bluuebunny/crossref_metadata_2025 huggingface dataset:
Observational‐ and model‐based trends and projections of extreme precipitation over the contiguous United States
Authors: Janssen Emily , Wuebbles Donald J. , Kunkel Kenneth E. , Olsen Seth C. , Goodman Alex
Published: January 2014

Historical and projected trends in extreme precipitation events are examined in Coupled Model Intercomparison Project 5 (CMIP5) models and observations, over the contiguous United States (CONUS), using several approaches. This study updates earlier studies that have used the extreme precipitation index (EPI) to assess observations and goes further by using the EPI to evaluate available climate model simulations. An increasing trend over the CONUS was found in the EPI, with large differences among seven subregions of the United States. Median of CMIP5 simulations also finds an increasing trend in the EPI, but with a smaller magnitude than the observations. Model spread is large and in most cases bigger than the model signal itself. Statistically significant (95th confidence level) increasing trends in the observational‐based EPI occur over the Midwest and Eastern regions, while most decreasing trends occur over Western regions. Some models give negative correlation coefficients relative to observations. However, some ensemble members, for most models, show correlation coefficients greater than 0.5. Projections of extreme precipitation event frequency, for representative concentration pathway (RCP) scenarios 4.5 and 8.5, show increasing trends over the CONUS. Both scenarios give a steady increase throughout the period but the RCP 4.5 signal is smaller in magnitude. Overall, the RCP scenarios show an increase across all regions with the exception of some variability between decades in some regions for RCP 4.5. For the CONUS model spread is smaller than the projected signal. Regional analyses show overall agreement among models of a future increase in extreme precipitation event frequency over most regions.
Impact of losing and gaining streamflow conditions on hyporheic exchange fluxes induced by dune‐shaped bed forms
Authors: Fox Aryeh , Boano Fulvio , Arnon Shai
Published: January 2014

The exchange of water between the surface and subsurface environments plays a crucial role in hydrological, biogeochemical, and ecological processes. The exchange of water is driven by the local morphology of the streambed (hyporheic exchange) and the regional forcing of a large‐scale hydraulic gradient, which results in losing or gaining flow conditions. We measured the effects of losing and gaining flow conditions on hyporheic exchange fluxes in a sandy streambed using a novel laboratory flume system (640 cm long and 30 cm wide) under a combination of average overlying velocities and losing/gaining fluxes. Hyporheic exchange fluxes were analyzed based on a new conceptual framework. This combination of experimental observations and modeling revealed that hyporheic exchange fluxes under losing and gaining flow conditions are similar. Because interfacial transport increases proportionally to the square of the overlying velocity and linearly with increasing fluxes of losing and gaining conditions in the sand bed, the hyporheic exchange flux becomes smaller when the losing or gaining flux increases. Thus, losing and gaining flow conditions become the dominant mechanisms of water exchange at a certain flux, which depends on the competitive interaction between the overlying velocity in the stream and the losing/gaining fluxes.
Ultrasensitive Telomerase Activity Detection in Circulating Tumor Cells Based on DNA Metallization and Sharp Solid‐State Electrochemical Techniques
Authors: Wu Li , Wang Jiasi , Ren Jinsong , Qu Xiaogang
Published: January 2014

Being considered a “liquid biopsy”, circulating tumor cell (CTC) quantification is of great interest for evaluating cancer dissemination, predicting patient prognosis, and also for the evaluation of therapeutic treatments, representing a reliable potential alternative to invasive biopsies and subsequent proteomic and functional genetic analysis. Compared to a biopsy, the gold standard of current cancer diagnosis, an important characteristic of a blood test is that it is safe and can be performed at many points during the disease, allowing the development of appropriate therapy modifications and potentially improving patient's quality of life. In this work, an ultrasensitive electrochemical telomerase activity‐sensing strategy is presented that utilizes DNA‐templated deposition of silver nanoparticles as electroactive labels through a highly sharp solid‐state Ag/AgCl reaction with DNA exonuclease III‐assisted background current suppression. This nanoparticle‐mediated signal amplification resulted in significantly decreased detection limit, which is better than the vast majority of reported methods and achieves a sensitivity comparable to the conventional telomeric repeat amplification protocol (TRAP). This work may pave a new PCR‐free way for the detection of telomerase activity in CTCs via a noninvasive routine blood test for point‐of‐care diagnosis and individualized treatment of cancer.
Clickable, Photodegradable Hydrogels to Dynamically Modulate Valvular Interstitial Cell Phenotype
Authors: Magin Chelsea M. , Alge Daniel L. , Gould Sarah T. , Anseth Kristi S.
Published: January 2014

Biophysical cues are widely recognized to influence cell phenotype. While this evidence was established using static substrates, there is growing interest in creating stimulus‐responsive biomaterials that better recapitulate the dynamic extracellular matrix. Here, a clickable, photodegradable hydrogel substrate that allows the user to precisely control substrate elasticity and topography in situ is presented. The hydrogels are synthesized by reacting an 8‐arm poly(ethylene glycol) alkyne with an azide‐functionalized photodegradable crosslinker. The utility of this platform by exploiting its photoresponsive properties to modulate the phenotype of porcine aortic valvular interstitial cells (VICs) is demonstrated. First, VIC phenotype is monitored, in response to initial substratum modulus and static topographic cues. Higher modulus (E ≈ 15 kPa) substrates induce higher levels of activation (≈70% myofibroblasts) versus soft (E ≈ 3 kPa) substrates (≈20% myofibroblasts). Microtopographies that induce VIC alignment and elongation on low modulus substrates also stimulate activation. Finally, VIC phenotype is monitored in response to sequential in situ manipulations. The results illustrate that VIC activation on stiff surfaces (≈70% myofibroblasts) can be partially reversed by reducing surface modulus (≈30% myofibroblats) and subsequently re‐activatedby anisotropic topographies (≈60% myofibroblasts). Such dynamic substrates afford unique opportunities to decipher the complex role of matrix cues on the plasticity of VIC activation.
Microfluidics Expands the Zebrafish Potentials in Pharmaceutically Relevant Screening
Authors: Chen Chia‐Yuan , Cheng Chao‐Min
Published: January 2014

