bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation and application of sulfadiazine surface molecularly imprinted polymers with temperature‐responsive properties
Authors: Ma Pengfei , Zhou Zhiping , Yang Wenming , Tang Bingqing , Liu Hong , Xu Wanzhen , Huang Weihong
Published: December 2014

Novel, temperature‐responsive molecularly imprinted polymers (TMIPs) based on potassium hexatitanate whiskers for selectively adsorbing sulfadiazine (SDZ) from aqueous media were prepared with methacrylic acid (MAA) and 4‐vinylpyridine (4‐VP) as cofunctional monomers and N‐isopropyl acrylamide (NIPAM) as a temperature‐responsive monomer. The template–monomer interactions were studied by molecular simulation. In particular, the effects of different kinds of crosslinkers on the selective recognition ability of the TMIPs in water media were investigated. The temperature–responsive adsorption performance and phase behavior of the molecularly imprinted polymers were studied by batch‐mode binding experiments, swelling experiments, and contact angle testing. The results demonstrate that the combination of MAA, 4‐VP, and NIPAM was a favorable temperature‐responsive imprinted system for SDZ in water, and the cocrosslinking agent of ethylene glycol dimethacrylate (EGDMA) and N,N′‐methylene bisacrylamide (MBA) was more suitable compared with either pure EGDMA or MBA. The adsorption kinetics and adsorption isotherms were analyzed by the fitting of different adsorption models. Also, the effect of the temperature on the recovery was investigated by the determination of the spiked SDZ in real‐water samples with solid‐phase extraction and high‐performance liquid chromatography. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41769.
Ion‐transport study in nanocomposite solid polymer electrolytes based on chitosan: Electrical and dielectric analysis
Authors: Aziz Shujahadeen B. , Abidin Zul Hazrin Z.
Published: December 2014

In this study, (1.1111 − x)(0.9CS–0.1NaTf)xAl2O3(0.02 ≤ x ≤ 0.1) [where CS is chitosan, NaTf is sodium triflate (NaCF3SO3), and Al2O3 is aluminum oxide] nanocomposite solid polymer electrolyte (SPE) films based on CS were prepared by a solution casting technique. X‐ray diffraction and scanning electron microscopy analysis revealed that the alumina nanoparticles had a great effect on the structural and morphological behavior of the CS–NaTf (90:10) polymer electrolyte. An investigation of the electrical and dielectric parameters of the nanocomposite SPE films was conducted. Electrical impedance spectroscopy was carried out for this purpose. The relationships between the electrical and dielectric parameters were used to interpret and understand the ion‐conduction mechanism. We observed that the direct‐current conductivity (σdc) and dielectric constant followed the same trend with salt concentration. σdc versus temperature showed the Arrhenius and Vogel‐Fulcher‐Tammann (VTF) regions. The drops of σdc at high temperatures were observed for all of the samples. The ion relaxation dynamics were studied from Argand plots. For the first time, we confirmed the existence of a strong experimental relationship between the high‐frequency semicircle of the impedance plots and the high‐frequency dispersion regions of the alternating‐current conductivity (σac). The dispersion regions of σac were used to study the ion‐conduction mechanism. The behavior of the frequency exponent as a function of the temperature was used to interpret σdc versus the temperature. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41774.
Development and characterization of gelatin–polysaccharide based phase‐separated hydrogels for prevention of sexually transmitted diseases
Authors: Singh Vinay Kumar , Sagiri Sai Sateesh , Khade Shankar Mukund , Bhattacharya Mrinal Kanti , Pal Kunal
Published: December 2014

Bacterial vaginosis is a sexually transmitted vaginal infection prevalent in sexually active women. Gelatin–polysaccharide phase‐separated hydrogels were prepared and characterized as vaginal delivery systems for the treatment of bacterial vaginosis. Sodium carboxymethyl cellulose, maltodextrin, and dextran were used as the representative polysaccharides. The developed gels were characterized by impedance spectrometer, X‐ray diffraction (XRD) studies, and differential scanning calorimetry. The mucoadhesivity, water absorption, and hemocompatibility of the gels were also studied. The gels were electrically conductive in nature and showed a concentration‐dependent behavior. XRD study suggested the amorphous nature of the hydrogels. An increase in the polysaccharide content increased the water holding capacity of the gels. The gels were found to possess mucoadhesive property and were hemocompatible. Metronidazole, a commonly used drug for treating bacterial vaginosis, loaded gels showed diffusion‐mediated drug release. The drug‐loaded hydrogels showed good antimicrobial activity. In gist, the developed hydrogels may be tried as matrices for vaginal delivery of antimicrobials. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2015,132, 41785.
Combination of temperature and saturated vapor annealing for phase separation of block copolymer
Authors: Švanda Jan , Lyutakov Oleksiy , Vosmanská Vladimíra , Švorčík Václav
Published: December 2014

Phase separation of block copolymer films is a perspective technique for the creation of nanostructured templates. The phase separation can be induced by thermal or vapor solvent annealing. However, a standardized and reproducible technique of the phase separation is still missing, even though many papers describing various experimental conditions. In this article we have tried to develop standardized and reproducible technique of the phase separation, which can be easily scaled up. For this purpose we used the combination of the thermal and vapor annealing of poly(styrene‐b‐4‐vinylpyridine) copolymer films on a glass substrate under static conditions. The technique was tailored by the choice of optimal solvent for the vapor annealing, based on the solvent–polymer interaction. Finally, the films were reconstructed by immersing in methanol or ethanol and stretching of the P4VP component during the reconstruction was investigated by the angle‐resolved X‐ray photoelectron spectroscopy. Morphology of the films was investigated by the atomic force microscopy and confocal microscopy. The kinetics of the phase separation was also studied. The presented combined technique of the thermal and vapor annealing can be easily temperature‐controlled for reproducibly obtaining the films of a desired morphology. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41853.
New 14C dates for Spring Creek and Mowbray Swamp megafauna: XAD‐2 processing
Authors: Gillespie Richard , Wood Rachel , Fallon Stewart , Stafford Thomas W. , Southon John
Published: December 2014

