bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering cumulative fault slip vectors from fold scarps: Relationships between long‐term and coseismic deformations in central Western Taiwan
Authors: Le Béon Maryline , Suppe John , Jaiswal Manoj K. , Chen Yue‐Gau , Ustaszewski Michaela E.
Published: June 2014

We document the 30 ka cumulative slip history and long‐term slip vector azimuth on the northern Chelungpu fault based on a series of fault‐bend folded alluvial terraces and draw quantitative relationships between geological structure, deformation observed from the geomorphology, and coseismic displacements during the 1999Mw = 7.6 Chi‐Chi earthquake. In our study area, three main terrace levels show progressive folding by kink band migration in relation to the underlying fault geometry, forming a main N‐S fold scarp up to ~193 m high and secondary E‐W scarps. Detailed analysis using 5 m resolution digital elevation model allows us to characterize the scarp morphology and quantify the deformation parameters, namely, terrace heights, fold scarp relief, and fold limb width and slope angle. The 3‐D deformation of the highest terrace, dated by optically stimulated luminescence at 30.2 ± 4.0 ka, enables to simultaneously determine amplitude and azimuth of the long‐term slip vector based on scarp relief. The long‐term slip vector, oriented N338° ± 6°, is found to parallel the Chi‐Chi coseismic displacements in this area. Cumulative slip and dating results yield a constant slip rate of 17.7 ± 2.2 mm/a in the direction N338° ± 6°. Late Quaternary shortening rates observed at four sites vary along strike in a similar way to Chi‐Chi coseismic displacements. Together with the collinearity of long‐term and coseismic slip vectors at our study site, this suggests that Chi‐Chi earthquake is a characteristic earthquake for the Chelungpu thrust with recurrence interval ~470 years. We also discuss implications for the regional and long‐term distribution of shortening in the central Western Foothills.
Congress Examines Efforts to Search for Life in the Universe
Authors: Showstack Randy
Published: June 2014

“It is not hyperbolic to suggest that scientists could very well discover extraterrestrial intelligence within 2 decades' time or less, given resources to conduct the search,” Seth Shostak, senior astronomer with the SETI Institute, in Mountain View, Calif., testified at a 21 May congressional hearing held by the House of Representatives' Committee on Science, Space, and Technology. He pointed to the progress in extrasolar planet discovery made possible by NASA's Kepler space telescope, the enormous number of potential planets in the Milky Way and other galaxies, the increasing power of digital electronics to find and sort out radio and other signals, and other work related to exoplanets and astrobiology. It was the committee's third hearing on astrobiology and the search for life in the universe in roughly 1 year.
Quasi‐biennial oscillation predictable on multiannual time scales
Authors: Balcerak Ernie
Published: June 2014

The quasi‐biennial oscillation (QBO), a quasi‐periodic oscillation of easterly and westerly winds in the tropical stratosphere that is known to affect winter surface weather in the midlatitudes, is predictable several years into the future, according to a new modeling study by Scaife et al.
Deep water paleo‐iceberg scouring on top of Hovgaard Ridge–Arctic Ocean
Authors: Arndt Jan Erik , Niessen Frank , Jokat Wilfried , Dorschel Boris
Published: June 2014

In multibeam echosounder and subbottom profiler data acquired during R/V Polarstern cruise ARK‐VII/3a from the Hovgaard Ridge (Fram Strait), we found evidence for very deep (>1200 m) iceberg scouring. Five elongated seafloor features have been detected that are interpreted to be iceberg scours. The scours are oriented in north‐south/south‐north direction and are about 15 m deep, 300 m wide, and 4 km long crossing the entire width of the ridge. They are attributed to multiple giant paleo‐icebergs that most probably left the Arctic Ocean southward through Fram Strait. The huge keel depths are indicative of ice sheets extending into the Arctic Ocean being at least 1200 m thick at the calving front during glacial maxima. The deep St. Anna Trough or grounded ice observed at the East Siberian Continental Margin are likely source regions of these icebergs that delivered freshwater to the Nordic Seas.
Exploring the efficacy of different electric field models in driving a model of the plasmasphere
Authors: Ridley A. J. , Dodger A. M. , Liemohn M. W.
Published: June 2014

The dynamics of the plasmasphere are strongly controlled by the inner magnetospheric electric field. In order to capture realistically the erosion of the nightside plasmapause and the formation of the drainage plume in a model of the plasmasphere, the electric field must be accurate. This study investigates how well five different electric field models drive the Dynamic Global Core Plasma Model during eight storm periods. The five electric field models are the Volland‐Stern analytic formula with Maynard‐Chen Kpdependence, two versions of the Weimer statistical models (96 and 05), and two versions of the Assimilative Mapping of Ionospheric Electrodynamics (AMIE) technique using magnetometer and DMSP satellite data. Manually extracted plasmapause locations from images taken by the EUV instrument on the Imager for Magnetopause‐to‐Aurora Global Exploration (IMAGE) satellite, as described by Goldstein et al. (2005), were compared to the simulation results throughout the main phase of the eight events. Three methods of calculating the plasmapause were employed to determine the best fit to EUV data, using the maximum gradient, a constant density contour (fit method), and the location in which the modeled density fell significantly below the specified saturation density for the given radial position (saturation method). It was found that the simulations driven by the Weimer (1996) model produced the best fit overall and that the fit and saturation methods worked best for matching the model results to the observations.
Impact of vertical mixing on sea surface pCO2 in temperate seasonally stratified shelf seas
Authors: Rippeth T. P. , Lincoln B. J. , Kennedy H. A. , Palmer M. R. , Sharples J. , Williams C. A. J.
Published: June 2014