The objective of this study is to enlarge the impact of microfluidics on the pharmaceutical industry by highlighting the reported scientific work on the synergistic relationship between zebrafish and microfluidics, and furthering that effort to shed light on how microfluidics can facilitate the use of zebrafish as a gene screening tool. Zebrafish is ranked the third most important animal model after rats and mice, according to a National Institutes of Health (NIH) announcement in 2003. It has become a staple for scientists to examine and subsequently begin to unravel the mystery of human diseases, and is increasingly used in toxicological studies for new drug development. The unique characteristics that this tiny fish possesses, including rapid growth rate, prodigious numbers of offspring, and eggs that develop outside the body, make it an invaluable genetic tool. Evidently, these advantages can be broadened with the addition of a properly designed microfluidic circuit. By means of the presented illustrations and demonstrated applications, the goal is to spark interest in the development of more novel microfluidic platform designs that can leverage the attributes of zebrafish and quickly come to commercial fruition.
25th Anniversary Article: Charge Transport and Recombination in Polymer Light‐Emitting Diodes
Authors: Kuik Martijn , Wetzelaer Gert‐Jan A. H. , Nicolai Herman T. , Craciun N. Irina , De Leeuw Dago M. , Blom Paul W. M.
Published: January 2014

This article reviews the basic physical processes of charge transport and recombination in organic semiconductors. As a workhorse, LEDs based on a single layer of poly(p‐phenylene vinylene) (PPV) derivatives are used. The hole transport in these PPV derivatives is governed by trap‐free space‐charge‐limited conduction, with the mobility depending on the electric field and charge‐carrier density. These dependencies are generally described in the framework of hopping transport in a Gaussian density of states distribution. The electron transport on the other hand is orders of magnitude lower than the hole transport. The reason is that electron transport is hindered by the presence of a universal electron trap, located at 3.6 eV below vacuum with a typical density of ca. 3 × 1017 cm−3. The trapped electrons recombine with free holes via a non‐radiative trap‐assisted recombination process, which is a competing loss process with respect to the emissive bimolecular Langevin recombination. The trap‐assisted recombination in disordered organic semiconductors is governed by the diffusion of the free carrier (hole) towards the trapped carrier (electron), similar to the Langevin recombination of free carriers where both carriers are mobile. As a result, with the charge‐carrier mobilities and amount of trapping centers known from charge‐transport measurements, the radiative recombination as well as loss processes in disordered organic semiconductors can be fully predicted. Evidently, future work should focus on the identification and removing of electron traps. This will not only eliminate the non‐radiative trap‐assisted recombination, but, in addition, will shift the recombination zone towards the center of the device, leading to an efficiency improvement of more than a factor of two in single‐layer polymer LEDs.
Foam electrospinning: A multiple jet, needle‐less process for nanofiber production
Authors: Higham Alina K. , Tang Christina , Landry Alexandra M. , Pridgeon Monty C. , Lee Esther M. , Andrady Anthony L. , Khan Saad A.
Published: January 2014

A multiple jet, needle‐less process to fabricate electrospun nanofibers from foamed columns, produced by injecting compressed gas through a porous surface into polymer solutions, capable of circumventing syringe electrospinning shortcomings such as needle clogging and restrictions in production rate is presented. Using polyvinyl alcohol and polyethylene oxide (PEO) as model systems, we identify key design, processing, and solution parameters for producing uniform fibers. Increasing electrode surface area produces thicker mats, suggesting charge distribution through the bulk foam facilitates electrospinning. Similar trends between foam and syringe electrospinning are observed for collection distance, electric field strength, and polymer concentration. Interestingly, the empirical correlation between polymer entanglement and fiber formation are found to be similar for both foam and traditional needle electrospinning, but the fiber crystallinity shows enhancement with foam electrospinning. In addition, foam electrospinning with a PEO‐nonionic surfactant system yields two orders of magnitude increase in production rate compared to syringe electrospinning. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1355–1364, 2014
Myelodysplastic syndromes: 2014 update on diagnosis, risk‐stratification, and management
Authors: Garcia‐Manero Guillermo
Published: January 2014

Disease overview: The myelodysplastic (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older male and in individuals with prior exposure to cytotoxic therapy.

Diagnosis: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is complementary but not diagnostic.

Risk‐stratification: Prognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of blasts in the bone marrow and cytogenetic characteristics. The most commonly used system is the International Prognostic Scoring System (IPSS). IPSS is likely to be replaced by a new revised score (IPSS‐R) and by the incorporation of new molecular markers recently described.

Risk‐adapted therapy: Therapy is selected based on risk, transfusion needs, percent of bone marrow blasts and more recently cytogenetic profile. Goals of therapy are different in lower risk patients than in higher risk. In lower risk, the goal is to decrease transfusion needs and transformation to higher risk disease or AML, as well as to improve survival. In higher risk, the goal is to prolong survival. Current available therapies include growth factor support, lenalidomide, hypomethylating agents, intensive chemotherapy, and allogeneic stem cell transplantation. The use of lenalidomide has significant clinical activity in patients with lower risk disease, anemia, and a chromosome 5 alteration. 5‐Azacitidine and decitabine have activity in higher risk MDS. 5‐Azacitidine has been shown to improve survival in higher risk MDS. A number of new molecular lesions have been described in MDS that may serve as new therapeutic targets or aid in the selection of currently available agents. Additional supportive care measures may include the use of prophylactic antibiotics and iron chelation.