Bones from extinct Australian marsupials found at Spring Creek, Victoria, and in the Mowbray Swamp, Tasmania, have yielded scattered and anomalously young radiocarbon ages measured on collagen, gelatin or ultrafiltered gelatin. We resampled previously dated material from those two sites and from Mt Cripps, Tasmania, as well as a control sample from Zaglik, Russia, to compare chronologies based on XAD‐2 purified total amino acid fractions and collagen purified by ultrafiltration (UF) or less rigorous methods. Our age from the control site bone gave a similar infinite age, while six out of seven other comparisons yielded radiocarbon ages on total amino acid fractions older than those previously measured on collagen or gelatin. The Palorchestes from Spring Creek yielded a date of >53500 BP.
Stereotypic Rheumatoid Factors That Are Frequently Expressed in Mucosa‐Associated Lymphoid Tissue–Type Lymphomas Are Rare in the Labial Salivary Glands of Patients With Sjögren's Syndrome
Authors: Bende Richard J. , Slot Linda M. , Hoogeboom Robbert , Wormhoudt Thera A. M. , Adeoye Akanbi O. , Guikema Jeroen E. J. , van Noesel Carel J. M.
Published: December 2014

Objective

Among autoimmune diseases, Sjögren's syndrome (SS) is most strongly associated with the development of malignant B cell lymphoma, in particular mucosa‐associated lymphoid tissue (MALT)–type lymphoma. Previously, we have shown that in ∼40% of cases of salivary gland MALT lymphoma, high‐affinity stereotypic rheumatoid factor (RF) B cell receptors, specific for IgG‐Fc, are expressed. This study was undertaken to investigate whether in the inflamed salivary glands of patients with SS, a similar RF‐biased Ig repertoire is present.

Methods

Extensive analyses of the B cell Ig VH region repertoire were performed on microdissected tissue samples from the labial salivary glands of 4 patients with SS.

Results

All SS labial salivary glands harbored expanded B cell clones, of which 1 or 2 were highly expanded and detected in >50% of the microdissected samples. However, among the identified 464 distinct Ig clonotypes, only 3 stereotypic RF–expressing clones were detected. In 2 patients with SS, an RF‐expressing clone was detected at low frequency in 1 of the microdissected samples, whereas 1 patient with SS harbored a highly expanded RF‐expressing clone that was detected in all microdissected samples and also detected in the peripheral blood. Two years after analysis of this sample, the latter patient developed a diffuse large B cell lymphoma originating from the same RF clone.

Conclusion

Inflamed labial salivary glands in patients with SS generally harbor 1 or 2 highly expanded B cell clones. The repertoire strongly biased toward stereotypic RFs in salivary gland MALT lymphomas is not a reflection of a similar repertoire in the inflamed salivary glands of patients with SS; rather, in the latter, the repertoire is based on a strong selection advantage of incidental stereotypic RF–expressing B cells.
A Large National Cohort of French Patients With Chronic Recurrent Multifocal Osteitis
Authors: Wipff J. , Costantino F. , Lemelle I. , Pajot C. , Duquesne A. , Lorrot M. , Faye A. , Bader‐Meunier B. , Brochard K. , Despert V. , Jean S. , Grall‐Lerosey M. , Marot Y. , Nouar D. , Pagnier A. , Quartier P. , Job‐Deslandre C.
Published: December 2014

Objective

To document more fully the characteristics of chronic recurrent multifocal osteomyelitis (CRMO) in pediatric patients, to collect data on the outcomes and management of the disease, and to define prognostic factors.

Methods

One hundred seventy‐eight patients were included (123 female patients and 55 male patients), with a mean ± SD age at diagnosis of 10.9 ± 2.9 years. Inclusion criteria were a diagnosis of CRMO, evidence of at least one lesion of osteitis confirmed by imaging, and development of the syndrome before age 18 years.

Results

Longitudinal clinical and imaging studies revealed that only 12 of 178 CRMO patients (7%) had unifocal lesions at the last medical visit. We were able to apply the clinical chronic nonbacterial osteomyelitis score to 110 of 178 patients (62%), which indicated that bone biopsy could have been avoided in 27 cases (25%). At the last medical visit, disease was in remission in only 73 of 171 patients (43%) (41% receiving therapy) after a mean ± SD of 47.9 ± 38.9 months; 44 of 171 patients (26%) experienced sequelae. Using cluster analysis, the CRMO cohort was separated into 3 homogeneous phenotypes (severe, mild, and intermediate). Patients with the severe phenotype had the worst prognosis. This group was entirely composed of male patients, most of whom had the multifocal form of CRMO and inflammatory syndrome. Patients with the mild phenotype had the best prognosis. This group was primarily composed of female patients with a unifocal form of CRMO and infrequent clavicle involvement and inflammatory syndrome. Patients with the intermediate phenotype had a good prognosis but greater reliance on treatment. This group primarily included female patients with multifocal lesions and inflammatory syndrome.

