plasma of 1564 pregnant women with known fetal karyotype. A classification algorithm for SCA detection was constructed and trained on this cohort. Another study of 411 maternal samples from women with blinded‐to‐laboratory fetal karyotypes was then performed to determine the accuracy of the classification algorithm.

Results

In the training cohort, the new algorithm had a detection rate (DR) of 100% (95%CI: 82.3%, 100%), a false positive rate (FPR) of 0.1% (95%CI: 0%, 0.3%), and nonreportable rate of 6% (95%CI: 4.9%, 7.4%) for SCA determination. The blinded validation yielded similar results: DR of 96.2% (95%CI: 78.4%, 99.8%), FPR of 0.3% (95%CI: 0%, 1.8%), and nonreportable rate of 5% (95%CI: 3.2%, 7.7%) for SCA determination

Conclusion

Noninvasive prenatal identification of the most common sex chromosome aneuploidies is possible using ccf DNA and massively parallel sequencing with a high DR and a low FPR. © 2013 John Wiley & Sons, Ltd.
Beyond Statins: Lipid Management to Reduce Cardiovascular Risk
Authors: Schuck Robert N. , Mendys Philip M. , Simpson Ross J.
Published: April 2013

The discovery that elevated total cholesterol levels and the subsequent understanding that low‐density lipoprotein cholesterol levels are associated with higher risk for cardiovascular disease (CVD) has led to the development of lipid management strategies that seek to reduce the burden of CVD. Although substantive progress has been made in reducing death and cardiovascular events, questions remain regarding the optimal approach to further reduce CVD‐associated death and disability. Based on current evidence, statins are the clear first‐line agents for the management of hyperlipidemia in patients at high risk for cardiovascular events. However, due to the failure of recent clinical trials evaluating antihyperlipidemic drugs, the most appropriate lipid management strategy in patients who cannot tolerate statin therapy or who warrant antihyperlipidemic therapies in addition to statins is a major therapeutic controversy. In this review, we summarize the clinical trial evidence evaluating the efficacy of second‐line antihyperlipidemic drug classes for reducing cardiovascular risk, provide recommendations for appropriate use of nonstatin lipid‐altering drugs, and identify key areas of future research to support evidence‐based lipid management. Given the complexity, magnitude, and burden of CVD, opportunities to improve processes of care and identify new therapeutic options clearly exist.
MgZnO avalanche photodetectors realized in Schottky structures
Authors: Yu J. , Shan C. X. , Liu J. S. , Zhang X. W. , Li B. H. , Shen D. Z.
Published: April 2013

MgZnO‐based ultraviolet avalanche photodetectors (APDs) have been fabricated from Au/MgO/Mg0.44Zn0.56O/MgO/Au Schottky structures. The carrier avalanche multiplication is realized via an impact ionization process occurring in the MgO layer under relatively large electric field. The APDs exhibit an avalanche gain of 587 at 31 V bias, and the response speed of the APDs is in the order of microseconds.

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(© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the critical technological issues of friction stir welding lap joints of dissimilar aluminum alloys
Authors: Velotti C. , Astarita A. , Squillace A. , Ciliberto S. , Villano M. G. , Giuliani M. , Prisco U. , Montuori M. , Giorleo G. , Bellucci F.
Published: April 2013

In this article, friction stir welded lap joints of innovative dissimilar aluminum alloys have been produced and tested to investigate the feasibility of using this joining technique in this configuration. The introduction of both this new welding technique alloys, such as AA 2198, could allow making lighter and stronger structures. Some experiments, carried out previously, have shown that the fixturing device, the tool geometry, and the tilt angle play a significant role in the joint soundness. A wide experimental characterization has been carried out on friction stir welded lap joints of AA 7075 T6 extrudes to AA 2198 T351 rolled plates. The results attained are allowed to put in evidence some critical issues on the investigated configuration and can be considered as a further acquired knowledge in the understanding and the design of friction stir processes. Copyright © 2013 John Wiley & Sons, Ltd.
Robustness of methods for blinded sample size re‐estimation with overdispersed count data
Authors: Schneider Simon , Schmidli Heinz , Friede Tim
Published: April 2013

