bluuebunny/crossref_metadata_2025 huggingface dataset:
Die Struktur eines transienten Komplexes einer nicht‐ribosomalen Peptidsynthetase mit einer P450‐Monooxygenase
Authors: Haslinger Kristina , Brieke Clara , Uhlmann Stefanie , Sieverling Lina , Süssmuth Roderich D. , Cryle Max J.
Published: July 2014

Untersuchungen zum Verständnis des Wechselspiels von nicht‐ribosomalen Peptidsynthethasen (NRPS), einer wichtigen Quelle für Sekundärmetaboliten, mit modifizierenden Enzymen stellen eine große Herausforderung dar, da diese Interaktionen oft von transienter Natur sind. Mithilfe einer Reihe von synthetischen inhibitorartigen Verbindungen gelang es, einen stabilisierten Komplex eines solchen modifizierenden Enzyms mit einer NRPS‐Domäne zu bilden und strukturell zu charakterisieren. Es handelt sich um eine Peptidyl‐Carrier‐Protein(PCP)‐Domäne der NRPS gebunden an ein Cytochrom‐P450‐Enzym, das essentiell für die Bereitstellung von β‐hydroxylierten Aminosäurevorläufern in der Biosynthese des cyclischen Depsipeptids Skyllamycin ist. Die Struktur zeigt, dass die Komplexbildung vorwiegend auf hydrophoben Wechselwirkungen beruht, deren Auftreten durch geringfügige Änderungen in der PCP‐Struktur kontrolliert wird, und somit Selektivität gegenüber strukturell sehr ähnlichen PCP‐Domänen vermittelt.
Selective Ortho‐Hydroxylation–Defluorination of 2‐Fluorophenolates with a Bis(μ‐oxo)dicopper(III) Species
Authors: Serrano‐Plana Joan , Garcia‐Bosch Isaac , Miyake Ryosuke , Costas Miquel , Company Anna
Published: July 2014

The bis(μ‐oxo)dicopper(III) species [CuIII2(μ‐O)2(m‐XYLMeAN)]2+ (1) promotes the electrophilic ortho‐hydroxylation–defluorination of 2‐fluorophenolates to give the corresponding catechols, a reaction that is not accomplishable with a (η2:η2‐O2)dicopper(II) complex. Isotopic labeling studies show that the incoming oxygen atom originates from the bis(μ‐oxo) unit. Ortho‐hydroxylation–defluorination occurs selectively in intramolecular competition with other ortho‐substituents such as chlorine or bromine.
The IX (X=O,N,C) Double Bond in Hypervalent Iodine Compounds: Is it Real?
Authors: Ivanov Alexander S. , Popov Ivan A. , Boldyrev Alexander I. , Zhdankin Viktor V.
Published: July 2014

IX (X=O, N, C) bonding was analyzed in the related hypervalent iodine compounds based on the adaptive natural density partitioning (AdNDP) approach. The results confirm the presence of a I→X σ dative bond, as opposed to the widely used IX notation. A clear formulation of the electronic structure of these hypervalent iodine compounds would be useful in establishing reaction mechanisms and electronic structures in bioinorganic problems of general applicability.
Analysis of Diazofluorene DNA Binding and Damaging Activity: DNA Cleavage by a Synthetic Monomeric Diazofluorene
Authors: Woo Christina M. , Ranjan Nihar , Arya Dev P. , Herzon Seth B.
Published: July 2014

The lomaiviticins and kinamycins are complex DNA damaging natural products that contain a diazofluorene functional group. Herein, we elucidate the influence of skeleton structure, ring and chain isomerization, D‐ring oxidation state, and naphthoquinone substitution on DNA binding and damaging activity. We show that the electrophilicity of the diazofluorene appears to be a significant determinant of DNA damaging activity. These studies identify the monomeric diazofluorene 11 as a potent DNA cleavage agent in tissue culture. The simpler structure of 11 relative to the natural products establishes it as a useful lead for translational studies.
Chlorine‐Free Pyrotechnics: Copper(I) Iodide as a “Green” Blue‐Light Emitter
Authors: Klapötke Thomas M. , Rusan Magdalena , Sabatini Jesse J.
Published: July 2014

The generation of blue‐light‐emitting pyrotechnic formulations without the use of chlorine‐containing compounds is reported. Suitable blue‐light emission has been achieved through the generation of molecular emitting copper(I) iodide. The most optimal copper(I) iodide based blue‐light‐emitting formulation was found to have performances exceeding those of chlorine‐containing compositions, and was found to be insensitive to various ignition stimuli.
Intumescent flame retardant polyurethane/starch composites: Thermal, mechanical, and rheological properties
Authors: Gavgani Jaber Nasrollah , Adelnia Hossein , Mir Mohamad Sadeghi Gity , Zafari Farhad
Published: July 2014

Intumescent flame retardant polyurethane/starch (IFRPU/starch) composites were prepared by means of melt blending. Microencapsulated ammonium polyphosphate (MCAPP) was added to improve its compatibility with matrix, retardation of reaction between acid and carbon source, and its water resistancy. Fourier transform infrared spectroscopy (FTIR) confirmed the presence of hydrogen bonding and entangled network between IFR system and PU matrix. Further, scanning electron microscopy (SEM) illustrated homogeneity of starch in matrix. By addition of 10 wt % of starch and 20 wt % of IFR, limiting oxygen index (LOI) increased from 22.0 to 40.0 and UL94 V0 rating was achieved. Differential scanning calorimetry (DSC) detected three endothermic transitions and one glass transition (Tg). The temperature of transition III and Tg increased with starch due to crosslinking between PU and starch. The improved thermal stability in the presence of starch was confirmed by thermogravimetric analysis (TGA). Beside the fact that starch was used as a carbonization agent to improve flame retardancy, it also effectively led to enhanced mechanical and viscoelastic properties. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41158.
Electrical insulation characteristics of alumina, titania, and organoclay nanoparticles filled PP/EPDM nanocomposites
Authors: Hamzah Muhammad Safwan , Jaafar Mariatti , Mohd Jamil Mohamad Kamarol
Published: July 2014