Conclusion

This is the largest CRMO cohort described in the literature to date. Clinical evolution and imaging investigations confirmed the multifocal pattern of the disease. Three distinct subgroups of CRMO patients were distinguished, with very different prognoses.
High Fidelity Between Saliva Proteomics and the Biologic State of Salivary Glands Defines Biomarker Signatures for Primary Sjögren's Syndrome
Authors: Delaleu Nicolas , Mydel Piotr , Kwee Ivo , Brun Johan G. , Jonsson Malin V. , Jonsson Roland
Published: December 2014

Objective

Dependence on invasive procedures for classification of patients with Sjögren's syndrome (SS) hampers timely diagnosis and suitable patient followup. The aim of this study was to recapitulate the diagnosis of SS through noninvasive means and to define the biologic state of SS patients' salivary glands.

Methods

Using a 187‐plex capture antibody–based assay, salivary proteomic biomarker profiles were generated from patients with primary SS, patients with rheumatoid arthritis, and asymptomatic controls. Discriminant function analyses and Gene Ontology–based network analyses allowed data analyses with a reductionist approach and with a focus on systems biology.

Results

Characterized by significant changes in 61 and 55 proteins, respectively, the salivary proteome of SS patients appeared profoundly altered compared to that of individuals without SS. On this basis, 4‐plex and 6‐plex biomarker signatures, both including interleukin‐4 (IL‐4), IL‐5, and clusterin, achieved accurate prediction of an individual's group membership for at least 94% of cases. Of note, all misclassified SS patients presented with ectopic germinal center–like structures. Systematic inference of biologic meaning identified SS‐related protein patterns delineating B cell–dominated immune responses, macrophage differentiation, and signs of T cell chemotaxis. In addition, proteomic Multi‐Analyte Profiles provided insight about proteins related to collagen, cytokine, and growth factor synthesis as well as lipid transport.

Conclusion

The SS‐related molecular landscape conveyed by saliva showed great congruence with histopathologic features found in SS and advances understanding of this disease at a molecular level. Such salivary biomarker signatures harbor great potential for improving timeliness of SS diagnosis and enabling suitable patient followup.
A traffic assignment model for a ridesharing transportation market
Authors: Xu Huayu , Ordóñez Fernando , Dessouky Maged
Published: December 2014

A nascent ridesharing industry is being enabled by new communication technologies and motivated by the many possible benefits, such as reduction in travel cost, pollution, and congestion. Understanding the complex relations between ridesharing and traffic congestion is a critical step in the evaluation of a ridesharing enterprise or of the convenience of regulatory policies or incentives to promote ridesharing. In this work, we propose a new traffic assignment model that explicitly represents ridesharing as a mode of transportation. The objective is to analyze how ridesharing impacts traffic congestion, how people can be motivated to participate in ridesharing, and, conversely, how congestion influences ridesharing, including ridesharing prices and the number of drivers and passengers. This model is built by combining a ridesharing market model with a classic elastic demand Wardrop traffic equilibrium model. Our computational results show that (i) the ridesharing base price influences the congestion level, (ii) within a certain price range, an increase in price may reduce the traffic congestion, and (iii) the utilization of ridesharing increases as the congestion increases. Copyright © 2014 John Wiley & Sons, Ltd.
High yields of active Thermus thermophilus proline dehydrogenase are obtained using maltose‐binding protein as a solubility tag
Authors: Huijbers Mieke M.E. , van Berkel Willem J.H.
Published: December 2014

Proline dehydrogenase (ProDH) catalyzes the FAD‐dependent oxidation of proline to Δ1‐pyrroline‐5‐carboxylate, the first step of proline catabolism in many organisms. Next to being involved in a number of physiological processes, ProDH is of interest for practical applications because the proline imino acid can serve as a building block for a wide range of peptides and antibiotics. ProDH is a membrane‐associated protein and recombinant soluble forms of the enzyme have only been obtained in limited amounts. We here report on the heterologous production of ProDH from Thermus thermophilus (TtProDH) in Escherichia coli. Using maltose‐binding protein as solubility tag, high yields of active holoenzyme are obtained. Native TtProDH can be produced from cleaving the purified fusion protein with trypsin. Size‐exclusion chromatography shows that fused and clipped TtProDH form oligomers. Thermal stability and co‐solvent tolerance indicate the conformational robustness of TtProDH. These properties together with the high yield make TtProDH attractive for industrial applications.
A macrokinetic model‐based comparative meta‐analysis of recombinant protein production by Pichia pastoris under AOX1 promoter
Authors: Barrigon José Manuel , Valero Francisco , Montesinos José Luis
Published: December 2014

An unstructured macrokinetic model for heterologous production of Rhizopus oryzae lipase (ROL) by a Pichia pastoris PAOX1 based system was developed. Mean specific rates and state variables for various fed‐batch cultures, under methanol limited and non‐limited conditions were used for modeling. The most representative kinetic functions (viz., Monod, Haldane, Pirt and Luedeking‐Piret) were used for the specific rates of cell growth (µ), substrate consumption (qS) and product formation (qP). The performance of two different process models was assessed via simulation tests, using an overall validation procedure. The best model describes the cellular growth by a non‐monotonic substrate function, substrate uptake via Pirt's equation and product formation through a Luedeking‐Piret equation. A comparative meta‐analysis of heterologous protein production of various target proteins by Pichia pastoris under AOX1 promoter was conducted and a general strategy for improving protein production from process kinetics was developed as a key to bioprocess optimization. Biotechnol. Bioeng. 2015;112: 1132–1145. © 2015 Wiley Periodicals, Inc.
Changes in glucose fermentation pathways by an enriched bacterial culture in response to regulated dissolved H2 concentrations
Authors: Zheng Hang , Zeng Raymond J. , Duke Mikel C. , O'Sullivan Cathryn A. , Clarke William P.
Published: December 2014