A key parameter in determining the exchange of CO2 across the ocean‐atmosphere interface is the sea surface partial pressure of carbon dioxide (pCO2). Temperate seasonally stratified shelf seas represent a significant sink for atmospheric CO2. Here an analytical model is used to quantify the impact of vertical mixing across the seasonal thermocline on pCO2. The model includes the impacts of the resultant dissolved inorganic carbon, heat, salt, and alkalinity fluxes on the solubility of CO2 and the effect of the inorganic carbon sink created by the primary production fuelled by the flux of limiting nutrient. The results indicate that diapycnal mixing drives a modest but continuous change in pCO2 of order 1–10 µatm d−1. In quantifying the individual impacts of the fluxes of the different parameters, we find that the impact of the fluxes of DIC and nitrate fluxes dominate. In consequence, both the direction and magnitude of the change in pCO2 are strongly dependent on the C:N uptake ratio in primary production. While the smaller impacts of the heat and salt fluxes tend to compensate for each other at midshelf locations, the heat flux dominates close to the shelf break. The analysis highlights the importance of the accurate parameterization of the C:N uptake ratio, the surface‐mixed layer depth, and the TKE dissipation rate within the seasonal thermocline in models to be used to predict the air‐sea exchange of carbon dioxide in these regimes. The results implicate storms as key periods of pCO2 perturbation.
Manipulating Natural Product Biosynthetic Pathways via DNA Assembler
Authors: Shao Zengyi , Zhao Huimin
Published: June 2014

DNA assembler is an efficient synthetic biology method for constructing and manipulating biochemical pathways. The rapidly increasing number of sequenced genomes provides a rich source for discovery of gene clusters involved in synthesizing new natural products. However, both discovery and economical production are hampered by our limited knowledge in manipulating most organisms and the corresponding pathways. By taking advantage of yeast in vivo homologous recombination, DNA assembler synthesizes an entire expression vector containing the target biosynthetic pathway and the genetic elements needed for DNA maintenance and replication. Here we use the spectinabilin clusters originated from two hosts as examples to illustrate the guidelines of using DNA assembler for cluster characterization and silent cluster activation. Such strategies offer unprecedented versatility in cluster manipulation, bypass the traditional laborious strategies to elicit pathway expression, and provide a new platform for de novo cluster assembly and genome mining for discovering new natural products. Curr. Protoc. Chem. Biol. 6:65‐100 © 2014 by John Wiley & Sons, Inc.
Synthesis of Hydrogen‐Bond Surrogate α‐Helices as Inhibitors of Protein‐Protein Interactions
Authors: Miller Stephen E. , Thomson Paul F. , Arora Paramjit S.
Published: June 2014

The α‐helix is a prevalent secondary structure in proteins and is critical in mediating protein‐protein interactions (PPIs). Peptide mimetics that adopt stable helices have become powerful tools for the modulation of PPIs in vitro and in vivo. Hydrogen‐bond surrogate (HBS) α‐helices utilize a covalent bond in place of an N‐terminal i to i+4 hydrogen bond and have been used to target and disrupt PPIs that become dysregulated in disease states. These compounds have improved conformational stability and cellular uptake as compared to their linear peptide counterparts. The protocol presented here describes current methodology for the synthesis of HBS α‐helical mimetics. The solid‐phase synthesis of HBS helices involves solid‐phase peptide synthesis with three key steps involving incorporation of N‐allyl functionality within the backbone of the peptide, coupling of a secondary amine, and a ring‐closing metathesis step. Curr. Protoc. Chem. Biol. 6:101‐116 © 2014 by John Wiley & Sons, Inc.
Decentralized adaptive command following and disturbance rejection for subsystems with local full‐state feedback
Authors: Polston J. Daniel , Hoagg Jesse B.
Published: June 2014

We present a decentralized model reference adaptive control method, where each local controller uses full‐state feedback from the local subsystem. The controller is strictly decentralized, meaning that no information (including reference‐model trajectories) is shared between local controllers. This decentralized controller achieves stabilization, command following, and disturbance rejection provided that the reference‐model commands and the disturbances are sinusoidal with known spectrum. The controller is effective for multi‐input subsystems with arbitrarily large subsystem interconnections. Copyright © 2014 John Wiley & Sons, Ltd.
Brief Communication: Seasonality of diet composition is related to brain size in New World Monkeys
Authors: van Woerden Janneke T. , van Schaik Carel P. , Isler Karin
Published: June 2014

New World monkeys exhibit a more pronounced variability in encephalization than other primate taxa. In this comparative study, we tested two current hypotheses on brain size evolution, the Expensive Brain hypothesis and the Cognitive Buffer hypothesis, in a sample of 21 platyrrhine species. A high degree of habitat seasonality may impose an energetic constraint on brain size evolution if it leads to a high variation in caloric intake over time, as predicted by the Expensive Brain Hypothesis. However, simultaneously it may also provide the opportunity to reap the fitness benefits of increased cognitive abilities, which enable the exploitation of high‐quality food resources even during periods of scarcity, as predicted by the Cognitive Buffer hypothesis. By examining the effects of both habitat seasonality and the variation in monthly diet composition across species, we found support for both hypotheses, confirming previous results for catarrhine primates and lemurs. These findings are in accordance with an energetic and ecological view of brain size evolution. Am J Phys Anthropol 154:628–632, 2014. © 2014 Wiley Periodicals, Inc.
Thermal decomposition of energetic thermoplastic elastomers of poly(glycidyl nitrate)
Authors: Zhang Zaijuan , Wang Gang , Luo Nan , Huang Muhua , Jin Miaomiao , Luo Yunjun
Published: June 2014