In this study, nanofillers composed of alumina, titania, and organoclay were separately embedded in 50% polypropylene (PP) and 50% ethylene propylene diene monomer (EPDM) blends. Several formulations of PP/EPDM nanocomposites were prepared using an internal mixer and were molded using a compression mold to produce test samples. The effects of filler loading (2, 4, 6, and 8 vol %) on the dielectric breakdown strength, dielectric properties, hydrophobicity, and flammability were determined. The addition of nanofillers improved the breakdown strength (up to 2 vol %) and increased the dielectric constant and dielectric loss of the PP/EPDM nanocomposites. The hydrophobicity of PP/EPDM/Al2O3 increased, whereas the hydrophilicity of PP/EPDM/TiO2 and PP/EPDM/organoclay increased. Flammability test results showed that PP/EPDM/TiO2 had a lower burning rate than PP/EPDM/Al2O3 and PP/EPDM/organoclay. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41184.
Integrating anatomy training into radiation oncology residency: Considerations for developing a multidisciplinary, interactive learning module for adult learners
Authors: Labranche Leah , Johnson Marjorie , Palma David , D'Souza Leah , Jaswal Jasbir
Published: July 2014

Radiation oncologists require an in‐depth understanding of anatomical relationships for modern clinical practice, although most do not receive formal anatomy training during residency. To fulfill the need for instruction in relevant anatomy, a series of four multidisciplinary, interactive learning modules were developed for a cohort of radiation oncology and medical physics residents. Instructional design was based on established learning theories, with the intent of integrating knowledge of specific anatomical regions with radiology and radiation oncology practice. Each session included presentations by a radiologist and a radiation oncologist, as well as hands‐on exploration of anatomical specimens with guidance from anatomists. Pre‐ and post‐tests distributed during each session showed significant short‐term knowledge retention. According to qualitative surveys and exit interviews, participants felt more comfort’ with delineating structures, gross anatomy, and radiograph interpretation at the end of each session. Overall participant experience was positive, and the modules were considered effective for learning radiologic anatomy. Suggestions for future interventions include more time, increased clinical application, additional contouring practice and feedback, and improved coordination between each of the three disciplines. Results and conclusions from this study will be used to inform the design of a future multi‐day national workshop for Canadian radiation oncology residents. Anat Sci Educ 8: 158–165. © 2014 American Association of Anatomists.
Modeling enzymatic hydrolysis of lignocellulosic substrates using fluorescent confocal microscopy II: Pretreated biomass
Authors: Luterbacher Jeremy S. , Moran‐Mirabal Jose M. , Burkholder Eric W. , Walker Larry P.
Published: July 2014

In this study, we extend imaging and modeling work that was done in Part I of this report for a pure cellulose substrate (filter paper) to more industrially relevant substrates (untreated and pretreated hardwood and switchgrass). Using confocal fluorescence microscopy, we are able to track both the structure of the biomass particle via its autofluorescence, and bound enzyme from a commercial cellulase cocktail supplemented with a small fraction of fluorescently labeled Trichoderma reseii Cel7A. Imaging was performed throughout hydrolysis at temperatures relevant to industrial processing (50°C). Enzyme bound predominantly to areas with low autofluorescence, where structure loss and lignin removal had occurred during pretreatment; this confirms the importance of these processes for successful hydrolysis. The overall shape of both untreated and pretreated hardwood and switchgrass particles showed little change during enzymatic hydrolysis beyond a drop in autofluorescence intensity. The permanence of shape along with a relatively constant bound enzyme signal throughout hydrolysis was similar to observations previously made for filter paper, and was consistent with a modeling geometry of a hollowing out cylinder with widening pores represented as infinite slits. Modeling estimates of available surface areas for pretreated biomass were consistent with previously reported experimental results. Biotechnol. Bioeng. 2015;112: 32–42. © 2014 Wiley Periodicals, Inc.
Modeling enzymatic hydrolysis of lignocellulosic substrates using confocal fluorescence microscopy I: Filter paper cellulose
Authors: Luterbacher Jeremy S. , Moran‐Mirabal Jose M. , Burkholder Eric W. , Walker Larry P.
Published: July 2014

Enzymatic hydrolysis is one of the critical steps in depolymerizing lignocellulosic biomass into fermentable sugars for further upgrading into fuels and/or chemicals. However, many studies still rely on empirical trends to optimize enzymatic reactions. An improved understanding of enzymatic hydrolysis could allow research efforts to follow a rational design guided by an appropriate theoretical framework. In this study, we present a method to image cellulosic substrates with complex three‐dimensional structure, such as filter paper, undergoing hydrolysis under conditions relevant to industrial saccharification processes (i.e., temperature of 50°C, using commercial cellulolytic cocktails). Fluorescence intensities resulting from confocal images were used to estimate parameters for a diffusion and reaction model. Furthermore, the observation of a relatively constant bound enzyme fluorescence signal throughout hydrolysis supported our modeling assumption regarding the structure of biomass during hydrolysis. The observed behavior suggests that pore evolution can be modeled as widening of infinitely long slits. The resulting model accurately predicts the concentrations of soluble carbohydrates obtained from independent saccharification experiments conducted in bulk, demonstrating its relevance to biomass conversion work. Biotechnol. Bioeng. 2015;112: 21–31. © 2014 Wiley Periodicals, Inc.
Modeling the nutrient removal process in aerobic granular sludge system by coupling the reactor‐ and granule‐scale models
Authors: Kagawa Y. , Tahata J. , Kishida N. , Matsumoto S. , Picioreanu C. , van Loosdrecht M.C.M. , Tsuneda S.
Published: July 2014