Management of progressive or refractory disease: There are no approved interventions for patients with progressive or refractory disease particularly after hypomethylating based therapy. Options include cytarabine based therapy, transplantation and participation on a clinical trial. Am. J. Hematol. 89:98–108, 2014. © 2013 Wiley Periodicals, Inc.
Impact of comorbidities by ACE‐27 in the revised‐IPSS for patients with myelodysplastic syndromes
Authors: Daver Naval , Naqvi Kiran , Jabbour Elias , Kadia Tapan , DiNardo Courtney , Cardenas‐Turanzas Marylou , Pierce Sherry , Nguyen Khanh Thi‐Thuy , Bueso‐Ramos Carlos , Kantarjian Hagop , Garcia‐Manero Guillermo
Published: January 2014

Comorbidities significantly affect the prognosis and outcomes of patients with hematological malignancies. We have previously reported the impact of comorbidities on the International Prognostic Scoring System (IPSS) score. The aim of this study was to determine whether comorbidities continued to have a significant impact when patients were reclassified according to the Revised‐IPSS (IPSS‐R). The medical records of 600 consecutive myelodysplastic syndrome patients who presented to MD Anderson Cancer Center between January 2002 and June 2004 were reviewed. The Adult Comorbidity Evaluation‐27 (ACE‐27) was used to assess the severity of comorbid conditions. Four hundred and two (67%) patients were male. Median age at presentation was 66.6 years (17–94). Mean duration of follow‐up was 54 months (1–100). Five hundred and two (84%) patients died, and 54 (9%) patients underwent stem cell transplantation. Overall median survival was 16.8 months (1–100). Median survival by IPSS‐R was 47, 34, 21, 16, and 6 months for patients in very low, low, intermediate, high, and very high‐risk groups, respectively (P < 0.001). The ACE‐27 comorbidity score significantly impacted the median survival of patients in the intermediate (P < 0.001), high (P = 0.045), and very high (P = 0.004) IPSS‐R groups; but did not significantly impact the median survival in the low (P = 0.11) and very low (P = 0.49) IPSS‐R groups. The ACE‐27 comorbidity score significantly impacted the median survival of patients ≤65 years (P < 0.001) but did not significantly impact those >65 years (P = 0.18). Assessment of comorbidity may enhance the prognostic ability of the IPSS‐R. Am. J. Hematol. 89:509–516, 2014. © 2014 Wiley Periodicals, Inc.
JAK2V617F monitoring in polycythemia vera and essential thrombocythemia: Clinical usefulness for predicting myelofibrotic transformation and thrombotic events
Authors: Alvarez‐Larrán Alberto , Bellosillo Beatriz , Pereira Arturo , Kerguelen Ana , Carlos Hernández‐Boluda Juan , Martínez‐Avilés Luz , Fernández‐Rodríguez Concepción , Gómez Montse , Lombardía Luis , Angona Anna , Ancochea Águeda , Senín Alicia , Longarón Raquel , Navarro Blanca , Collado María , Besses Carlos
Published: January 2014

The JAK2V617F allele burden has been identified as a risk factor for vascular events and myelofibrotic transformation in polycythemia vera (PV) and essential thrombocythemia (ET). However, all previous studies have evaluated a single time point JAK2V617F measurement. Therefore, the frequency and the clinical significance of changes in the JAK2V617F mutant load occurring during the disease evolution remain unknown. In the present study, JAK2V617F monitoring was performed during the follow‐up of 347 patients (PV = 163, ET = 184). According to their JAK2V617F evolutionary patterns, patients were stratified as stable < 50% (n = 261), stable ≥50% (n = 52), progressive increase (n = 24) and unexplained decrease (n = 10). After a 2,453 person‐years follow‐up, a total of 59 thrombotic events, 16 major hemorrhages, and 27 cases of myelofibrotic transformations were registered. At multivariate analyses, patients with a persistently high (≥50%) or unsteady JAK2V617F load during follow‐up had an increased risk of myelofibrotic transformation (Incidence rate ratio [IRR]: 20.7, 95% CI: 6.5–65.4; P < 0.001) and a trend for a higher incidence of thrombosis (IRR: 1.7, 1–3.3; P = 0.05) than patients with a stable allele burden below 50%. In conclusion, JAK2V617F monitoring could be useful in patients with PV and ET for predicting disease's complications, especially myelofibrotic transformation. Am. J. Hematol. 89:517–523, 2014. © 2014 Wiley Periodicals, Inc.
Coronary artery disease and cancer mortality in a cohort of workers exposed to vinyl chloride, carbon disulfide, rotating shift work, and o‐toluidine at a chemical manufacturing plant
Authors: Carreón Tania , Hein Misty J. , Hanley Kevin W. , Viet Susan M. , Ruder Avima M.
Published: January 2014

Background

We updated through 2007 the mortality experience of 1,874 workers employed at a New York State chemical manufacturing plant between 1946 and 2006.

Methods

Reassessed exposures to vinyl chloride, carbon disulfide, and shift work and categories of o‐toluidine exposure were based on year, department and job title. Standardized mortality ratios (SMR) compared mortality to that of the US population. Internal comparisons used directly standardized rate ratios.