Energetic thermoplastic elastomers (ETPEs) are futuristic binders for propellant/explosive formulations. Poly(glycidyl nitrate) (PGN)‐based ETPEs have excellent performance, including a high energy and high oxygen content. PGN‐based ETPEs were synthesized on PGN as a soft segment and hexamethylene diisocyanate extended 1,4‐butanediol as a hard segment by a prepolymerization method. The thermal behavior of the PGN‐based ETPEs was investigated by thermogravimetric analysis (TGA) and derivative thermogravimetry. A fitting strategy was adopted to study every stage of decomposition. The results show that the ETPEs had four main decomposition processes, and the peaks of each stage were at 212, 262, 322, and 414°C. The gas products were tested by TGA/Fourier transform infrared spectroscopy/mass spectrometry, and the main gas products of the samples were N2O, CH2O, C2H4O, and CO2. The previous results indicate the proposed mechanism of thermal decomposition. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2014,131, 40965.
Monodispersed composite particles prepared via emulsifier‐free emulsion polymerization using waterborne polyurethane as microreactors
Authors: Zhuge Wenna , Pan Mingwang , Chang Yanning , Yuan Jinfeng , Wang Xiaomei , Sun Caili , Zhang Guanglin
Published: June 2014

Monodispersed polystyrene particles in submicrometer size were intriguingly prepared through emulsifier‐free batch‐seeded emulsion polymerization using nonmonodispersed waterborne polyurethane (WBPU) beads as microreactors. Different feed ratios of styrene (St)/WBPU for the preparation of composite particles were investigated, and the size–growth course was experimentally followed. The morphology and dispersity of the particles were characterized by scanning electron microscopy together with dynamic laser scattering particle size analyzer. Their inside structure was further characterized by transmission electron microscopy with ultramicrotomy combined with X‐ray photoelectron spectroscopy for the composite particles' surface analysis. The probable grafting polymerization of St from WBPU was verified by Fourier transform infrared spectroscopy and nuclear magnetic resonance instrument. The obtained composite particles were again employed as the seeds in the emulsion copolymerization of methyl methacrylate. As a result, the formed multilayered composite particles with reverse core–shell structure were also monodispersed and spherical. The mechanism of the formation of the monodispersed particles was proposed. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40985.
Study on quaternary ammonium modified tentacle‐type cellulose beads and its adsorption for
Authors: Zhang Na , Zhou Cheng‐Xianyi , Xie Tong‐Hui , Zhang Yong‐Kui
Published: June 2014

A novel anion exchange resin based on cellulose has been prepared to adsorb
for the urgent demand of silver and the high toxicity of metal‐cyanide complexes. Quaternary ammonium groups were grafted onto cellulose beads as main active sites in tentacle‐type through a series of chemical reactions. The substitution degree of each reaction was determined to be about 0.854, 2.125, and 2.899 mmol g−1, respectively. The resin exhibited excellent spherical shape with microporous structure by the observation of optical microscopy and scanning electron microscope. Moreover, the adsorption experiments demonstrated the adsorption was fast in alkaline condition. Fitting the data into isotherm and kinetic models gave the conclusion that the adsorption behavior matched better with Langmuir model and pseudo‐second‐order kinetic in initial time followed pseudo‐first‐order kinetic model in later phase. The equilibrium adsorption capacity was determined to be 3.016 mmol g−1. With the advantages of high capacity, short equilibrium time, and alkaline resistance, the resin would be considered to a top‐priority adsorbent for the separation of
. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40987.
Optimization of amphiphobic structural surface thickness in relation to its functionality on stainless steel plates
Authors: Yuan Wei‐Li , Su Chi‐Jung , Lei Chien‐Ming , Mou Chun‐Yueh
Published: June 2014

Fluorine‐based amphiphobic coatings have been widely used in commercial textiles to provide water‐ and oil‐repelling abilities. However, few reports from the literature survey have discussed the surface structural effects of the coated substrate on amphiphobicity. In this research, various thickness amphiphobic coatings based on mixed epoxy, tetraethylorthosilicate, and a particular alkoxysilane with fluorinated side chains (F‐silane) were deposited on Grade 420 stainless steel plates. Film amphiphobicity is characterized by measuring the water and oil contact angles of the coating. Film morphology is examined using atomic force microscopy. The deposited films free of F‐silane are thinner than 150 nm. The films become thick at high F‐silane volume percentage with the surface cavities, ridges, and granules being masked out. On the addition of F‐silane, the water contact angle of the deposited films increases up to 105° and then reaches a plateau of ∼ 107° with increasing F‐silane. In contrast, the oil contact angle increases up to 60° at first and then slowly declines with the F‐silane concentration. The total drop of oil contact angle by ∼ 20° was attributed to the masking out of surface features on film thickening. This indicates that the surface oleophobicity depends on surface structures. Therefore, improving surface amphiphobicity correlates with creating more refined multiscale surface structures during the industrial manufacturing process of steel plate, prior to surface modification by F‐silane. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41003.
The effect of modifier contents of polyvinyl pyrrolidone on the enhanced dielectric and microwave absorbing properties of multiwalled carbon nanotubes
Authors: Zhang Aibo , Cao Xiufen , Tang Meng , zheng Yaping , Lu Zhengbin , Shen Yongtao
Published: June 2014