We developed a model for nutrient removal in an aerobic granular sludge system. This model can quantitatively describe the start‐up of the system by coupling a model for studying the population dynamics of the granules in the reactor (reactor‐scale model) and a model for studying the microbial community structure in the granules (granule‐scale model). The reactor‐scale model is used for simulation for 10 days from the start, during which the granule size is relatively small; the granule‐scale model is used after Day 10. The present approach proposes the output data of the reactor‐scale model after 10 days as initial conditions for the granule‐scale model. The constructed model satisfactorily describes experimental data in various spatial and temporal scales, which were obtained in this study by performing the anaerobic–aerobic–anoxic cycles using a sequencing batch reactor. Simulations using this model quantitatively predicted that the stability of nutrient removal process depended largely on the dissolved oxygen (DO) concentration, and the DO setpoint adaptation could improve the nutrient removal performance. Biotechnol. Bioeng. 2015;112: 53–64. © 2014 Wiley Periodicals, Inc.
Use of a small molecule cell cycle inhibitor to control cell growth and improve specific productivity and product quality of recombinant proteins in CHO cell cultures
Authors: Du Zhimei , Treiber David , McCarter John D. , Fomina‐Yadlin Dina , Saleem Ramsey A. , McCoy Rebecca E. , Zhang Yuling , Tharmalingam Tharmala , Leith Matthew , Follstad Brian D. , Dell Brad , Grisim Brent , Zupke Craig , Heath Carole , Morris Arvia E. , Reddy Pranhitha
Published: July 2014

The continued need to improve therapeutic recombinant protein productivity has led to ongoing assessment of appropriate strategies in the biopharmaceutical industry to establish robust processes with optimized critical variables, that is, viable cell density (VCD) and specific productivity (product per cell, qP). Even though high VCD is a positive factor for titer, uncontrolled proliferation beyond a certain cell mass is also undesirable. To enable efficient process development to achieve consistent and predictable growth arrest while maintaining VCD, as well as improving qP, without negative impacts on product quality from clone to clone, we identified an approach that directly targets the cell cycle G1‐checkpoint by selectively inhibiting the function of cyclin dependent kinases (CDK) 4/6 with a small molecule compound. Results from studies on multiple recombinant Chinese hamster ovary (CHO) cell lines demonstrate that the selective inhibitor can mediate a complete and sustained G0/G1 arrest without impacting G2/M phase. Cell proliferation is consistently and rapidly controlled in all recombinant cell lines at one concentration of this inhibitor throughout the production processes with specific productivities increased up to 110 pg/cell/day. Additionally, the product quality attributes of the mAb, with regard to high molecular weight (HMW) and glycan profile, are not negatively impacted. In fact, high mannose is decreased after treatment, which is in contrast to other established growth control methods such as reducing culture temperature. Microarray analysis showed major differences in expression of regulatory genes of the glycosylation and cell cycle signaling pathways between these different growth control methods. Overall, our observations showed that cell cycle arrest by directly targeting CDK4/6 using selective inhibitor compound can be utilized consistently and rapidly to optimize process parameters, such as cell growth, qP, and glycosylation profile in recombinant antibody production cultures. Biotechnol. Bioeng. 2015;112: 141–155. © 2014 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
Effect of temperature change on anammox activity
Authors: Lotti T. , Kleerebezem R. , van Loosdrecht M.C.M.
Published: July 2014

Autotrophic nitrogen removal appears as a prerequisite for the implementation of energy autarchic municipal wastewater treatment plants. Whilst the application of anammox‐related technologies in the side‐stream is at present state of the art, the feasibility of this energy‐efficient process in main‐stream conditions is still under investigation. Lower operating temperatures and ammonium concentrations, together with a demand for high and stable nitrogen removal efficiency, represent the main challenges to overcome for this appealing new frontier of the wastewater treatment field. In this study, we report the short‐term effect of temperature on the maximum biomass specific activity of anaerobic ammonium oxidizing (anammox) bacteria as evaluated by means of batch tests. The experiments were performed on anammox biomass sampled from two full‐scale reactors and two lab‐scale reactors, all characterized by different reactor configurations and operating conditions. The results indicate that for the anammox conversion, the temperature dependency cannot be accurately modeled by one single Arrhenius coefficient (i.e., θ) as typically applied for other biological processes. The temperature effect is increasing at lower temperatures. Adaptation of anammox bacteria after long‐term cultivation at 20 and 10°C was observed. Implications for modeling and process design are finally discussed. Biotechnol. Bioeng. 2015;112: 98–103. © 2014 Wiley Periodicals, Inc.
A novel nonpharmacologic technique to remove entrapped radial sheath
Authors: Pancholy Samir B. , Karuparthi Poorna Rajasekhar , Gulati Rajiv
Published: July 2014

Radial artery access for performance of coronary and peripheral diagnostic as well as interventional procedures is on the rise. With increasing adoption comes the expected increase in procedural complications. We describe a novel, simple, and effective nonpharmacologic solution for sheath entrapment related to pharmaco‐resistant radial artery spasm. © 2014 Wiley Periodicals, Inc.
Mathematical Modeling of Chiral Symmetry Breaking due to Differences in Crystal Growth Kinetics
Authors: Suwannasang Kittisak , Coquerel Gerard , Rougeot Celine , Flood Adrian E.
Published: July 2014