It is well established that metabolic pathways in the fermentation of organic waste are primarily controlled by dissolved H2 concentrations, but there is no reported study that compares observed and predicted shifts in fermentation pathways induced by manipulating the dissolved H2 concentration. A perfusion system is presented that was developed to control dissolved H2 concentrations in the continuous fermentation of glucose by a culture highly enriched towards Thermoanaerobacterium thermosaccharolyticum (86 ± 9% relative abundance) from an originally diverse consortia in the leachate of a laboratory digester fed with municipal solid waste. Media from a 2.5 L CSTR was drawn through sintered steel membrane filters to retain biomass, allowing vigorous sparging in a separate chamber without cellular disruption. Through a combination of sparging and variations in glucose feeding rate from 0.8 to 0.2 g/L/d, a range of steady state fermentations were performed with dissolved H2 concentrations as low as an equivalent equilibrated H2 partial pressure of 3 kPa. Trends in product formation rates were simulated using a H2 regulation partitioning model. The model correctly predicted the direction of products redistribution in response to H2 concentration changes and the acetate and butyrate formation rates when H2 concentrations were less than 6 kPa. However, the model over‐estimated acetate, ethanol and butanol productions at the expense of butyrate production at higher H2 concentrations. The H2 yield at the lowest dissolved H2 concentration was 2.67 ± 0.08 mol H2/mol glucose, over 300% higher than the yield achieved in a CSTR operated without sparging. Biotechnol. Bioeng. 2015;112: 1177–1186. © 2014 Wiley Periodicals, Inc.
Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring
Authors: Sussman Dafna , Germann Jurgen , Henkelman Mark
Published: December 2014

Introduction

The ketogenic diet (KD) has seen an increase in popularity for clinical and non‐clinical purposes, leading to rise in concern about the diet's impact on following generations. The KD is known to have a neurological effect, suggesting that exposure to it during prenatal brain development may alter neuro‐anatomy. Studies have also indicated that the KD has an anti‐depressant effect on the consumer. However, it is unclear whether any neuro‐anatomical and/or behavioral changes would occur in the offspring and persist into adulthood.

Methods

To fill this knowledge gap we assessed the brain morphology and behavior of 8‐week‐old young‐adult CD‐1 mice, who were exposed to the KD in utero, and were fed only a standard‐diet (SD) in postnatal life. Standardized neuro‐behavior tests included the Open‐Field, Forced‐Swim, and Exercise Wheel tests, and were followed by post‐mortem Magnetic Resonance Imaging (MRI) to assess brain anatomy.

Results

The adult KD offspring exhibit reduced susceptibility to anxiety and depression, and elevated physical activity level when compared with controls exposed to the SD both in utero and postnatally. Many neuro‐anatomical differences exist between the KD offspring and controls, including, for example, a cerebellar volumetric enlargement by 4.8%, a hypothalamic reduction by 1.39%, and a corpus callosum reduction by 4.77%, as computed relative to total brain volume.

Conclusions

These results suggest that prenatal exposure to the KD programs the offspring neuro‐anatomy and influences their behavior in adulthood.
Sustainable Development in Supply Chain Management: The Role of Organizational Learning for Policy Implementation
Authors: Oelze Nelly , Hoejmose Stefan Ulstrup , Habisch Andre , Millington Andrew
Published: December 2014

Implementing sustainable policies in supply chains is a significant challenge for businesses. Recent evidence has shown that failure to manage supply chains responsibly can have significant impacts on firms' reputation and financial performance. In this paper, we develop a conceptual framework, which focuses on organizational learning, and outline specific channels through which firms can generate learning processes and build appropriate capabilities to successfully implement social and environmental supply chain policies. Drawing on 57 in‐depth interviews from a cross‐sectional sample of seven UK and nine German companies, we empirically assess our conceptual framework in accordance with a grounded, in‐depth case study analysis approach. We find compelling evidence to suggest that organizational learning is an important factor for a successful implementation of sustainable supply chain management. Organizational learning is often established as a result of training, knowledge acquisition, stakeholder engagement and collaboration between intra‐organizational and inter‐organizational partners, including suppliers and NGOs. Nonetheless, our results also emphasize that firms often have few systematic processes through which organizational learning is developed, and that such learning processes are often ad hoc at best, which in turn has significant implications for the responsible supply chain practices. Copyright © 2014 John Wiley & Sons, Ltd and ERP Environment
Good communication should permeate every aspect of campus safety
Authors: Gomez Cynthia
Published: December 2014

Mike Wilwol is a man who likes to try new things. So after working in municipal policing, fire, emergency medical services, emergency management and hospital security over two decades, he decided to make the leap into campus safety. Last year, he accepted a position as director of campus safety at Cornell College.
Make organizational achievement the organizational standard
Authors: Skipworth Stanley
Published: December 2014

Completing an independent benchmarking initiative or attaining an industry‐specific threshold of sound performance is likely to lead to a renewed and deepened appreciation for the job being done and the organization's mission among members of your campus safety team. But beyond that, pursuing key accomplishments and milestones can be a powerful and reaffirming tool to help us ensure lasting success and improvement for our departments.
Develop comprehensive plan for preventing, addressing workplace violence
Authors: Gomez Cynthia
Published: December 2014