Polyvinyl pyrrolidone (PVP) polymers were used as non‐covalent modifiers to modify the surface of multi‐walled carbon nanotubes (MWNTs) by ultrasonic dispersion method. The transmission electron microscope results suggest that a layer of polymers is wrapped on the surface of MWNTs, and the thickness is about 2.5 nm. The addition of PVP helps to facilitate uniform distribution of MWNTs and increases the interfacial multipoles formed between PVP and MWNTs, which plays an important role in the regulation of the dielectric parameter and the enhancement of the microwave absorbing properties. The effects of PVP loadings and thickness of PVP/MWNTs hybrids on the dielectric parameter of MWNTs are investigated. The microwave absorbing properties are calculated from the dielectric constants. The results show that the maximum reflection loss is −26.27 dB at 7.8 GHz while the loading of PVP on MWNTs is 8.0 wt % with a thickness of 3.0 mm. These results suggest that the PVP contents and absorber thickness are important factors for the improvement of dielectric loss and microwave absorption properties of MWNTs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41007.
Synthesis, structure, and characterization of glyoxal‐urea‐formaldehyde cocondensed resins
Authors: Deng Shuduan , Pizzi Antonio , Du Guanben , Zhang Jizhi , Zhang Jun
Published: June 2014

To decrease the formaldehyde emission of urea‐formaldehyde (UF) bonded products at source, monomethylol urea (MMU) was chosen to react with glyoxal (G), a nonvolatile and nontoxic aldehyde, to prepare a novel glyoxal‐urea‐formaldehyde (GUF) cocondensed resin. The GUF resins were synthesized with different MMU/G molar ratios, and the basic properties were tested. The GUF resins were characterized by ultraviolet‐visible spectroscopy, Fourier transform infrared spectroscopy, carbon‐13 nuclear magnetic resonance spectroscopy and matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI‐TOF‐MS). The results show that the synthesized GUF resins remain stable for at least 10 days at ambient temperature. Conjugated structures, and large amounts of OH, NH, CN, and CO groups with different levels of substitution exist in the GUF resin. There are two repeating motives in the MALDI‐TOF‐MS spectrum of the GUF resin, one of 175 ±1 Da and a second one of 161 ± 1 Da. Moreover, the peaks due to the dehydration condensation reaction of MMU also appear in the spectra. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41009.
Study the factors affecting the performance of organic–inorganic hybrid coatings
Authors: Li Weili , Huang Dong , Xing XinYu , Tang Jijun , Xing Yujin , Li Xiujuan , Zhang Jide
Published: June 2014

In this article, a series of hybrid organic–inorganic coatings based on silica‐epoxy composite resins were prepared with the sol‐gel method by using γ‐aminopropyl triethoxysilane as a coupling agent. Especially, the research emphasized on the factors that influenced on the properties of the prepared hybrid coatings. Firstly, epoxy resin was reacted with γ‐aminopropyl triethoxysilane at a specific feeding molar ratio; subsequently, the asprepared sol–gel precursor was cohydrolyzed with tetraethoxysilane (TEOS) at various contents to afford chemical bondings to form silica networks and give a series of organic–inorganic hybrid coatings. They were loaded and cured on steel panels and characterized for FTIR, TGA, DSC, water contact angles (WCA), pencil hardness, surface & three‐dimensional morphological studies, and potentiodynamic polarization tests. The surfaces of the hybrid coatings showed Sea‐Island or Inverting Sea‐Island morphologies at a certain relative content of two components, which made the coatings possess hydrophobic property. Due to the contribution of organic and inorganic components, the prepared hybrid coatings possess a lot of properties such as pencil hardness, thermotolerance, and corrosion resistance. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41010.
Behavioral Health Homes: A Model for Implementation of the Affordable Care Act
Authors: Sacco Frank C. , Twemlow Stuart W.
Published: June 2014

This paper outlines a model of designing a service delivery system for a targeted population of high‐risk Medicaid families. The Affordable Care Act (ACA) has created a new focus on a population that has high behavioral health and medical needs. Medicaid families are segmented into categories based on the criteria outlined in the ACA and a service delivery system is suggested. The model calls for the creation of specialty services in the community that reach out to high‐risk families and provide ongoing integrated care that strives for improved health outcomes. The psychoanalytic principles used in attachment theory and power dynamics are offered as a method of creating new responses to complicated health and behavioral health problems in Medicaid families. Copyright © 2014 John Wiley & Sons, Ltd.
Inactivation of the Catalytic Phosphatase Domain of PTPRT/RPTPρ Increases Social Interaction in Mice
Authors: Thirtamara Rajamani Keerthi , O'Neill Brian , Han Dawn D. , Frostholm Adrienne , Rotter Andrej , Gu Howard H.
Published: June 2014

Receptor protein tyrosine phosphatase rho (RPTPρ, gene symbol PTPRT) is a transmembrane protein expressed at high levels in the developing hippocampus, olfactory bulb, cortex, and cerebellum. It has an extracellular domain that interacts with other cell adhesion molecules, and it has two intracellular phosphatase domains, one of which is catalytically active. In a recent genome‐wide association study, PTPRT was identified as a potential candidate gene for autism spectrum disorder (ASD) susceptibility. Mutation of a critical aspartate to alanine (D1046A) in the PTPRT catalytic domain inactivates phosphatase function but retains substrate binding. We have generated a knockin mouse line carrying the PTPRT D1046A mutation. The D1046A mutation in homozygous knockin mice did not significantly change locomotor activities or anxiety‐related behaviors. In contrast, male homozygous mice had significantly higher social approach scores than wild‐type animals. Our results suggest that PTPRT phosphatase function is important in modulating neural pathways involved in mouse social behaviors relevant to the symptoms in human ASD patients. Autism Res 2015, 8: 19–28. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
Enhancing fatty acid ethyl ester production in Saccharomyces cerevisiae through metabolic engineering and medium optimization
Authors: Thompson R. Adam , Trinh Cong T.
Published: June 2014