Two simple models are proposed and tested for the mechanism of ripening of a conglomerate suspension to a single enantiomorph by temperature cycles. In both models, the initial crystal size distributions and masses of the two enantiomorphs are equal, but either the crystal growth rate or the growth rate distribution is varied. The difference in the crystal growth kinetics of the two enantiomorphs may be caused by the intrinsic thermodynamic stability of the crystals occurring in the initial suspension. The initial nucleation of one of the two enantiomers will occur earlier than that of the counter‐enantiomer. This results in the formation of two populations occurring under different conditions, leading to different internal crystalline perfection and therefore different thermodynamic stability.
Spherulitic Growth of Gold Particles Precipitated from Aqueous Solution
Authors: Wang Lijuan , Andreassen Jens‐Petter
Published: July 2014

Spherical gold particles were formed by reduction of auric acid with ascorbic acid in both spontaneous precipitation and seeded experiments. Micron‐sized gold polycrystalline sea urchin‐like particles were generated at lower pH conditions with and without a polymeric stabilizer. The fact that growth was depending on the surface area of the seeds and at the same time was not significantly affected by stabilizing polymers illustrates that the underlying particle enlargement mechanism is crystal growth and not an assembly of already nucleated nano‐crystals by aggregation as usually claimed in the literature. When the seed surface area was reduced, nucleation of new gold nanoparticles was observed, and these particles did not show any tendency to aggregate. Based on this understanding it was demonstrated how the morphology of the micron‐sized particles can be controlled.
Novel Transition‐Metal (M=Cr, Mo, W, Fe) Carbonyl Complexes with Bis(guanidinato)silicon(II) Ligands
Authors: Mück Felix M. , Kloß Dorit , Baus Johannes A. , Burschka Christian , Tacke Reinhold
Published: July 2014

The donor‐stabilized silylene 2 (the first bis(guanidinato)silicon(II) complex) reacts with the transition‐metal carbonyl complexes [M(CO)6] (M=Cr, Mo, W) to form the respective silylene complexes 7–10. In the reactions with [M(CO)6] (M=Cr, Mo, W), the bis(guanidinato)silicon(II) complex 2 behaves totally different compared with the analogous bis(amidinato)silicon(II) complex 1, which reacts with [M(CO)6] as a nucleophile to replace only one of the six carbonyl groups. In contrast, the reaction of 2 leads to the novel spirocyclic compounds 7–9 that contain a four‐membered SiN2C ring and a five‐membered MSiN2C ring with a MSi and MN bond (nucleophilic substitution of two carbonyl groups). Compounds 7–10 were characterized by elemental analyses (C, H, N), crystal structure analyses, and NMR spectroscopic studies in the solid state and in solution.
Spontaneous Stepwise Self‐Assembly of a Polyoxometalate–Organic Hybrid into Catalytically Active One‐Dimensional Anisotropic Structures
Authors: Yin Panchao , Bayaguud Aruuhan , Cheng Peng , Haso Fadi , Hu Lang , Wang Joy , Vezenov Dmitri , Winans Randall E. , Hao Jian , Li Tao , Wei Yongge , Liu Tianbo
Published: July 2014

An inorganic–organic hybrid surfactant with a hexavanadate cluster as the polar head group was designed and observed to assemble into micelle structures, which further spontaneously coagulate into a 1D anisotropic structure in aqueous solutions. Such a hierarchical self‐assembly process is driven by the cooperation of varied noncovalent interactions, including hydrophobic, electrostatic, and hydrogen‐bonding interactions. The hydrophobic interaction drives the quick formation of the micelle structure; electrostatic interactions involving counterions leads to the further coagulation of the micelles into larger assemblies. This process is similar to the crystallization process, but the specific counterions and the directional hydrogen bonding lead to the 1D growth of the final assemblies. Since most of the hexavanadates are exposed to the surface, the 1D assembly with nanoscale thickness is a highly efficient heterogeneous catalyst for the oxidation of organic sulfides with appreciable recyclability.
Thermal or Mechanical Stimuli‐Induced Photoluminescence Color Change of a Molecular Assembly Composed of an Amphiphilic Anthracene Derivative in Water
Authors: Sagara Yoshimitsu , Komatsu Toru , Terai Takuya , Ueno Tasuku , Hanaoka Kenjiro , Kato Takashi , Nagano Tetsuo
Published: July 2014

Molecular assemblies that change photoluminescence color in response to thermal or mechanical stimulation without dissociation into the monomeric states in water are described herein. A dumbbell‐shaped amphiphilic compound forms micellar molecular assemblies in water and exhibits yellow photoluminescence derived from excimer formation of the luminescent core, which contains a 2,6‐diethynylanthracene moiety. Annealing of the aqueous solution induces a photoluminescence color change from yellow to green (λem, max=558→525 nm). The same photoluminescence color change is also achieved by rubbing the yellow‐photoluminescence‐emitting molecular assemblies adsorbed on glass substrates with cotton wool in water. The observed green photoluminescence is ascribed to micelles that are distinct from the yellow‐photoluminescence‐emitting micelles, on the basis of transmission electron microscopy observations, atomic force microscopy observations, and dynamic light scattering measurements. We examined the relationship between the structure of the molecular assemblies and the photophysical properties of the anthracene derivative in water before and after thermal or mechanical stimulation and concluded that thermal or mechanical stimuli‐induced slight changes of the molecular‐assembled structures in the micelles result in the change in the photoluminescence color from yellow to green in water.
Peptides Come Round: Using SICLOPPS Libraries for Early Stage Drug Discovery
Authors: Lennard Katherine R. , Tavassoli Ali
Published: July 2014