Developing a program to address workplace violence can not only help you create a more welcoming campus for those who work and study at your institution, but can also help you prevent everything from harassment to the dreaded active‐shooter scenario. CPI, a behavior management consulting firm that has worked with many institutions to prevent and address workplace violence, can help you do that through its “Promoting Safety on Campus” e‐booklet. Below are just a few of the many tips offered in the document.
Encapsulation of Heteropolyanion‐Based Ionic Liquid within the Metal–Organic Framework MIL‐100(Fe) for Biodiesel Production
Authors: Wan Hui , Chen Chong , Wu Zuowang , Que Yigen , Feng Yu , Wang Wei , Wang Lei , Guan Guofeng , Liu Xiaoqin
Published: December 2014

The front cover artwork for Issue 3/2015 has been provided by a research group from the State Key Laboratory of Materials‐Oriented Chemical Engineering, Nanjing Tech University. The image depicts a new strategy to construct a composite of an ionic liquid, a polyoxometalate, and a metal–organic framework. See the Full Paper itself at http://dx.doi.org/10.1002/cctc.201402800.
Mass Spectrometric Characterization of Methylaluminoxane‐Activated Metallocene Complexes
Authors: Trefz Tyler K. , Henderson Matthew A. , Linnolahti Mikko , Collins Scott , McIndoe J. Scott
Published: December 2014

Electrospray‐ionization mass spectrometric studies of poly(methylaluminoxane) (MAO) in the presence of [Cp2ZrMe2], [Cp2ZrMe(Cl)], and [Cp2ZrCl2] in fluorobenzene (PhF) solution are reported. The results demonstrate that alkylation and ionization are separate events that occur at competitive rates in a polar solvent. Furthermore, there are significant differences in ion‐pair speciation that result from the use of metallocene dichloride complexes in comparison to alkylated precursors at otherwise identical Al/Zr ratios. Finally, the counter anions that form are dependent on the choice of precursor and Al/Zr ratio; halogenated aluminoxane anions [(MeAlO)x(Me3Al)y−z(Me2AlCl)zMe]− (z=1, 2, 3…︁) are observed using metal chloride complexes and under some conditions may predominate over their non‐halogenated precursors [(MeAlO)x(Me3Al)yMe]−. Specifically, this halogenation process appears selective for the anions that form in comparison to the neutral components of MAO. Only at very high Al/Zr ratios is the same “native” anion distribution observed when using [Cp2ZrCl2] when compared with [Cp2ZrMe2]. Together, the results suggest that the need for a large excess of MAO when using metallocene dichloride complexes is a reflection of competitive alkylation vs. ionization, the persistence of unreactive, homodinuclear ion pairs in the case of [Cp2ZrCl2], as well as a change in ion pairing resulting from modification of the anions formed at lower Al/Zr ratios. Models for neutral precursors and anions are examined computationally.
Synthesis of Pyrrolidine Derivatives by a Platinum/Brønsted Acid Relay Catalytic Cascade Reaction
Authors: Galván Alicia , Calleja Jonás , Fañanás Francisco J. , Rodríguez Félix
Published: December 2014

A new catalytic reaction for the synthesis of pyrrolidine derivatives is presented. The method implies the coupling of N‐Boc‐protected alkynamine derivatives and appropriate alkenes or alkynes in a process catalysed by a platinum/triflic acid catalytic binary system. This reaction is believed to proceed through a cascade process implying an initial platinum‐catalysed cycloisomerization of the alkynamine derivative followed by a triflic acid promoted nucleophilic addition of the alkene or alkyne and trapping of the cationic species formed by the Boc group. Not only simple alkenes and alkynes were used in this reaction but also allyltrimethylsilane and propargyltrimethylsilane. Particularly, when allyltrimethylsilane is used as the alkene counterpart interesting bicyclic compounds containing a trimethylsilane group are obtained. However, when propargyltrimethylsilane is used in the presence of water we observed the formation of a related bicyclic compound lacking the trimethylsilane group and containing an exocyclic carboncarbon bond.
Gold(I)‐Catalyzed Cycloisomerizations and Alkoxycyclizations of ortho‐(Alkynyl)styrenes
Authors: Sanjuán Ana M. , Rashid Muhammad A. , García‐García Patricia , Martínez‐Cuezva Alberto , Fernández‐Rodríguez Manuel A. , Rodríguez Félix , Sanz Roberto
Published: December 2014

Indenes and related polycyclic structures have been efficiently synthesized by gold(I)‐catalyzed cycloisomerizations of appropriate ortho‐(alkynyl)styrenes. Disubstitution at the terminal position of the olefin was demonstrated to be essential to obtain products originating from a formal 5‐endo‐dig cyclization. Interestingly, a complete switch in the selectivity of the cyclization of o‐(alkynyl)‐α‐methylstyrenes from 6‐endo to 5‐endo was observed by adding an alcohol to the reaction media. This allowed the synthesis of interesting indenes bearing an all‐carbon quaternary center at C1. Moreover, dihydrobenzo[a]fluorenes can be obtained from substrates bearing a secondary alkyl group at the β‐position of the styrene moiety by a tandem cycloisomerization/1,2‐hydride migration process. In addition, diverse polycyclic compounds were obtained by an intramolecular gold‐catalyzed alkoxycyclization of o‐(alkynyl)styrenes bearing a nucleophile in their structure. Finally, the use of a chiral gold complex allowed access to elusive chiral 1H‐indenes in good enantioselectivities.
BODIPY‐Based Fluorescent Thermometer as a Lysosome‐Targetable Probe: How the Oligo(ethylene glycols) Compete Photoinduced Electron Transfer
Authors: Wang Hua , Wu Yongquan , Shi Yanlin , Tao Pan , Fan Xing , Su Xinyan , Kuang Gui‐Chao
Published: December 2014