Results

Hepatobiliary cancer mortality was elevated among workers ever exposed to vinyl chloride (SMR = 3.80, 95% confidence interval 1.89–6.80); directly standardized rates increased with increasing vinyl chloride exposure duration. No increase in non‐Hodgkin lymphoma mortality was observed with vinyl chloride and shift work exposures. Internal comparisons showed increased coronary artery disease mortality among long‐term workers exposed to carbon disulfide and shift work for 4 years or more.

Conclusions

Excess coronary artery disease mortality confirms earlier results; further investigation is needed to understand risk factors. Am. J. Ind. Med. 57:398–411, 2014. © 2014 Wiley Periodicals, Inc.
Contingent workers: Workers' compensation data analysis strategies and limitations
Authors: Foley Michael , Ruser John , Shor Glenn , Shuford Harry , Sygnatur Eric
Published: January 2014

The growth of the contingent workforce presents many challenges in the occupational safety and health arena. State and federal laws impose obligations and rights on employees and employers, but contingent work raises issues regarding responsibilities to maintain a safe workplace and difficulties in collecting and reporting data on injuries and illnesses.

Contingent work may involve uncertainty about the length of employment, control over the labor process, degree of regulatory, or statutory protections, and access to benefits under workers' compensation.

The paper highlights differences in regulatory protections and benefits among various types of contingent workers and how these different arrangements affect safety incentives. It discusses challenges caused by contingent work for accurate data reporting in existing injury and illness surveillance and benefit programs, differences between categories of contingent work in their coverage in various data sources, and opportunities for overcoming obstacles to effectively using workers' compensation data. Am. J. Ind. Med. 57:764–775, 2014. © 2014 Wiley Periodicals, Inc.
Technical Note: Cervical dimensions for in situ and loose teeth: A critique of the Hillson et al. (2005) method
Authors: Aubry Bryan Scott
Published: January 2014

In 2005, Hillson and colleagues developed a method for obtaining cervicometrics on a collection of loose teeth. However, I identified problems with the method when trying to apply it to material from archaeological collections with a mixture of in situ and loose teeth. The correct placement of the caliper tips at the suggested mesiodistal landmarks proved impossible for many in situ teeth. Their recommendation to rotate teeth to access the suggested landmarks resulted in large errors because not all teeth could be rotated. Other problems were identified with the suggested buccolingual dimensions of molars, which produced measurements that are not homologous across tooth class because of differential reduction in the distal cusps. Am J Phys Anthropol 154:159–164, 2014. © 2014 Wiley Periodicals, Inc.
Von Disilen (SiSi) über Phosphasilen (SiP) zum Phosphakumulen (PCN)
Authors: Willmes Philipp , Cowley Michael J. , Hartmann Marco , Zimmer Michael , Huch Volker , Scheschkewitz David
Published: January 2014

Die Erzeugung schwerer Doppelbindungssysteme ohne Bildung von Koppel‐ oder Nebenprodukten ist von großer Bedeutung für deren Anwendung in der Synthese. Periphere funktionelle Gruppen sind in dieser Hinsicht wegen der ihnen eigenen Mobilität vielversprechend. In Anhängigkeit vom sterischen Anspruch des N‐Alkylsubstituenten R ergibt die Reaktion des Disilenids Ar2SiSi(Ar)Li (Ar=2,4,6‐iPr3C6H2) mit Chlorphosphanen ClP(NR2)2 entweder das Phosphinodisilen Ar2SiSi(Ar)P(NR2)2 (für R=iPr) oder P‐aminofunktionalisierte Phosphasilene Ar2(R2N)SiSi(Ar)P(NR2) (für R=Et, Me) über 1,3‐Verschiebung einer der Aminogruppen. Im Fall von R=Me erfolgt nach Zugabe eines Äquivalents tert‐Butylisocyanid eine zweite Aminogruppenwanderung zum 1‐Aza‐3‐phosphaallen Ar2(R2N)SiSi(NR2)(Ar)PCNtBu mit ausgeprägtem Ylid‐Charakter. Alle neuen Verbindungen wurden durch Multikern‐NMR‐Spektroskopie vollständig charakterisiert, zusätzlich in ausgewählten Fällen durch Einkristall‐Röntgenbeugung und DFT‐Rechnungen.
Real‐Time Monitoring of New Delhi Metallo‐β‐Lactamase Activity in Living Bacterial Cells by 1H NMR Spectroscopy
Authors: Ma Junhe , McLeod Sarah , MacCormack Kathleen , Sriram Shubha , Gao Ning , Breeze Alexander L. , Hu Jun
Published: January 2014

Disconnections between in vitro responses and those observed in whole cells confound many attempts to design drugs in areas of serious medical need. A method based on 1D 1H NMR spectroscopy is reported that affords the ability to monitor the hydrolytic decomposition of the carbapenem antibiotic meropenem inside Escherichia coli cells expressing New Delhi metallo‐β‐lactamase subclass 1 (NDM‐1), an emerging antibiotic‐resistance threat. Cell‐based NMR studies demonstrated that two known NDM‐1 inhibitors, L‐captopril and ethylenediaminetetraacetic acid (EDTA), inhibit the hydrolysis of meropenem in vivo. NDM‐1 activity in cells was also shown to be inhibited by spermine, a porin inhibitor, although in an in vitro assay, the influence of spermine on the activity of isolated NDM‐1 protein is minimal. This new approach may have generic utility for monitoring reactions involving diffusible metabolites in other complex biological matrices and whole‐cell settings, including mammalian cells.
Arrays of polyacrylamide hydrogels using a carbodiimide‐mediated crosslinking reaction
Authors: Sheng Qi , Tian Wendy , Lapierre Florian , Gao Song , Mulder Roger J. , Zhu Yonggang , Kozielski Karen A. , Wood Colin D.
Published: January 2014