Cyclic peptides are an emerging class of molecular therapeutics that are increasingly viewed as ideal backbones for modulation of protein–protein interactions. A split‐intein based method, termed SICLOPPS, enables the rapid generation of genetically encoded cyclic peptide libraries of around a hundred million members. Here we review recent approaches using SICLOPPS for the discovery of bioactive compounds.
Synthesis of Prenyl‐ and Geranyl‐Substituted Carbazole Alkaloids by DIBAL‐H Promoted Reductive Pyran Ring Opening of Dialkylpyrano[3,2‐a]carbazoles
Authors: Hesse Ronny , Kataeva Olga , Schmidt Arndt W. , Knölker Hans‐Joachim
Published: July 2014

The DIBAL‐H promoted reductive pyran ring opening of dialkylpyrano[3,2‐a]carbazoles provides a direct access to a broad range of prenyl‐ and geranyl‐substituted carbazoles. Formation of a pyran ring followed by reductive ring opening represents a new method for the introduction of prenyl and geranyl groups. In the course of the present work, we achieved the first total syntheses of the following eight carbazole alkaloids: clauraila‐E, 7‐hydroxyheptaphylline, 7‐methoxyheptaphylline, mukoenine‐B (clausenatine‐A), mukoenine‐A (girinimbilol), mahanimbinol (mahanimbilol), euchrestine‐A, and isomurrayafoline‐B.
Ionische Flüssigkeiten im Schulunterricht
Authors: Pellowska Maren , Handel Robyn , Bader Hans Joachim , Flint Alfred
Published: July 2014

Ionische Verbindungen, die unter 100 °C schmelzen, werden Ionische Flüssigkeiten genannt. Diesen Verbindungen kommt seit einigen Jahren wegen ihrer Eigenschaften als Lösungsmittel oder Reaktionsmedien eine stetig steigende Bedeutung zu. In diesem Beitrag werden Aufbau und Eigenschaften Ionischer Flüssigkeiten dargestellt sowie Vorschläge für einführende Experimente gegeben.
Substance use disorder and its effects on outcomes in men with advanced‐stage prostate cancer
Authors: Chhatre Sumedha , Metzger David S. , Malkowicz S. Bruce , Woody George , Jayadevappa Ravishankar
Published: July 2014

BACKGROUND

Substance use disorder in patients with cancer has implications for outcomes. The objective of this study was to analyze the effects of the type and timing of substance use on outcomes in elderly Medicare recipients with advanced prostate cancer.

METHODS

This was an observational cohort study using Surveillance, Epidemiology, and End Results (SEER)‐Medicare linked data from 2000 to 2009. Among men who were diagnosed with advanced prostate cancer between 2001 and 2004, we identified those who had a claim for substance use disorder in the year before cancer diagnosis, 1 year after cancer diagnosis, and an additional 4 years after diagnosis. The outcomes investigated were use of health services, costs, and mortality.

RESULTS

The prevalence of substance use disorder was 10.6%. The category drug psychoses and related had greater odds of inpatient hospitalizations (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9‐2.8), outpatient hospital visits (OR, 2.6; 95% CI, 1.9‐3.6), and emergency room visits (OR, 1.7; 95% CI, 1.2‐2.4). Substance use disorder in the follow‐up phase was associated with greater odds of inpatient hospitalizations (OR, 2.0; 95% CI, 1.8‐2.2), outpatient hospital visits (OR, 2.0; 95% CI, 1.7‐2.4), and emergency room visits (OR, 1.7; 95% CI, 1.5‐2.1). Compared with men who did not have substance use disorder, those in the category drug psychoses and related had 70% higher costs, and those who had substance use disorder during the follow‐up phase had 60% higher costs. The hazard of all‐cause mortality was highest for patients in the drug psychoses and related category (hazard ratio, 1.3; 95% CI, 1.1‐1.7) and the substance use disorder in treatment phase category (hazard ratio, 1.5; 95% CI, 1.3‐1.7).

CONCLUSIONS

The intersection of advanced prostate cancer and substance use disorder may adversely affect outcomes. Incorporating substance use screening and treatments into prostate cancer care guidelines and coordination of care is desirable. Cancer 2014;120:3338–3345. © 2014 American Cancer Society.
Surgery for primary hyperparathyroidism
Authors: Callender Glenda G. , Udelsman Robert
Published: July 2014

In the Western world, primary hyperparathyroidism is now a relatively common disorder that is diagnosed in 0.7% of the general population and in 2% of postmenopausal women. Although patients today typically present with less severe manifestations of disease, the evaluation and management of patients with parathyroid disease remains challenging. Primary hyperparathyroidism is a complex disease process that requires careful diagnosis and thoughtful medical and surgical management. The surgical management of patients with persistent or recurrent disease, inherited primary hyperparathyroidism syndromes, and parathyroid carcinoma is particularly challenging. High‐quality imaging and reliable intraoperative adjuncts are critical to success. Cancer 2014;120:3602–3616. © 2014 American Cancer Society.
Cytology and human papillomavirus testing on cytobrushing samples from patients with head and neck squamous cell carcinoma
Authors: Donà Maria Gabriella , Giuliani Massimo , Vocaturo Amina , Spriano Giuseppe , Pichi Barbara , Rollo Francesca , Ronchetti Livia , Covello Renato , Pescarmona Edoardo , Benevolo Maria
Published: July 2014

BACKGROUND

The increasing incidence of human papillomavirus (HPV)‐related head and neck squamous cell carcinoma (HNSCC) highlights the need for simple and effective tools to evaluate head and neck lesions and their HPV status. The main objective of the current study was to investigate the association between abnormal cytology and HPV infection, assessed on cytobrushing samples, and histologically confirmed HNSCC. Second, the authors attempted to investigate whether HPV status on cytobrushing samples reflected that of the tumoral tissue.