Counts of events are increasingly common as primary endpoints in randomized clinical trials. With between‐patient heterogeneity leading to variances in excess of the mean (referred to as overdispersion), statistical models reflecting this heterogeneity by mixtures of Poisson distributions are frequently employed. Sample size calculation in the planning of such trials requires knowledge on the nuisance parameters, that is, the control (or overall) event rate and the overdispersion parameter. Usually, there is only little prior knowledge regarding these parameters in the design phase resulting in considerable uncertainty regarding the sample size. In this situation internal pilot studies have been found very useful and very recently several blinded procedures for sample size re‐estimation have been proposed for overdispersed count data, one of which is based on an EM‐algorithm. In this paper we investigate the EM‐algorithm based procedure with respect to aspects of their implementation by studying the algorithm's dependence on the choice of convergence criterion and find that the procedure is sensitive to the choice of the stopping criterion in scenarios relevant to clinical practice. We also compare the EM‐based procedure to other competing procedures regarding their operating characteristics such as sample size distribution and power. Furthermore, the robustness of these procedures to deviations from the model assumptions is explored. We find that some of the procedures are robust to at least moderate deviations. The results are illustrated using data from the US National Heart, Lung and Blood Institute sponsored Asymptomatic Cardiac Ischemia Pilot study. Copyright © 2013 John Wiley & Sons, Ltd.
Large Dynamic Range Digital Nanodot Gradients of Biomolecules Made by Low‐Cost Nanocontact Printing for Cell Haptotaxis
Authors: Ricoult Sébastien G. , Pla‐Roca Mateu , Safavieh Roozbeh , Lopez‐Ayon G. Monserratt , Grütter Peter , Kennedy Timothy E. , Juncker David
Published: April 2013

A novel method is introduced for ultrahigh throughput and ultralow cost patterning of biomolecules with nanometer resolution and novel 2D digital nanodot gradients (DNGs) with mathematically defined slopes are created. The technique is based on lift‐off nanocontact printing while using high‐resolution photopolymer stamps that are rapidly produced at a low cost through double replication from Si originals. Printed patterns with 100 nm features are shown. DNGs with varying spacing between the dots and a record dynamic range of 4400 are produced; 64 unique DNGs, each with hundreds of thousands of dots, are inked and printed in 5.5 min. The adhesive response and haptotaxis of C2C12 myoblast cells on DNGs demonstrated their biofunctionality. The great flexibility in pattern design, the massive parallel ability, the ultra low cost, and the extreme ease of polymer lift‐off nanocontact printing will facilitate its use for various biological and medical applications.
S‐layer Coated Emulsomes as Potential Nanocarriers
Authors: Ucisik Mehmet H. , Küpcü Seta , Debreczeny Monika , Schuster Bernhard , Sleytr Uwe B.
Published: April 2013

The present study introduces a novel nanocarrier system comprising lipidic emulsomes and S‐layer (fusion) proteins as functionalizing tools coating the surface. Emulsomes composed of a solid tripalmitin core and a phospholipid shell are created reproducibly with an average diameter of approximately 300 nm using temperature‐controlled extrusion steps. Both wildtype (wt) and recombinant (r) S‐layer protein SbsB of Geobacillus stearothermophilus PV72/p2 are capable of forming coherent crystalline envelope structures with oblique (p1) lattice symmetry, as evidenced by transmission electron microscopy. Upon coating with wtSbsB, positive charge of emulsomes shifts to a highly negative zeta potential, whereas those coated with rSbsB become charge neutral. This observation is attributed to the presence of a negatively charged glycan, the secondary cell wall polymer (SCWP), which is associated only with wtSbsB. The present study shows for the first time the ability of recombinant and wildtype S‐layer proteins to cover the entire surface of emulsomes with its characteristic crystalline lattice. Furthermore, in vitro cell culture studies reveal that S‐layer coated emulsomes can be uptaken by human liver carcinoma cells (HepG2) without showing any significant cytotoxicity over a wide range of concentrations. The utilization of S‐layer fusion proteins equipped in a nanopatterned fashion by identical or diverse functions may lead to further development of emulsomes in nanomedicine, especially for drug delivery and targeting.
Direct Laser‐Patterned Micro‐Supercapacitors from Paintable MoS2 Films
Authors: Cao Liujun , Yang Shubin , Gao Wei , Liu Zheng , Gong Yongji , Ma Lulu , Shi Gang , Lei Sidong , Zhang Yunhuai , Zhang Shengtao , Vajtai Robert , Ajayan Pulickel M.
Published: April 2013