This study introduces a radical‐free approach for generating polyacrylamide (PAM) hydrogels with no toxic residues remaining in the networks. Acrylamide and bisacrylamide, which are neurotoxins, are not used during the hydrogel synthesis and only nontoxic side products are generated. This is achieved using a gentle carbodiimide‐mediated crosslinking (CMCL) reaction that does not require complex initiation systems and is effective in the presence of oxygen. This overcomes some of the key limitations related to PAM hydrogel synthesis using free‐radical routes and maintains the advantages of synthetic hydrogels over biopolymers. In addition, the CMCL reaction allows for accurate placement of functional groups, which controls hydrogel structure and performance including mechanical strength, swelling capacity, and hydrophobic balance. This flexibility is demonstrated through the synthesis and rheological characterization of a library of structurally diverse hydrogels as well as spherical hydrogels. PAM‐based hydrogels are used extensively in a broad number of applications, and this study demonstrates the applicability of this method as a nontoxic and radical‐free complementary alternative route that can generate structures analogous to those prepared using free‐radical routes. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40416.
Exploring the mechanism how Marburg virus VP35 recognizes and binds dsRNA by molecular dynamics simulations and free energy calculations
Authors: Xue Qiao , Zheng Qing‐Chuan , Zhang Ji‐Long , Cui Ying‐Lu , Zhang Hong‐Xing
Published: January 2014

Filoviruses often cause terrible infectious disease which has not been successfully dealt with pharmacologically. All filoviruses encode a unique protein termed VP35 which can mask doubled‐stranded RNA to deactivate interferon. The interface of VP35–dsRNA would be a feasible target for structure‐based antiviral agent design. To explore the essence of VP35–dsRNA interaction, molecular dynamics simulation combined with MM‐GBSA calculations were performed on Marburg virus VP35–dsRNA complex and several mutational complexes. The energetic analysis indicates that nonpolar interactions provide the main driving force for the binding process. Although the intermolecular electrostatic interactions play important roles in VP35–dsRNA interaction, the whole polar interactions are unfavorable for binding which result in a low binding affinity. Compared with wild type VP35, the studied mutants F228A, R271A, and K298A have obviously reduced binding free energies with dsRNA reflecting in the reduction of polar or nonpolar interactions. The results also indicate that the loss of binding affinity for one dsRNA strand would abolish the total binding affinity. Three important residues Arg271, Arg294, and Lys298 which makes the largest contribution for binding in VP35 lose their binding affinity significantly in mutants. The uncovering of VP35–dsRNA recognition mechanism will provide some insights for development of antiviral drug. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 849–860, 2014.
Determination of mazindol in human oral fluid by high performance liquid chromatography–electrospray ionization mass spectrometry
Authors: de Oliveira Marcella Herbstrith , Carlos Graciela , Bergold Ana Maria , Pechansky Flavio , Limberger Renata Pereira , Fröehlich Pedro Eduardo
Published: January 2014

Brazil is one of the countries most affected by abuse of stimulant medications by professional drivers, especially fenproporex, amfepramone and mazindol. Even though their sale is banned, they can be found in illegal markets, such as those located on the country's borders. The use of oral fluid to monitor drug levels has many advantages over plasma and urine because it is noninvasive, easier to collect and more difficult to adulterate. The aim of this study was to develop and validate a sensitive and specific method to quantify mazindol in human oral fluid by liquid chromatography–mass spectrometry (LC‐MS). The LC system consisted of an LC‐MS system operated in selected ion monitoring mode. The mobile phase was composed of water at pH 4.0, acetonitrile and methanol (60:15:25 v/v/v) at a flow rate of 1.0 mL/min and propranolol was used as internal standard. Total running time was 10 min. The lower limit of quantification was 0.2 ng/mL and the method exhibited good linearity within the 0.2–20 ng/mL range (r = 0.9987). A rapid, specific, sensitive, linear, precise and accurate method was developed for determination of mazindol in human oral fluid according to European Medicines Agency guidelines, and is suitable for monitoring mazindol levels in oral fluid of professional drivers. Copyright © 2014 John Wiley & Sons, Ltd.
Through Thick and Thin? How Self‐determination Drives the Corporate Sustainability Initiatives of Multinational Subsidiaries
Authors: Shah Kalim U. , Arjoon Surendra
Published: January 2014

Multinational corporation (MNC) subsidiaries implement corporate sustainability initiatives (CSIs) if they are self‐determined to do so (based on intrinsic motivation) or when urged on by circumstances and pressures (based on extrinsic motivation). Such differences in self‐determination are derived from underlying corporate psychological needs for competence, autonomy and relatedness, and are manifested in the governance choices of making, allying or buying CSIs. In this study of oil and gas MNC subsidiaries in the developing country context of Trinidad and Tobago, four distinct types of firm are identified based on their levels of self‐determination and corporate governance tendencies. These groups are identified as trail blazers, marching soldiers, sharp shooters and fire fighters, and their distinctive characteristics are described. These findings are useful to corporate sustainability strategists seeking to select, design and implement CSIs that satisfy MNC headquarter directives but balance subsidiary objectives of maintaining good relations and access to operate in developing countries. Copyright © 2014 John Wiley & Sons, Ltd and ERP Environment
Brand preference affects the threshold for perceptual awareness
Authors: Ramsøy Thomas Zoëga , Skov Martin
Published: January 2014