METHODS

A total of 164 samples from HNSCC, nonmalignant lesions, or healthy mucosae of the oral cavity and oropharynx were collected by cytobrushing in PreservCyt solution and evaluated by liquid‐based cytology and Linear Array HPV genotyping test. All the findings from the cytologic samples were compared with those from the corresponding histologic samples.

RESULTS

Patients with abnormal cytology had a significantly higher risk of having an HNSCC (odds ratio [OR], 9.18; 95% confidence inteval [95% CI], 3.27‐26.49). The association was stronger for oral cancer (OR, 10.86; 95% CI, 2.51‐51.06) than oropharyngeal cancer (OR, 8.45; 95% CI, 1.62‐49.82). HPV positivity in the oropharyngeal cytobrushing was associated with a nearly 5‐fold higher risk of having abnormal cytology (OR, 4.57; 95% CI, 1.57‐13.57) as well as histologically proven oropharyngeal cancer (OR, 5.09; 95% CI, 1.09‐31.61). Comparing the HPV status on cytologic and corresponding histologic samples from patients with HNSCC, we found that 90.4% of the cases were concordant (kappa, 0.796).

CONCLUSIONS

Abnormal brushing cytology is strongly associated with a diagnosis of HNSCC, whereas HPV positivity on cytobrushing samples is only associated with oropharyngeal cancer. HPV testing on cytobrushing samples represents a valid option for the assessment of HPV infection in patients with oropharyngeal cancer. Cancer 2014;120:3477–3484. © 2014 American Cancer Society.
A panel of protein markers for the early detection of lung cancer with bronchial brushing specimens
Authors: Liu Yi‐Zhen , Jiang Yan‐Yi , Wang Bo‐Shi , Hao Jia‐Jie , Shang Li , Zhang Tong‐Tong , Cao Jian , Xu Xin , Zhan Qi‐Min , Wang Ming‐Rong
Published: July 2014

BACKGROUND

To date, no robust biomarkers have been available in clinical practice that can provide an early diagnostic evaluation of lung cancer. The objective of this study was to identify potential biomarkers for the early detection of lung cancer using bronchial brushing specimens.

METHODS

Immunocytochemistry was used to investigate the expression of 35 proteins in 880 bronchial brushing specimens from both outpatients and inpatients who had either lung cancer or benign lung lesions. An optimal panel was identified that had high sensitivity and considerable specificity for detecting lung cancer. Associations between protein expression and clinicopathologic parameters were assessed.

RESULTS

Tumor protein 53 (TP53), TP63, Ki67, epidermal growth factor receptor (EGFR), minichromosome maintenance complex component 6 (MCM6), MCM7, uncharacterized proteins KIAA1522 and KIAA0317, and ubiquitin‐protein ligase UHR1 (ICBP90) frequently presented high expression in bronchial brushing specimens from patients who had lung cancer compared with patients who had benign lung lesions. A 6‐protein panel consisting of TP53, Ki67, MCM6, MCM7, KIAA1522, and KIAA0317 was identified as the best combination, with sensitivity of 81.1% (309 of 381 specimens) for detecting nonsmall cell lung cancer (NSCLC) and 86.8% (145 of 167 specimens) for detecting small cell lung cancer (SCLC) (specificity, 83.3%; 65 of 78 specimens). The combination of cytology and the protein panel significantly improved the sensitivity of bronchial brushing examination for detecting lung cancer (P<.00001), which increased from 49.1% to 81% in early stage NSCLC (stage I and II). In combined analyses, the protein panel was positively associated with patient sex (P=.00033), tumor type (P<.00001), tumor location (P<.00001), and lymph node metastasis (P=.028).

CONCLUSIONS

The 6‐protein panel is a potential biomarker for the early detection of lung cancer in bronchial brushings. Cancer (Cancer Cytopathol) 2014;122:833–841. © 2014 American Cancer Society.
Early, Middle, or Late Administration of Zoledronate Alleviates Spontaneous Nociceptive Behavior and Restores Functional Outcomes in a Mouse Model of CFA‐Induced Arthritis
Authors: Morado‐Urbina Carlos Eduardo , Alvarado‐Vázquez Perla Abigail , Montiel‐Ruiz Rosa Mariana , Acosta‐González Rosa Issel , Castañeda‐Corral Gabriela , Jiménez‐Andrade Juan Miguel
Published: July 2014

Preclinical Research

This study was performed to evaluate whether early, middle, or late treatment of zoledronate, an approved bisphosphonate that blocks bone resorption, can reduce nociceptive behaviors in a mouse arthritis model. Arthritis was produced by repeated intra‐articular knee injections of complete Freund's adjuvant (CFA). A dose‐response curve with zoledronate (3, 30, 100, and 300 μg/kg, i.p., day 4 to day 25, twice weekly for 3 weeks) was performed, and the most effective dose of zoledronate (100 μg/kg, i.p.) was initially administered at different times of disease progression: day 4 (early), day 15 (middle), or day 21 (late) and continued until day 25 after the first CFA injection. Flinching of the injected extremity (spontaneous nociceptive behavior), vertical rearings and horizontal activity (functional outcomes), and knee edema were assessed. Zoledronate improved both functional outcomes and reduced flinching behavior. At day 25, the effect of zoledronate on flinching behavior and vertical rearings was greater in magnitude when it was given early or middle rather than late in the treatment regimen. Chronic zoledronate did not reduce knee edema in CFA‐injected mice nor functional outcomes in naïve mice by itself. These results suggest that zoledronate may have a positive effect on arthritis‐induced nociception and functional disabilities.
Mother recognition and preference after neonatal amygdala lesions in rhesus macaques (Macaca mulatta) raised in a semi‐naturalistic environment
Authors: Goursaud Anne‐Pierre S. , Wallen Kim , Bachevalier Jocelyne
Published: July 2014