A novel BODIPY‐based fluorescent thermometer, which shows a lysosome‐targeting property, was successfully prepared. Due to the electron‐donating ability of the oligo(ethylene glycols), the photoinduced electron‐transfer pathway from morpholine to BODIPY dye is blocked. The fluorescence of the thermometer quenched by intramolecular rotation at room temperature was progressively enhanced during heating due to the increased microviscosity around the fluorophore.
Mechanistic Aspects of the Gas‐Phase Reactions of Halobenzenes with Bare Lanthanide Cations: A Combined Experimental/Theoretical Investigation
Authors: Zhou Shaodong , Schlangen Maria , Schwarz Helmut
Published: December 2014

The gas‐phase reactions of chlorobenzene with all atomic lanthanide cations Ln+ (except Pm+) have been investigated by using Fourier transform ion cyclotron resonance mass spectrometry in conjunction with density functional theory calculations. According to the latter, a direct chlorine transfer to the lanthanide cation, which has been observed previously for fluorine abstraction from fluorobenzene, is not operative for the C6H5Cl/Ln+ couples; rather, chlorine transfer proceeds through an initial coordination of the lanthanide cation to the aromatic ring of the substrate. Both, the product distribution and the chlorine abstraction efficiencies are affected by the bond dissociation energy (BDE(Ln+Cl)) as well as the promotion energies of Ln+ to attain a 4fn 5d1 6s1 configuration. In addition, mechanistic aspects of some CH and CC bond activations are presented. Where appropriate, comparison with the previously studied C6H5F/Ln+ systems is made.
New Atropisomeric Amino Alcohol Ligands for Enantioselective Addition of Diethylzinc to Aldehydes
Authors: Faigl F. , Deák SZ. , Erdélyi ZS. , Holczbauer T. , Czugler M. , Nyerges M. , Mátravölgyi B.
Published: December 2014

Efficient synthesis of several new atropisomeric amino alcohols having 1‐phenyl‐1H‐pyrrole skeleton are reported. Steric arrangements of the products were confirmed by a single‐crystal X‐ray measurement. The consequences of the size of the N‐substituents on enantioinduction were examined by employing the enantioselective catalytic addition of diethylzinc to a series of substituted benzaldehydes (yields 91–97%, up to 85% enantiomeric excess). The special effect of the ortho methoxy group of the substrate on the enantioinduction is also interpreted. Chirality 27:216–222, 2015. © 2014 Wiley Periodicals, Inc.
Detection of Xeljanz Enantiomers in Diethyl Amine Active Pharmaceutical Ingredients and Tablets
Authors: Wang Na‐Na , Zhang Dao‐Lin , Jiang Xin‐Hui
Published: December 2014

A high‐performance liquid chromatography (HPLC) method was established to detect Xeljanz enantiomers in active pharmaceutical ingredients (APIs) and tablets. The separation was achieved on a Chiralpak IC column using a mobile phase of hexane‐ethanol‐diethylamine (65:35:0.1, v/v). The detection wavelength was 289 nm. The peak areas and the enantiomer concentrations in the range of 0.15–2.25 μg•mL−1 were in high linearity, with correlation coefficients higher than 0.999. The recoveries were 86.44% at the concentrations of 7.5, 18.75, and 37.5 μg•mL−1. The limit of detection (LOD) and limit of quantification (LOQ) were 0.042 and 0.14 μg•mL−1, respectively. This HPLC method is suitable for detecting the enantiomers of Xeljanz in its APIs and tablets. Chirality 27:235–238, 2015. © 2014 Wiley Periodicals, Inc.
Endothelial monolayers and transendothelial migration depend on mechanical properties of the substrate
Authors: Onken Michael D. , Mooren Olivia L. , Mukherjee Suranjana , Shahan Stefanie T. , Li Jinmei , Cooper John A.
Published: December 2014

Endothelial cells (ECs) line the microvasculature and constitute a barrier between the vessel lumen and surrounding tissues. ECs inform circulating immune cells of the health and integrity of surrounding tissues, recruiting them in response to pathogens and tissue damage. ECs play an active role in the transmigration of immune cells across the vessel wall. We have discovered important differences in the properties of ECs on soft hydrogel substrates of varying stiffness, in comparison to glass. Primary ECs from several human sources were tested; all formed monolayers normally on soft substrates. EC monolayers formed more mature cell‐cell junctions on soft substrates, relative to glass, based on increased recruitment of vinculin and F‐actin. EC monolayers supported transendothelial migration (TEM) on soft substrates. Immune cells, including peripheral blood lymphocytes (PBLs) and natural killer cells, showed decreasing numbers of paracellular (between‐cell) transmigration events with decreasing substrate stiffness, while the number of transcellular (through‐cell) events increased for PBLs. Melanoma cancer cells showed increased transmigration with decreased stiffness. Our findings demonstrate that endothelial monolayers respond to the mechanical properties of their surroundings, which can regulate the integrity and function of the monolayer independently from inflammatory signals. Soft hydrogel substrates are a more appropriate and physiological model for tissue environments than hard substrates, with important implications for the experimental analysis of TEM. © 2014 Wiley Periodicals, Inc.
Therapeutic targeting of tumor suppressor genes
Authors: Morris Luc G. T. , Chan Timothy A.
Published: December 2014