Despite decades of scientific scrutiny, much is still unknown about the effects that brands have on perception. Brands are known to lead to changes in attention and mnemonic processing and by altering emotional preferences they imbue products with value. Less, however, is known about the exact mechanism through which this occurs. Here, a novel and unexpected finding is provided in which subjective brand preference alters the likelihood that a brand name will be consciously seen. By presenting brand names at brief durations, and having them respond using a graded evaluation of conscious perception, the Perception Awareness Scale, it is found that brand names for which there is either a positive and negative preference, subjects report seeing the name more clearly. Interestingly, and much to the contrary of studies of basic emotions, this effect is strongest for positive preference. Our results are discussed in light of other studies in consumer psychology and consciousness science. Copyright © 2013 John Wiley & Sons, Ltd.
3‐Substituted Indazoles as Configurationally Locked 4EGI‐1 Mimetics and Inhibitors of the eIF4E/eIF4G Interaction
Authors: Yefidoff‐Freedman Revital , Chen Ting , Sahoo Rupam , Chen Limo , Wagner Gerhard , Halperin Jose A. , Aktas Bertal H. , Chorev Michael
Published: January 2014

4EGI‐1, the prototypic inhibitor of eIF4E/eIF4G interaction, was identified in a high‐throughput screening of small‐molecule libraries with the aid of a fluorescence polarization assay that measures inhibition of binding of an eIF4G‐derived peptide to recombinant eIF4E. As such, the molecular probe 4EGI‐1 has potential for the study of molecular mechanisms involved in human disorders characterized by loss of physiological restraints on translation initiation. A hit‐to‐lead optimization campaign was carried out to overcome the configurational instability in 4EGI‐1, which stems from the E‐to‐Z isomerization of the hydrazone function. We identified compound 1 a, in which the labile hydrazone was incorporated into a rigid indazole scaffold, as a promising rigidified 4EGI‐1 mimetic lead. In a structure–activity relationship study directed towards probing the structural latitude of this new chemotype as an inhibitor of eIF4E/eIF4G interaction and translation initiation we identified 1 d, an indazole‐based 4EGI‐1 mimetic, as a new and improved lead inhibitor of eIF4E/eIF4G interaction and a promising molecular probe candidate for elucidation of the role of cap‐dependent translation initiation in a host of pathophysiological states.
A Deadly Organometallic Luminescent Probe: Anticancer Activity of a ReI Bisquinoline Complex
Authors: Kitanovic Igor , Can Suzan , Alborzinia Hamed , Kitanovic Ana , Pierroz Vanessa , Leonidova Anna , Pinto Antonio , Spingler Bernhard , Ferrari Stefano , Molteni Roberto , Steffen Andreas , Metzler‐Nolte Nils , Wölfl Stefan , Gasser Gilles
Published: January 2014

The photophysical properties of [Re(CO)3(L‐N3)]Br (L‐N3=2‐azido‐N,N‐bis[(quinolin‐2‐yl)methyl]ethanamine), which could not be localized in cancer cells by fluorescence microscopy, have been revisited in order to evaluate its use as a luminescent probe in a biological environment. The ReI complex displays concentration‐dependent residual fluorescence besides the expected phosphorescence, and the nature of the emitting excited states have been evaluated by DFT and time‐dependent (TD) DFT methods. The results show that fluorescence occurs from a 1LC/MLCT state, whereas phosphorescence mainly stems from a 3LC state, in contrast to previous assignments. We found that our luminescent probe, [Re(CO)3(L‐N3)]Br, exhibits an interesting cytotoxic activity in the low micromolar range in various cancer cell lines. Several biochemical assays were performed to unveil the cytotoxic mechanism of the organometallic ReI bisquinoline complex. [Re(CO)3(L‐N3)]Br was found to be stable in human plasma indicating that [Re(CO)3(L‐N3)]Br itself and not a decomposition product is responsible for the observed cytotoxicity. Addition of [Re(CO)3(L‐N3)]Br to MCF‐7 breast cancer cells grown on a biosensor chip micro‐bioreactor immediately led to reduced cellular respiration and increased glycolysis, indicating a large shift in cellular metabolism and inhibition of mitochondrial activity. Further analysis of respiration of isolated mitochondria clearly showed that mitochondrial respiratory activity was a direct target of [Re(CO)3(L‐N3)]Br and involved two modes of action, namely increased respiration at lower concentrations, potentially through increased proton transport through the inner mitochondrial membrane, and efficient blocking of respiration at higher concentrations. Thus, we believe that the direct targeting of mitochondria in cells by [Re(CO)3(L‐N3)]Br is responsible for the anticancer activity.
Neighboring Residue Effects in Terminally Blocked Dipeptides: Implications for Residual Secondary Structures in Intrinsically Unfolded/Disordered Proteins
Authors: Jung Young‐Sang , Oh Kwang‐Im , Hwang Geum‐Sook , Cho Minhaeng
Published: January 2014