Attachment to the caregiver, typically the biological mother, is crucial to young mammals' socio‐emotional development. Although studies in nonprimate species suggest that the amygdala regulates social preference and attachment development, its role in primate filial attachment development has been little investigated and has produced mixed results. This study assessed the effects of neonatal amygdala‐ (Neo‐A, N = 16) and sham‐ (Neo‐C, N = 12) lesions on mother recognition and discrimination in macaques raised in species‐typical social groups. Neonatal amygdalectomy did not affect social discriminative abilities and mother preference at 3 and 6 months of age, strongly suggesting that the amygdala is not involved in the cognitive processes underlying the development of filial attachment at least when the amygdala damage occurred after the third to fourth weeks of age. Nevertheless, as compared to sham‐operated controls, amygdalectomized infants initiated physical contact with their mothers less frequently. The findings are discussed in relation to the known contribution of the amygdala to filial attachment in both rodents and humans. © 2014 Wiley Periodicals, Inc. Dev Psychobiol 56: 1723–1734, 2014.
Perceptual narrowing: Retrospect and prospect
Authors: Flom Ross
Published: July 2014

Research is reviewed demonstrating perceptual narrowing across a variety of domains. Research is also reviewed showing that the temporal window of perceptual narrowing can be extended and, in some cases, perceptual narrowing can be reversed. Research is also reviewed highlighting the neurophysiological correlates of perceptual narrowing as well as some of the individual neurophysiological differences associated with perceptual narrowing. Various methodological issues associated with perceptual narrowing are also discussed. The broader purpose of this paper, however, is to argue that the term perceptual narrowing fails to capture the dynamic nature of this perceptual process. Finally, it is argued that just as other concepts associated with experience and development are refined and modified as new evidence emerges, likewise we need to evaluate and refine how we conceptualize perceptual narrowing. © 2014Wiley Periodicals, Inc. Dev Psychobiol 56: 1442–1453, 2014.
Diabetes Metabolism: Research and Reviews – Chinese Diabetes Society special issue: a small but encouraging step toward the successful control of diabetes in China
Authors: Weng Jianping , Pozzilli Paolo
Published: July 2014

It is now recognised that nearly one third of all people with diabetes worldwide are Chinese and that this disease is the third leading cause of death in China. In this special issue of the journal we publish articles covering a number of clinical and experimental studies of diabetes as well as metabolic diseases in China with the aim of helping the readers to better understand the overall picture of this disease in China.
Linear Analysis of the Corticothalamic Model with Time Delay
Authors: Yamaguchi Ikuhiro , Ogawa Yutaro , Nakao Hiroya , Jimbo Yasuhiko , Kotani Kiyoshi
Published: July 2014

The corticothalamic Compact Model with time delay proposed by Kim and Robinson is analyzed focusing on the resting EEG, which can be described by the linear version of the model with white‐noise input, under the assumption of spatial homogeneity and temporal steadiness. After discussing the availability and restriction of the model by comparing to the original Pre‐Compact Model, a data analysis method for the resting EEG using the model is presented. The experimental results analyzed by the method suggest that the eye‐closed state compared to the eye‐open state would be characterized by enhanced corticothalamic feedback and depressed cortical excitation. The validity of the Reduced Equations derived in our previous paper is also investigated for the resting EEG, concluding that the Reduced Equations would be available with some restriction for the resting EEG, although the center manifold theory on which the Reduced Equations are based is justified at the edge of linear stability in principle.
Portfolio Strategy Optimizing Model for Risk Management Utilizing Evolutionary Computation
Authors: Matsumura Koki , Kakinoki Hidefumi
Published: July 2014

This paper proposes a new optimizing system for stock portfolios that uses evolutionary computation techniques to derive a highly suitable combination and investment ratio of brands as well as an appropriate trading‐strategy tree. Accurately predicting price trends in the stock market is a difficult task to achieve with the result that investors often suffer great losses. Because stock portfolios are thought to be a valid means of avoiding such risks in terms of financial engineering, they have the effect of reducing risk by diversifying investment into several different brands. Based on this, it was attempted to determine an optimal combination of brands that constitute a portfolio and to derive the investment ratio using a multiobjective genetic algorithm, and also to optimize a trading strategy tree using genetic programming. When a performance evaluation was carried out, the system was found to generally obtain the operative results by making it possible to obtain stable profits using a combination of low risk brands. The system was also able to realize low risk investments in all test periods.
Using Simulations to Evaluate Input‐Site and Tetanized‐Site Specificity of Tetanic Effect on Neuronal Networks
Authors: Yada Yuichiro , Haga Tatsuya , Miyazako Hiroki , Takayama Yuzo , Fukayama Osamu , Hoshino Takayuki , Mabuchi Kunihiko
Published: July 2014