Biodiesels in the form of fatty acyl ethyl esters (FAEEs) are a promising next generation biofuel due to their chemical properties and compatibility with existing infrastructure. It has recently been shown that expression of a bacterial acyl‐transferase in the established industrial workhorse Saccharomyces cerevisiae can lead to production of FAEEs by condensation of fatty acyl‐CoAs and ethanol. In contrast to recent strategies to produce FAEEs in S. cerevisiae through manipulation of de novo fatty acid biosynthesis or a series of arduous genetic manipulations, we introduced a novel genetic background, which is comparable in titer to previous reports with a fraction of the genetic disruption by aiming at increasing the fatty acyl‐CoA pools. In addition, we combined metabolic engineering with modification of culture conditions to produce a maximum titer of over 25 mg/L FAEEs, a 40% improvement over previous reports and a 17‐fold improvement over our initial characterizations. Biotechnol. Bioeng. 2014;111: 2200–2208. © 2014 Wiley Periodicals, Inc.
A simple method for eliminating fixed‐region interference of aptamer binding during SELEX
Authors: Ouellet Eric , Lagally Eric T. , Cheung Karen C. , Haynes Charles A.
Published: June 2014

Standard libraries for systematic evolution of ligands by exponential enrichment (SELEX) typically utilize flanking regions that facilitate amplification of aptamers recovered from each selection round. Here, we show that these flanking sequences can bias the selection process, due in part to their ability to interfere with the fold or function of aptamers localized within the random region of the library sequence. We then address this problem by investigating the use of complementary oligonucleotides as a means to block aptamer interference by each flanking region. Isothermal titration calorimetry (ITC) studies are combined with fold predictions to both define the various interference mechanisms and assess the ability of added complementary oligonucleotides to ameliorate them. The proposed blocking strategy is thereby refined and then applied to standard library forms of benchmark aptamers against human α‐thrombin, streptavidin, and vascular endothelial growth factor (VEGF). In each case, ITC data show that the new method effectively removes fixed‐region mediated interference effects so that the natural binding affinity of the benchmark aptamer is completely restored. We further show that the binding affinities of properly functioning aptamers within a selection library are not affected by the blocking protocol, and that the method can be applied to various common library formats comprised of different flanking region sequences. Finally, we present a rapid and inexpensive qPCR‐based method for determining the mean binding affinity of retained aptamer pools and use it to show that introduction of the pre‐blocking method into the standard SELEX protocol results in retention of high‐affinity aptamers that would otherwise be lost during the first round of selection. Significant enrichment of the available pool of high‐affinity aptamers is thereby achieved in the first few rounds of selection. By eliminating single‐strand (aptamer‐like) structures within or involving the fixed regions, the technique is therefore shown to isolate aptamer sequence and function within the desired random region of the library members, and thereby provide a new selection method that is complementary to other available SELEX protocols. Biotechnol. Bioeng. 2014;111: 2265–2279. © 2014 Wiley Periodicals, Inc.
Biofilm growth of Chlorella sorokiniana in a rotating biological contactor based photobioreactor
Authors: Blanken W. , Janssen M. , Cuaresma M. , Libor Z. , Bhaiji T. , Wijffels R. H.
Published: June 2014

Microalgae biofilms could be used as a production platform for microalgae biomass. In this study, a photobioreactor design based on a rotating biological contactor (RBC) was used as a production platform for microalgae biomass cultivated in biofilm. In the photobioreactor, referred to as Algadisk, microalgae grow in biofilm on vertical rotating disks partially submerged in a growth medium. The objective is to evaluate the potential of the Algadisk photobioreactor with respect to the effects of disk roughness, disk rotation speed and CO2 concentration. These objectives where evaluated in relationship to productivity, photosynthetic efficiency, and long‐term cultivation stability in a lab‐scale Algadisk system. Although the lab‐scale Algadisk system is used, operation parameters evaluated are relevant for scale‐up. Chlorella Sorokiniana was used as model microalgae. In the lab‐scale Algadisk reactor, productivity of 20.1 ± 0.7 g per m2 disk surface per day and a biomass yield on light of 0.9 ± 0.04 g dry weight biomass per mol photons were obtained. Different disk rotation speeds did demonstrate minimal effects on biofilm growth and on the diffusion of substrate into the biofilm. CO2 limitation, however, drastically reduced productivity to 2–4 g per m2 disk surface per day. Productivity could be maintained over a period of 21 weeks without re‐inoculation of the Algadisk. Productivity decreased under extreme conditions such as pH 9–10, temperature above 40°C, and with low CO2 concentrations. Maximal productivity, however, was promptly recovered when optimal cultivation conditions were reinstated. These results exhibit an apparent opportunity to employ the Algadisk photobioreactor at large scale for microalgae biomass production if diffusion does not limit the CO2 supply. Biotechnol. Bioeng. 2014;111: 2436–2445. © 2014 Wiley Periodicals, Inc.
Pharmacovigilance in practice: erythropoiesis‐stimulating agents
Authors: Hedenus Michael , Ludwig Heinz , Henry David H. , Gasal Eduard
Published: June 2014