Micrometer‐sized electrochemical capacitors have recently attracted attention due to their possible applications in micro‐electronic devices. Here, a new approach to large‐scale fabrication of high‐capacitance, two‐dimensional MoS2 film‐based micro‐supercapacitors is demonstrated via simple and low‐cost spray painting of MoS2 nanosheets on Si/SiO2 chip and subsequent laser patterning. The obtained micro‐supercapacitors are well defined by ten interdigitated electrodes (five electrodes per polarity) with 4.5 mm length, 820 μm wide for each electrode, 200 μm spacing between two electrodes and the thickness of electrode is ∼0.45 μm. The optimum MoS2‐based micro‐supercapacitor exhibits excellent electrochemical performance for energy storage with aqueous electrolytes, with a high area capacitance of 8 mF cm−2 (volumetric capacitance of 178 F cm−3) and excellent cyclic performance, superior to reported graphene‐based micro‐supercapacitors. This strategy could provide a good opportunity to develop various micro‐/nanosized energy storage devices to satisfy the requirements of portable, flexible, and transparent micro‐electronic devices.
Nanoscale Size Control of Protein Aggregates
Authors: Pedersen Christian , Vallhov Helen , Engqvist Håkan , Scheynius Annika , Strømme Maria
Published: April 2013

Herein, a novel method to synthesize soluble, sub‐micrometer sized protein aggregates is demonstrated by mixing native and denatured proteins without using bacteria and contaminating proteins. Ovalbumin (OVA) is employed as a model protein. The average size of the formed aggregates can be controlled by adjusting the fraction of denatured protein in the sample and it is possible to make unimodal size distributions of protein aggregates. OVA aggregates with a size of ∼95 nm are found to be more immunogenic compared to native OVA in a murine splenocyte proliferation assay. These results suggest that the novel method of engineering size specific sub‐micrometer sized aggregates may constitute a potential route to increasing the efficacy of protein vaccines. The protein aggregates may also be promising for use in other applications including the surface functionalization of biomaterials and as industrial catalysis materials.
My Father, My Grandfather
Authors: Masamune Takako , Masamune Hiroko , Masamune Tohoru
Published: April 2013

Note from the Editor:

It is with great pleasure and enthusiasm that I introduce this essay which accompanies the publication of the fourth segment of the Tetsuo Nozoe Autograph Books. In the conceptualization stages of this project—which shall appear in 15 consecutive issues of The Chemical Record as well as have a significant internet presence—I proposed to my colleagues Eva Wille and Brian Johnson that each segment be accompanied with a specially invited essay or perspective. This proposal was immediately and enthusiastically accepted. To both celebrate the life and warmth of Tetsuo Nozoe, I can hardly imagine a more appropriate essay than one written by two of his grandchildren and one of his own children! I thank the Masamune Family for their touching contribution to this project. The Nozoe Autograph Books and all the accompanying essays, including this essay, are open access for at least a three‐year period at: http://www.tcr.wiley‐vch.de/nozoe.

 Jeffrey I. Seeman

 Guest Editor,

 University of Richmond

 Richmond, Virginia 23173, USA
The Challenges of Chinese Outward Investment in Developed Countries: The Case of CITIC Pacific's Sino Iron Project in Australia
Authors: Sun Sunny Li , Zhang Yanli , Chen Zhu
Published: April 2013

Sino Iron is a multibillion‐dollar magnetite iron ore project located in Cape Preston, a remote region in western Australia. Acquired by China International Trust and Investment Company (CITIC) Pacific for 100 percent of its equity, Sino Iron is China's most significant investment in the Australian natural resources sector and is the largest magnetite mining and processing operation under construction in Australia. Written from the perspective of Dr. Hua Dongyi, the executive chairman of the Sino Iron project, this case highlights the significant challenges faced by Chinese companies venturing overseas, including government relations, labor relations, and social and environmental responsibility. © 2013 Wiley Periodicals, Inc.

This research was supported in part by the Bloch Summer Research Grants, University of Missouri–Kansas City. We appreciate helpful comments from the three anonymous reviewers, Professors Mike W. Peng, and John Cantwell. The views expressed are those of the authors and not those of the sponsor.
Morphogenesis of simple leaves: regulation of leaf size and shape
Authors: Rodriguez Ramiro E. , Debernardi Juan M. , Palatnik Javier F.
Published: April 2013

Plants produce new organs throughout their life span. Leaves first initiate as rod‐like structures protruding from the shoot apical meristem, while they need to pass through different developmental stages to become the flat organ specialized in photosynthesis. Leaf morphogenesis is an active process regulated by many genes and pathways that can generate organs with a wide variety of sizes and shapes. Important differences in leaf architecture can be seen among different species, but also in single individuals. A key aspect of leaf morphogenesis is the precise control of cell proliferation. Modification or manipulation of this process may lead to leaves with different sizes and shapes, and changes in the organ margins and curvature. Many genes required for leaf development have been identified in Arabidopsis thaliana, and the mechanisms underlying leaf morphogenesis are starting to be unraveled at the molecular level. WIREs Dev Biol 2014, 3:41–57. doi: 10.1002/wdev.115

This article is categorized under:

Plant Development > Vegetative Development

Plant Development > Cell Growth and Differentiation