Plasticity of neuronal networks is widely investigated as the basis of learning and stimulus‐induced plasticity is one of the remarkable topics. For inducing plasticity and leading a network to a desired state, effective stimuli have to be applied to the network. However, the effect of stimuli on living neuronal networks is difficult to evaluate because of the unsteadiness of the network property. In this paper, we produce a simulated neuronal network and compare the effects of tetanic stimulus at various sites of networks in silico. Using simulation, the tetanic effects can be evaluated irrespective of network transition. We confirmed that the direction of the network plasticity is determined by the tetanized site in the network, and this can be observed only when the proper test‐stimulus site is selected. We conclude that this simulation‐based approach effectively evaluates the stimulus effect on neuronal networks.
The Effect of the Ratio of [M/(B+P)] on the Configuration of Anionic Groups: Synthesis of the Borate–Phosphate LiPb4(BO3)(PO4)2
Authors: Huang Shengshi , Yu Hongwei , Han Jian , Pan Shilie , Jing Qun , Wang Ying , Dong Lingyun , Wu Hongping , Yang Zhihua , Wang Xian
Published: July 2014

Compounds containing both B–O and P–O groups are of wide interest and have been classified into borophosphates and borate–phosphates by R. Kniep et al. In addition to the B/P ratio, analysis results show that regulating the [M/(B+P)] ratio is also an effective strategy to synthesize new borate–phosphates. The first lithium lead borate–phosphate, LiPb4(BO3)(PO4)2, was synthesized by regulating this ratio. This compound crystallizes in the orthorhombic space group Pbca (No. 61). It possesses a 3D structure with a corrugated 2D layer of [B2Pb8O18]∞ that is further connected by a [LiP2O8]∞ chain; both BO3 and PO4 were isolated. First‐principle theoretical studies were performed to aid the understanding of the electronic structures and the linear optical properties. In addition, thermal analysis, IR spectroscopy, and UV/Vis/NIR diffuse reflectance spectroscopy were performed on the reported material.
Amphotericin B microparticles ‘AmbiShell’ from phospholipid and gelatin: Development and investigation by combined DLS and SANS resolves the core‐shell structure
Authors: Johnson Raphael , Nawroth Thomas , Khoshakhlagh Pooneh , Langguth Peter , Schmueser Lars , Hellmann Nadja , Decker Heinz , Szekely Noemi Kinga
Published: July 2014

A novel homogenous core‐shell formulation ‘AmbiShell’ of the hydrophobic antifungal polyene drug Amphotericin B was prepared from the pure drug, lecithin, and gelatin. The established ‘Hydrophilic Solubilisation Technology’ (HST) was used for embedding the lipophilic drug with lecithin and gelatin, yielding core‐shell microparticles of 1 µm size. The particle size of the drug, the formulation, and the thickness of the coating were investigated by using dynamic light scattering (DLS), microscopy, UV–Visible spectroscopy and small angle neutron scattering (SANS). The drug in the formulation was not in the oligomer form but in a competent uptake form, as shown by the UV–Visible spectroscopy. The DLS and microscopy depicted the product to consist of spheres (∼1 µm). The SANS experiment using deuterium contrast matching of the drug cores revealed a thin layer span of 5.6 nm, which is similar, but slightly larger as compared to the biological lipid membranes. The finding offers opportunities for further improvements of the formulation, e.g., by surface modification.

A soluble core‐shell formulation ‘AmbiShell’ of the hydrophobic antifungal polyene drug Amphotericin B was generated from drug, lecithin, and gelatin. The span of the lipid–gelatin shell was estimated by neutron scattering SANS with deuterium contrast matching of the drug core.
Selective, Nanomolar Electrochemical Determination of Environmental Contaminants Dihydroxybenzene Isomers Found in Water Bodies Using Nanocrystalline Zeolite Modified Carbon Paste Electrodes
Authors: Kaur Balwinder , Srivastava Rajendra
Published: July 2014

Nanocrystalline zeolites of different framework structures were prepared by the addition of suitable structure directing agents in the synthesis composition of conventional zeolites. Zeolite modified carbon paste electrodes were constructed for the simultaneous determination of dihydroxybenzene isomers. Nanocrystalline zeolite Beta modified carbon paste electrode exhibited the highest electrocatalytic activity. Under optimum conditions, wide linear range was obtained from 150 nM to 400 µM with lower detection limit of 100, 130, and 100 nM for hydroquinone, catechol, and resorcinol, respectively. The analytical performance of the proposed sensor was demonstrated in the simultaneous determination of dihydroxybenzene isomers in different environmental water samples.
Emerging approaches in predictive toxicology
Authors: Zhang Luoping , McHale Cliona M. , Greene Nigel , Snyder Ronald D. , Rich Ivan N. , Aardema Marilyn J. , Roy Shambhu , Pfuhler Stefan , Venkatactahalam Sundaresan
Published: July 2014

Predictive toxicology plays an important role in the assessment of toxicity of chemicals and the drug development process. While there are several well‐established in vitro and in vivo assays that are suitable for predictive toxicology, recent advances in high‐throughput analytical technologies and model systems are expected to have a major impact on the field of predictive toxicology. This commentary provides an overview of the state of the current science and a brief discussion on future perspectives for the field of predictive toxicology for human toxicity. Computational models for predictive toxicology, needs for further refinement and obstacles to expand computational models to include additional classes of chemical compounds are highlighted. Functional and comparative genomics approaches in predictive toxicology are discussed with an emphasis on successful utilization of recently developed model systems for high‐throughput analysis. The advantages of three‐dimensional model systems and stem cells and their use in predictive toxicology testing are also described. Environ. Mol. Mutagen. 55:679–688, 2014. © 2014 Wiley Periodicals, Inc.