For nuclear magnetic resonance (NMR)‐based protein structure determinations, the random coil chemical shifts are very important because the secondary and tertiary protein structure predictions become possible by examining deviations of measured chemical shifts from those reference chemical shift values. In addition, neighboring residue effects on chemical shifts and J‐coupling constants are crucial in understanding the nature of conformational propensities exhibited by unfolded or intrinsically disordered proteins. We recently reported the 1D NMR results for a complete set of terminally blocked dipeptides (Oh KI, Jung YS, Hwang GS, Cho M. J Biomol NMR 2012;53:25–41), but the NMR resonance assignments were not possible so that the average chemical shifts and J‐coupling constants were only considered. In the present work, to thoroughly investigate the neighboring residue effects and random coil chemical shifts we extend the previous studies with 2D NMR, and measured all the 3JHNHα values and Hα and HN chemical shifts of the same set of terminally blocked dipeptides that are free from structural effects like secondary structure, hydrogen‐bond, long‐range backbone, and side‐chain interactions. In particular, the preceding and following residue effects on amino‐acid backbone conformational propensities are revealed and directly compared with previous works on either short peptides or empirical chemical shift database. Chirality 26:443‐452, 2014. © 2014 Wiley Periodicals, Inc.
The Catalytic Pathways of Hydrohalogenation over Metal‐Free Nitrogen‐Doped Carbon Nanotubes
Authors: Zhou Kai , Li Bo , Zhang Qiang , Huang Jia‐Qi , Tian Gui‐Li , Jia Jin‐Chao , Zhao Meng‐Qiang , Luo Guo‐Hua , Su Dang Sheng , Wei Fei
Published: January 2014

Nitrogen‐doped carbon nanotubes (N‐CNTs) are found to be active as one novel heterogeneous catalyst for acetylene hydrochlorination reaction, possessing good activity (TOF=2.3×10−3 s−1) and high selectivity (>98 %). Compared to toxic and energy‐consuming conventional catalysts, such as HgCl2, N‐CNTs are more favorable in terms of sustainability, because of their thermo‐stability, metal‐free make up, and the wide availability of bulk CNT. Coupling X‐ray photoelectron spectroscopy and density functional theory computations (DFT), the main active source and reaction pathway are shown. Good linearity between the quaternary nitrogen content and conversion is revealed. DFT study shows that the nitrogen doping enhanced the formation of the covalent bond between C2H2 and NCNT compared with the undoped CNT, and therefore promoted the addition reaction of the C2H2 and HCl into C2H3Cl.
Concomitant evaluation of PMA+ionomycin‐induced kinase phosphorylation and cytokine production in T cell subsets by flow cytometry
Authors: Crawford Timothy Q. , Jalbert Emilie , Ndhlovu Lishomwa C. , Barbour Jason D.
Published: January 2014

Methods to detect intracellular kinase signaling intermediates by flow cytometry have been recently developed. Termed “phospho‐flow,” these methods employ fluorescence‐conjugated monoclonal antibodies that recognize phosphorylated epitopes of intracellular kinases, and may be combined with surface phenotypic markers to observe changes in kinase pathways by cellular subset. Effector functions, like cytokine production, are processes intrinsically linked to intracellular signaling and kinase activity within each cell. Methodologies that would simultaneously detect changes to signaling pathways as well as effector responses at the single‐cell level would allow for mapping of the functional consequences induced by signaling pathway modifications. However, there are challenges to developing such a combined protocol, relating to the different kinetics of rapid signaling events and the more prolonged time required to induce and observe cytokine responses. In this report, we describe the development of an assay that accommodates differences in protocol conditions and response kinetics, merging phospho‐flow cytometry, and intracellular cytokine staining methods into a single experimental protocol. We examined intracellular ERK1/2 phosphorylation and IFN‐γ production by CD4+ and CD8+ T cells upon polyclonal stimulation with PMA and ionomycin, while monitoring expression of the cytolytic molecule perforin and the T cell activation marker CD38. We present a method that allows observation of kinase phosphorylation and cytokine production within the same cell after stimuli, while maintaining a stable cellular phenotype. Monitoring of signaling and effector functions in distinct immune subsets provides a platform to investigate and relate intracellular kinase signaling activity to immune cell effector function and phenotype in disease states. © 2014 International Society for Advancement of Cytometry
Do you “like” my photo? Facebook use maintains eating disorder risk
Authors: Mabe Annalise G. , Forney K. Jean , Keel Pamela K.
Published: January 2014

Objective

Social media sites, such as Facebook, merge two factors that influence risk for eating disorders: media and peers. Previous work has identified cross‐sectional and temporal associations between Facebook use and disordered eating. This study sought to replicate and extend these findings using an experimental design.

Method

In Study 1, 960 women completed self‐report surveys regarding Facebook use and disordered eating. In Study 2, 84 women were randomly assigned to use Facebook or to use an alternate internet site for 20 min.

Results

More frequent Facebook use was associated with greater disordered eating in a cross‐sectional survey. Facebook use was associated with the maintenance of weight/shape concerns and state anxiety compared to an alternate internet activity.

Discussion

Facebook use may contribute to disordered eating by maintaining risk for eating pathology. As such, targeting Facebook use may be helpful in intervention and prevention programs. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:516–523)
Increased plasma level of soluble urokinase plasminogen activator receptor is associated with incidence of heart failure but not atrial fibrillation
Authors: Borné Yan , Persson Margaretha , Melander Olle , Smith J. Gustav , Engström Gunnar
Published: January 2014

Aims

Soluble urokinase plasminogen activator receptor (suPAR) in plasma is a novel inflammatory marker thought to be released from the cell surface of neutrophils, T cells, and macrophages. Other inflammatory markers, mainly acute phase proteins produced in the liver, have been associated with the incidence of heart failure (HF) and atrial fibrillation (AF). We investigated the association between suPAR and incident HF and AF in a population‐based cohort.