Carcinogenesis is a multistep process attributable to both gain‐of‐function mutations in oncogenes and loss‐of‐function mutations in tumor suppressor genes. Currently, most molecular targeted therapies are inhibitors of oncogenes, because inactivated tumor suppressor genes have proven harder to “drug.” Nevertheless, in cancers, tumor suppressor genes undergo alteration more frequently than do oncogenes. In recent years, several promising strategies directed at tumor suppressor genes, or the pathways controlled by these genes, have emerged. Here, we describe advances in a number of different methodologies aimed at therapeutically targeting tumors driven by inactivated tumor suppressor genes. Cancer 2015;121:1357–1368. © 2014 American Cancer Society.
Conditional survival in pediatric malignancies: Analysis of data from the Childhood Cancer Survivor Study and the Surveillance, Epidemiology, and End Results Program
Authors: Mertens Ann C. , Yong Jian , Dietz Andrew C. , Kreiter Erin , Yasui Yutaka , Bleyer Archie , Armstrong Gregory T. , Robison Leslie L. , Wasilewski‐Masker Karen
Published: December 2014

BACKGROUND

Long‐term survivors of pediatric cancer are at risk of life‐threatening late effects of their cancer. Previous studies have shown excesses in long‐term mortality within high‐risk groups defined by demographic and treatment characteristics.

METHODS

To investigate conditional survival in a pediatric cancer population, the authors performed an analysis of conditional survival in the original Childhood Cancer Survivor Study (CCSS) cohort and the Surveillance, Epidemiology, and End Results (SEER) database registry. The overall probability of death for patients at 5 years and 10 years after they survived 5, 10, 15, and 20 years since cancer diagnosis and cause‐specific death in 10 years for 5‐year survivors were estimated using the cumulative incidence method.

RESULTS

Among patients in the CCSS and SEER cohorts who were alive 5 years after their cancer diagnosis, within each diagnosis group at least 92% were alive in the subsequent 5 years, except for patients with leukemia, of whom only 88% of 5‐year survivors remained alive in the subsequent 5 years. The probability of all‐cause mortality in the next 10 years among patients who survived at least 5 years after diagnosis was 8.8% in CCSS and 10.6% in SEER, approximately 75% of which was due to neoplasms as the cause of death.

CONCLUSIONS

The risk of death among survivors of pediatric cancer in 10 years can vary between diagnosis groups by at most 12%, even up to 20 years after diagnosis. This information is clinically significant when counseling patients regarding their conditional survival, particularly when survivors are seen in long‐term follow‐up. Cancer 2015;121:1108–1117. © 2014 American Cancer Society.
Prevalence of somatic mutl homolog 1 promoter hypermethylation in Lynch syndrome colorectal cancer
Authors: Moreira Leticia , Muñoz Jenifer , Cuatrecasas Míriam , Quintanilla Isabel , Leoz Maria Liz , Carballal Sabela , Ocaña Teresa , López‐Cerón María , Pellise Maria , Castellví‐Bel Sergi , Jover Rodrigo , Andreu Montserrat , Carracedo Angel , Xicola Rosa Maria , Llor Xavier , Boland Clement Richard , Goel Ajay , Castells Antoni , Balaguer Francesc
Published: December 2014

BACKGROUND

Colorectal cancers (CRCs) that have microsatellite instability (MSI) and mutL homolog 1 (MLH1) immunoloss are observed in 3 clinical scenarios: Lynch syndrome (LS), sporadic MSI CRC, and Lynch‐like syndrome (LLS). v‐Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational analysis is used to differentiate LS from sporadic MSI CRC. The role of MLH1 promoter methylation status for the differential diagnosis of these clinical forms is not well established. The objectives of this study were: 1) to analyze MLH1 promoter methylation in MLH1‐deficient CRCs by pyrosequencing, and 2) to assess its role in the differential diagnosis of MLH1‐deficient CRCs.

METHODS

In total, 165 CRCs were analyzed, including LS (n = 19), MSI BRAF‐mutated CRC (n = 37), MSI BRAF wild‐type CRC (n = 60), and a control group of CRCs without MSI (microsatellite stable [MSS] CRC; n = 49). MLH1 promoter methylation status was analyzed by pyrosequencing, and the ability of different strategies to identify LS was assessed.

RESULTS

The average ± standard deviation methylation in LS (9% ± 7%) was significantly lower than that in MSI BRAF‐mutated CRC (42% ± 17%; P < .001) and in MSI BRAF wild‐type CRC (25% ± 19%; P = .002). Somatic MLH1 hypermethylation was detected in 3 patients (15.8%) with LS, in 34 patients (91.9%) with MSI BRAF‐mutated CRC, and in 37 patients (61.7%) with MSI BRAF wild‐type tumors. Patients with MSI BRAF wild‐type, unmethylated tumors (ie, LLS) had a stronger family history of CRC than those who had tumors with MLH1 methylation (P < .05). The sensitivity for ruling out LS was 100% for BRAF analysis, 84.2% for MLH1 methylation analysis, and 84.2% for the combination of both analyses.

CONCLUSIONS

Somatic MLH1 promoter methylation occurs in up to 15% of LS CRCs. Somatic BRAF analysis is the most sensitive strategy for ruling out LS. Patients who have CRCs with loss of MLH1 protein expression and neither BRAF mutation nor MLH1 methylation resemble patients with LS. Cancer 2015;121:1395–1404. © 2014 American Cancer Society.
Improving our understanding of the use of traditional complementary/alternative medicine in children with cancer
Authors: Ladas Elena J. , Lin Meiko , Antillion Federico , Rivas Silvia , Chantada Guillermo , Cacciavillano Walter , Ortiz Roberta , Stein Katja , Castillo Luis , Rocha Valeria , Fu Ligia , Rodriquez Hilze , Kelly Kara M.
Published: December 2014

BACKGROUND

Children with cancer in high‐income and low‐income countries often use traditional complementary/alternative medicine (TCAM). With efforts by the World Health Organization and international twinning programs improving access to conventional care for patients with childhood cancer, understanding the global use of TCAM is important because reliance on TCAM may affect time to presentation, adherence, and abandonment of care. In the current study, the authors describe the process and validation of an international survey documenting the use of TCAM among children with cancer.