Pharmacovigilance (PV) is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or other problems related to medical products after they have been licensed for marketing. The purpose of PV is to advance the safe use of marketed medical products. Regulatory agencies and license holders collaborate to collect data reported by health care providers, patients, and the public as well as data from systematic reviews, meta‐analyses, and individual clinical and nonclinical studies. They validate and analyze the data to determine whether safety signals exist, and if warranted, develop an action plan to mitigate the identified risk. Erythropoiesis‐stimulating agents (ESAs) provide an example of how PV is applied in reality. Among other approved indications, ESAs may be used to treat anemia in patients with chemotherapy‐induced anemia. ESAs increase hemoglobin levels and reduce the need for transfusions; they are also associated with a known increased risk of thromboembolic events. Starting in 2003, emerging data suggested that ESAs might reduce survival. As a result of PV activities by regulatory agencies and license holders, labeling for ESAs addresses these risks. Meta‐analyses and individual clinical studies have confirmed that ESAs increase the risk of thromboembolic events, but when used as indicated, ESAs have not been shown to have a significant effect on survival or disease progression. Ongoing safety studies will provide additional data in the coming years to further clarify the risks and benefits of ESAs.
Successful delivery after vaginal occlusion in addition to cerclage in a trachelectomy patient with recurrent second trimester pregnancy loss: a case report
Authors: Sneider Kirstine , Poulsen Mette Østergaard , Ottosen Christian , Langhoff‐Roos Jens
Published: June 2014

Key Clinical message

Pregnancy outcome after trachelectomy has high risk of complications such as second trimester pregnancy loss and preterm birth. We report beneficial effect of a simple procedure of vaginal occlusion in addition to cerclage in a patient with trachelectomy and two prior second trimester pregnancy losses.
The effect of the setting of a positive surgical margin in soft tissue sarcoma
Authors: O'Donnell Patrick W. , Griffin Anthony M. , Eward William C. , Sternheim Amir , Catton Charles N. , Chung Peter W. , O'Sullivan Brian , Ferguson Peter C. , Wunder Jay S.
Published: June 2014

BACKGROUND

The objectives of this study were to evaluate the risk of local recurrence and survival after soft tissue sarcoma (STS) resection with positive margins and to evaluate the safety of sparing adjacent critical structures.

METHODS

One hundred sixty‐nine patients with localized STS who had positive resection margins were identified from a prospective database. Patients who had positive margins were stratified into 3 groups, each representing a specific clinical scenario: critical structure positive margin (eg major nerve, vessel, or bone), tumor bed resection positive margin, and unexpected positive margin. The rates of local recurrence‐free survival (LRFS) and cause‐specific survival (CSS) were calculated and compared with relevant control patients who had negative margins after STS resection.

RESULTS

After planned close dissection to preserve critical structures, the 5‐year LRFS and CSS rates both depended on the quality of the surgical margins (97% and 80.3%, respectively, for those with negative margins vs 85.4% and 59.4%, respectively, for those with positive margins; P = .015 and P = .05, respectively). Negative margins achieved through resection of critical structures because of tumor invasion or encasement only slightly improved the 5‐year rates of LRFS (91.2%) and CSS (63.6%; P = .8 and P = .9, respectively). The lowest 5‐year LRFS and CSS rates were 63.4% and 59.2%, respectively, after an unexpected positive margin during primary surgery.

CONCLUSIONS

After patients undergo resection of STS with positive margins, oncologic outcomes can be predicted based on the clinical context. Sparing adjacent critical structures in this setting is safe and contributes to improved functional outcomes. Cancer 2014;120:2866–2875. © 2014 American Cancer Society.
A prospective study of serum metabolites and colorectal cancer risk
Authors: Cross Amanda J. , Moore Steven C. , Boca Simina , Huang Wen‐Yi , Xiong Xiaoqin , Stolzenberg‐Solomon Rachael , Sinha Rashmi , Sampson Joshua N.
Published: June 2014

BACKGROUND

Colorectal cancer is highly prevalent, and the vast majority of cases are thought to be sporadic, although few risk factors have been identified. Using metabolomics technology, our aim was to identify biomarkers prospectively associated with colorectal cancer.

METHODS

This study included 254 incident colorectal cancers and 254 matched controls nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Serum samples were collected at baseline, and the mean length of follow‐up was 8 years. Serum metabolites were analyzed by ultra‐high performance liquid‐phase chromatography with tandem mass spectrometry, and gas chromatography coupled with mass spectrometry. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for metabolites above the limit of detection and present in at least 80% of participants.

RESULTS

A total of 676 serum metabolites were measured; of these, 447 were of known identity and 278 of these were present in >80% of individuals. Overall, there was no association between serum metabolites and colorectal cancer; however, some suggestive associations were observed between individual metabolites and colorectal cancer but none reached statistical significance after Bonferroni correction for multiple comparisons. For example, leucyl‐leucine was inversely associated (OR comparing the 90th to the 10th percentile = 0.50; 95% CI = 0.32‐0.80; P = .003). In sex‐stratified analyses, serum glycochenodeoxycholate was positively associated with colorectal cancer among women (OR90th vs.10th percentile = 5.34; 95% CI = 2.09‐13.68; P = .0001).