Methods and results

Soluble urokinase plasminogen activator receptor was measured in 4530 subjects (aged 46–68 years, 61% women), who participated in the Malmö Diet and Cancer study during 1991–1996. Incident cases of HF and AF were identified from the Swedish hospital discharge register during a median follow‐up of 16.3 years. During follow‐up, 109 subjects (55% men) were diagnosed with new‐onset HF and 321 individuals (50% men) with AF. suPAR was significantly associated with increased plasma levels of NT‐proBNP (P < 0.001). suPAR was significantly associated with incidence of HF [hazard ratio (HR) for the third vs. first tertile 3.33, 95% confidence interval (CI) 1.91–5.81 after adjustment for age and sex; and HR 1.82, 95% CI 1.02–3.27, P for trend 0.018 after adjustment for conventional risk factors and biomarkers]. suPAR was significantly associated with incidence of AF, when adjusted for age and sex (HR 1.40, 95% CI 1.06–1.85). However, this relationship was non‐significant after adjustment for conventional risk factors and biomarkers.

Conclusion

Soluble urokinase plasminogen activator receptor was associated with increased plasma levels of NT‐proBNP and incidence of HF, but not with AF among middle‐aged subjects.
Hybrid phospholipid bilayer coatings for separations of cationic proteins in capillary zone electrophoresis
Authors: Gallagher Elyssia S. , Adem Seid M. , Bright Leonard K. , Calderon Isen A. C. , Mansfield Elisabeth , Aspinwall Craig A.
Published: January 2014

Protein separations in CZE suffer from nonspecific adsorption of analytes to the capillary surface. Semipermanent phospholipid bilayers have been used to minimize adsorption, but must be regenerated regularly to ensure reproducibility. We investigated the formation, characterization, and use of hybrid phospholipid bilayers (HPBs) as more stable biosurfactant capillary coatings for CZE protein separations. HPBs are formed by covalently modifying a support with a hydrophobic monolayer onto which a self‐assembled lipid monolayer is deposited. Monolayers prepared in capillaries using 3‐cyanopropyldimethylchlorosilane (CPDCS) or n‐octyldimethylchlorosilane (ODCS) yielded hydrophobic surfaces with lowered surface free energies of 6.0 ± 0.3 or 0.2 ± 0.1 mJ m−2, respectively, compared to 17 ± 1 mJ m−2 for bare silica capillaries. HPBs were formed by subsequently fusing vesicles comprised of 1,2‐dilauroyl‐sn‐glycero‐3‐phosphocholine or 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine to CPDCS‐ or ODCS‐modified capillaries. The resultant HPB coatings shielded the capillary surface and yielded reduced electroosmotic mobility (1.3–1.9 × 10−4 cm2 V−1s−1) compared to CPDCS‐ and ODCS‐modified or bare capillaries (3.6 ± 0.2 × 10−4 cm2 V−1s−1, 4.8 ± 0.4 × 10−4 cm2 V−1s−1, and 6.0 ± 0.2 × 10−4 cm2 V−1s−1, respectively), with increased stability compared to phospholipid bilayer coatings. HPB‐coated capillaries yielded reproducible protein migration times (RSD ≤ 3.6%, n ≥ 6) with separation efficiencies as high as 200 000 plates/m.
Factors controlling transport of graphene oxide nanoparticles in saturated sand columns
Authors: Qi Zhichong , Zhang Lunliang , Wang Fang , Hou Lei , Chen Wei
Published: January 2014

The authors conducted column experiments and a modeling study to understand the effects of several environmental factors on the aggregation and transport of graphene oxide nanoparticles (GONPs) in saturated quartz sand. The GONPs were negatively charged and stable under the test conditions (0–50 mM NaCl; pH 4.8–9.0), and the Derjaguin–Landau–Verwey–Overbeek (DLVO) calculation indicated that deposition of GONPs was under unfavorable attachment conditions. The GONPs exhibited high mobility even at an ionic strength of 25 mM NaCl. The transport of GONPs was insensitive to the changes of pH (from 5.1 to 9.0), but the presence of 10 mg/L Suwannee River humic acid (SRHA) considerably enhanced transport at high ionic strength (35 mM NaCl), likely via enhanced steric repulsion and significantly inhibited stacking of GO flakes. Varying flow velocity also enhanced transport at high ionic strength. In general, GONPs exhibit greater mobility compared with other carbon nanoparticles because the aggregation and transport of GONPs are more resilient to changes in solution chemistry and hydrodynamic forces that favor aggregation and deposition of nanoparticles. A 2-site transport model incorporating both the blocking-affected attachment process and straining effects can effectively model the transport of GONPs. The high mobility of GONPs should be given full consideration in assessing their environmental risks. Environ Toxicol Chem 2014;33:998–1004. © 2014 SETAC
Risks related to car fire on innovative Poroelastic Road Surfaces—PERS
Authors: Świeczko‐Żurek Beata , Ejsmont Jerzy , Motrycz Grzegorz , Stryjek Piotr
Published: January 2014

To reduce tyre/road noise, the concept of poroelastic road surfaces (PERS) was invented. PERS is a road surface material that is porous, and at the same time, it is flexible because of the substantial amount of rubber granulate content (from 20% to 85%). The rubber and stone particles are bound by polyurethane resin instead of bitumen. It was feared that in case of fire, because of the high content of rubber and polyurethane, there may be considerable emission of potentially hazardous substances (such as hydrogen cyanide) from burning PERS. Tests performed by the Technical University of Gdansk show that the emission of toxic gases is rather small and that the surface does not promote car fire, even when soaked with fuel. Car fire with fuel spill on PERS is less dangerous for passengers than car fire on dense road surface as the fire is spreading much slower. The article presents results of laboratory and road experiments carried out within FP7 ‘PERSUADE’. Copyright © 2014 John Wiley & Sons, Ltd.