METHODS

The survey was designed to collect information on TCAM use and associated factors through both open‐ended and close‐ended questions. During the period between June 2012 and December 2013, the survey was administered to 300 children and adolescents (or their parents) who were undergoing treatment for cancer at a collaborating institution located in Mexico, Uruguay, and Nicaragua.

RESULTS

For the majority of constructs, the survey demonstrated strong test‐retest reliability as evidenced by an intraclass correlation of at least ≥0.79 in each of the participating countries. The survey demonstrated good internal consistency and reliability across countries (α range from. 77 to. 85 for the belief scale; and an α range from. 60 to. 86 for the cause scale) and convergent validity between TCAM beliefs and behavior constructs (adjusted correlation range, 0.35‐0.60).

CONCLUSIONS

The results of the current study demonstrate the successful development of a cross‐cultural survey that produced results that were reliable and valid. These findings will aid investigators in providing guidelines concerning TCAM, support the development of education and research priorities, and identify variables associated with TCAM that are region‐specific. Cancer 2015;121:1492–1498. © 2014 American Cancer Society.
Does phase 1 trial enrollment preclude quality end‐of‐life care? Phase 1 trial enrollment and end‐of‐life care characteristics in children with cancer
Authors: Levine Deena R. , Johnson Liza‐Marie , Mandrell Belinda N. , Yang Jie , West Nancy K. , Hinds Pamela S. , Baker Justin N.
Published: December 2014

BACKGROUND

End‐of‐life care (EOLC) discussions and treatment‐related decisions, including phase 1 trial enrollment, in patients with incurable disease are complex and can influence the quality of EOLC received. The current study was conducted in pediatric oncology patients to determine whether end‐of‐life characteristics differed between those who were and were not enrolled in a phase 1 trial.

METHODS

The authors reviewed the medical records of 380 pediatric oncology patients (aged <22 years at the time of death) who died during a 3.5‐year period. Of these, 103 patients with hematologic malignancies were excluded. A total of 277 patients with a diagnosis of a brain tumor or other solid tumor malignancy were divided into 2 groups based on phase 1 trial enrollment: a phase 1 cohort (PIC; 120 patients) and a non‐phase 1 cohort (NPIC; 157 patients). The EOLC characteristics of these 2 cohorts were compared using regression analysis and chi‐square testing.

RESULTS

A comparison of patients in the PIC and NPIC revealed no significant differences in either demographic characteristics (including sex, race, religious affiliation, referral origin, diagnosis, or age at diagnosis, with the exception of age at the time of death [P =.03]) or in EOLC indices (such as use or timing of do not attempt resuscitation orders, hospice use or length of stay, forgoing life‐sustaining therapies, location of death, time from first EOLC discussion to death, and total number of EOLC discussions).

CONCLUSIONS

The results of the current study of a large cohort of deceased pediatric cancer patients indicate that enrollment on a phase 1 trial does not affect EOLC characteristics, suggesting that quality EOLC can be delivered regardless of phase 1 trial participation. Cancer 2015;121:1508–1512. © 2014 American Cancer Society.
Bevacizumab‐induced hypertension is a predictive marker for improved outcomes in patients with recurrent glioblastoma treated with bevacizumab
Authors: Zhong Jim , Ali Arif N. , Voloschin Alfredo D. , Liu Yuan , Curran Walter J. , Crocker Ian R. , Shu Hui‐Kuo G.
Published: December 2014

BACKGROUND

Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor and is approved for the treatment of patients with recurrent glioblastoma (GBM). Previous authors have reported differential response to bevacizumab on an individual basis. Bevacizumab‐induced hypertension is a well‐documented side effect, and some reports have suggested this occurrence to be related to treatment outcome in other cancers. In the current study, the authors analyzed patients with recurrent GBM who were treated with bevacizumab based on whether the patients developed drug‐induced hypertension.

METHODS

All patients with GBM treated within the Emory Healthcare system from 2007 through 2012 were reviewed. A total of 82 patients were identified who received bevacizumab for the treatment of recurrent GBM and were included in the current study. Patients were classified as normotensive or hypertensive depending on whether hypertension developed that was attributable to therapy. Progression‐free survival (PFS) and overall survival (OS) were graphed by the Kaplan‐Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards method.

RESULTS

The median follow‐up was 19.7 months. Of the 82 patients with recurrent GBM who were treated with bevacizumab, 30 developed drug‐induced hypertension. The median time to the development of hypertension was 21 days. The median PFS for the normotensive and hypertensive groups were 2.5 months (95% confidence interval [95% CI], 1.6‐3.0 months) and 6.7 months (95% CI, 4.6‐10.0 months), respectively (P<.001). The median OS times for the normotensive and hypertensive groups were 4.9 months (95% CI, 4.4‐6.8 months) and 11.7 months (95% CI, 9.0‐20.5 months), respectively (P<.001).

CONCLUSIONS

Patients with recurrent GBM who developed bevacizumab‐induced hypertension demonstrated significantly better PFS and OS compared with normotensive individuals. Bevacizumab‐induced hypertension may be a physiologic marker of outcome in patients with recurrent GBM. Cancer 2015;121:1456–1462. © 2014 American Cancer Society.