CONCLUSIONS

No overall associations were observed between serum metabolites and colorectal cancer, but serum glycochenodeoxycholate, a bile acid metabolite, was positively associated with colorectal cancer among women. Cancer 2014;120:3049–3057. © 2014 American Cancer Society.
Different rates of DNA replication at early versus late S‐phase sections: Multiscale modeling of stochastic events related to DNA content/EdU (5‐ethynyl‐2′deoxyuridine) incorporation distributions
Authors: Li Biao , Zhao Hong , Rybak Paulina , Dobrucki Jurek W. , Darzynkiewicz Zbigniew , Kimmel Marek
Published: June 2014

Mathematical modeling allows relating molecular events to single‐cell characteristics assessed by multiparameter cytometry. In the present study we labeled newly synthesized DNA in A549 human lung carcinoma cells with 15–120 min pulses of EdU. All DNA was stained with DAPI and cellular fluorescence was measured by laser scanning cytometry. The frequency of cells in the ascending (left) side of the “horseshoe”‐shaped EdU/DAPI bivariate distributions reports the rate of DNA replication at the time of entrance to S phase while their frequency in the descending (right) side is a marker of DNA replication rate at the time of transition from S to G2 phase. To understand the connection between molecular‐scale events and scatterplot asymmetry, we developed a multiscale stochastic model, which simulates DNA replication and cell cycle progression of individual cells and produces in silico EdU/DAPI scatterplots. For each S‐phase cell the time points at which replication origins are fired are modeled by a non‐homogeneous Poisson Process (NHPP). Shifted gamma distributions are assumed for durations of cell cycle phases (G1, S and G2M), Depending on the rate of DNA synthesis being an increasing or decreasing function, simulated EdU/DAPI bivariate graphs show predominance of cells in left (early‐S) or right (late‐S) side of the horseshoe distribution. Assuming NHPP rate estimated from independent experiments, simulated EdU/DAPI graphs are nearly indistinguishable from those experimentally observed. This finding proves consistency between the S‐phase DNA‐replication rate based on molecular‐scale analyses, and cell population kinetics ascertained from EdU/DAPI scatterplots and demonstrates that DNA replication rate at entrance to S is relatively slow compared with its rather abrupt termination during S to G2 transition. Our approach opens a possibility of similar modeling to study the effect of anticancer drugs on DNA replication/cell cycle progression and also to quantify other kinetic events that can be measured during S‐phase. © 2014 International Society for Advancement of Cytometry
Perirenal myelolipoma diagnosed on imprint: Case report and review of the literature
Authors: Brandler Tamar C. , Reder Ilan , Kahn Leonard
Published: June 2014

Myelolipomas are benign tumors containing adipose tissue and hematopoeitic elements which occur most commonly in the adrenal glands. Extra‐adrenal myelolipomas are uncommon with few cases of renal and perirenal myelolipomas in the literature. These cases may be difficult to diagnose based on radiology alone and intraoperative diagnosis can be extremely important in determining the course of surgery. Due to the lipomatous component of the tumor it may be technically difficult to prepare adequate frozen sections; this problem can be obviated by utilization of cytologic imprint preparations. We present a case of perirenal myelolipoma diagnosed intraoperatively utilizing cytologic imprint preparations stained with toluidine blue and hematoxylin and eosin. Diagn. Cytopathol. 2015;43:230–233. © 2014 Wiley Periodicals, Inc.
Generation of mice carrying a knockout‐first and conditional‐ready allele of transforming growth factor beta2 gene
Authors: Ishtiaq Ahmed A. S. , Bose Gracelyn C. , Huang Li , Azhar Mohamad
Published: June 2014

Transforming growth factor beta2 (TGFβ2) is a multifunctional protein which is expressed in several embryonic and adult organs. TGFB2 mutations can cause Loeys Dietz syndrome, and its dysregulation is involved in cardiovascular, skeletal, ocular, and neuromuscular diseases, osteoarthritis, tissue fibrosis, and various forms of cancer. TGFβ2 is involved in cell growth, apoptosis, cell migration, cell differentiation, cell‐matrix remodeling, epithelial‐mesenchymal transition, and wound healing in a highly context‐dependent and tissue‐specific manner. Tgfb2−/− mice die perinatally from congenital heart disease, precluding functional studies in adults. Here, we have generated mice harboring Tgfb2βgeo (knockout‐first lacZ‐tagged insertion) gene‐trap allele and Tgfb2flox conditional allele. Tgfb2βgeo/βgeo or Tgfb2βgeo/‐ mice died at perinatal stage from the same congenital heart defects as Tgfb2−/− mice. β‐galactosidase staining successfully detected Tgfb2 expression in the heterozygous Tgfb2βgeo fetal tissue sections. Tgfb2flox mice were produced by crossing the Tgfb2+/βgeo mice with the FLPeR mice. Tgfb2flox/− mice were viable. Tgfb2 conditional knockout (Tgfb2cko/−) fetuses were generated by crossing of Tgfb2flox/− mice with Tgfb2+/−; EIIaCre mice. Systemic Tgfb2cko/− embryos developed cardiac defects which resembled the Tgfb2βgeo/βgeo, Tgfb2βgeo/−, and Tgfb2−/− fetuses. In conclusion, Tgfb2βgeo and Tgfb2flox mice are novel mouse strains which will be useful for investigating the tissue specific expression and function of TGFβ2 in embryonic development, adult organs, and disease pathogenesis and cancer. genesis 52:817–826, 2014. © 2014 Wiley Periodicals, Inc.
Both retention and recirculation contribute to long‐lived regulatory T‐cell accumulation in the thymus
Authors: Yang EnJun , Zou Tao , Leichner Theresa M. , Zhang Shirley L. , Kambayashi Taku
Published: June 2014

Natural Treg cells acquire their lineage‐determining transcription factor Foxp3 during development in the thymus and are important in maintaining immunologic tolerance. Here, we analyzed the composition of the thymic Treg‐cell pool using RAG2‐GFP/FoxP3‐RFP dual reporter mice and found that a population of long‐lived GFP− Treg cells exists in the thymus. These long‐lived Treg cells substantially increased with age, to a point where they represent >90% of the total thymic Treg‐cell pool at 6 months of age. In contrast, long‐lived conventional T cells remained at ∼15% of the total thymic pool at 6 months of age. Consistent with these studies, we noticed that host‐derived Treg cells represented a large fraction (∼10%) of the total thymic Treg‐cell pool in bone marrow chimeras, suggesting that long‐lived Treg cells also reside in the thymus of these mice. The pool of long‐lived Treg cells in the thymus was sustained by retention of Treg cells in the thymus and by recirculation of peripheral Treg cells back into the thymus. These long‐lived thymic Treg cells suppressed T‐cell proliferation to an equivalent extent to splenic Treg cells. Together, these data demonstrate that long‐lived Treg cells accumulate in the thymus by both retention and recirculation.
Reactivity Study of a Chlorostannylene Derived from Bis(iminophosphoranyl)methane
Authors: Leung Wing‐Por , Kan Kwok‐Wai , Chan Yuk‐Chi , Mak Thomas C. W.
Published: June 2014

The reactivity of the chlorostannylene [HC(PPh2=NSiMe3)2SnCl] (2) with various substrates has been investigated. Compound 2 acts as a two‐electron carbene‐like ligand and forms a complex with W(CO)5THF (THF = tetrahydrofuran) to give [HC(PPh2=NSiMe3)2(Cl)Sn→W(CO)5] (4). It reacts with benzil and 3,5‐di‐tert‐butyl‐o‐benzoquinone to give the oxidative cycloaddition products [HC(PPh2=NSiMe3)2(Cl)Sn{O(Ph)C=C(Ph)O}] (5) and [HC(PPh2=NSiMe3)2(Cl)Sn{O(3,5‐di‐tBu‐C6H2)O}] (6), respectively. The metathesis reaction of 2 with excess sodium azide affords [HC(PPh2=NSiMe3)2SnN3] (7). With silver(I) triflate, it forms an ionic triflate salt [HC(PPh2=NSiMe3)2Sn][CF3O2SO] (8), which features an exceptionally long Sn···OSO3CF3 distance. It can act as a ligand‐transfer reagent by reacting with [Fe{N(SiMe3)2}2] to give [HC(PPh2=NSiMe3)2Fe(μ‐Cl)]2 (9). The X‐ray structures of 2–9 have been determined.
Sterically Controlled Synthesis and Nucleophilic Substitution Reactions of Di‐ and Trimeric N‐Heterocyclic Phosphenium Metal(0) Halides
Authors: Nickolaus Jan , Bender Johannes , Nieger Martin , Gudat Dietrich
Published: June 2014

The reaction of symmetrical bis(diazaphospholenyl) compounds with [MCl2(cod)] (M = Pd, Pt; cod = 1,5‐cyclooctadiene) has been used to prepare N‐heterocyclic phosphenium (NHP) metal(0) halides [M(NHP)Cl]n with diverse N substituents. Characterisation by ESI‐MS and NMR spectroscopy revealed that N‐tBu‐ and N‐aryl‐substituted NHP precursors yield trimeric (n = 3) and dimeric (n = 2) products, respectively; the degree of aggregation is presumably controlled by the different steric requirements of the NHP moiety. A single‐crystal XRD study of a trimeric Pd complex confirmed the proposed constitution of the complexes with μ2‐bridging NHP and terminal chlorido ligands and allowed their metrical parameters to be analysed for the first time undisturbed by crystallographic disorder. Studies of ligand substitution and redistribution processes revealed that the complexes withstand exchange of the μ‐bridging NHP units but tolerate substitution of the terminal chlorido ligands by other strong nucleophiles (SCN–, I–) with conservation of the oligomeric framework. Attempts to replace chlorido by thiolato ligands led to the discovery of a reaction between a phosphenium metal thiolate [Pd(NHP)(SR)]3 and CH2Cl2 to give a formaldehyde dithioacetal H2C(SR)2 (R = benzyl). This reaction could be developed into a protocol for a C–S cross‐coupling reaction in the presence of a catalytic amount of the phosphenium complex.
Experimental and First‐Principles Studies of the Ternary Borides Ta3Ru5B2 and M3–xRu5+xB2 (M = Zr, Hf)
Authors: Hermus Martin , Fokwa Boniface P. T.
Published: June 2014

Ta3Ru5B2, Zr2.86(5)Ru5.14(5)B2, and Hf2.83(2)Ru5.17(2)B2 have been successfully synthesized as polycrystalline powders as well as single crystals and characterized by powder and single‐crystal X‐ray diffraction and EDX analysis. Furthermore, their electronic structures and bonding characteristics have been analyzed by DFT calculations. The three phases are isotypic and crystallize with a Ti3Co5B2‐type structure (space group P4/mbm). Their electronic densities of states, which all possess a large pseudogap at the Fermi level, closely follow the rigid band model. Bonding analyses indicated that Ru–B and Ru–M (M = Zr, Hf, Ta) heteroatomic interactions are mainly responsible for their structural stability and that the homoatomic M–M interactions behave differently when connecting either two tetragonal or two pentagonal Ru prisms at the same distance.