bluuebunny/crossref_metadata_2025 huggingface dataset:
Probability estimation with machine learning methods for dichotomous and multicategory outcome: Theory
Authors: Kruppa Jochen , Liu Yufeng , Biau Gérard , Kohler Michael , König Inke R. , Malley James D. , Ziegler Andreas
Published: January 2014

Probability estimation for binary and multicategory outcome using logistic and multinomial logistic regression has a long‐standing tradition in biostatistics. However, biases may occur if the model is misspecified. In contrast, outcome probabilities for individuals can be estimated consistently with machine learning approaches, includingk‐nearest neighbors (k‐NN), bagged nearest neighbors (b‐NN), random forests (RF), and support vector machines (SVM). Because machine learning methods are rarely used by applied biostatisticians, the primary goal of this paper is to explain the concept of probability estimation with these methods and to summarize recent theoretical findings. Probability estimation ink‐NN, b‐NN, and RF can be embedded into the class of nonparametric regression learning machines; therefore, we start with the construction of nonparametric regression estimates and review results on consistency and rates of convergence. In SVMs, outcome probabilities for individuals are estimated consistently by repeatedly solving classification problems. For SVMs we review classification problem and then dichotomous probability estimation. Next we extend the algorithms for estimating probabilities usingk‐NN, b‐NN, and RF to multicategory outcomes and discuss approaches for the multicategory probability estimation problem using SVM. In simulation studies for dichotomous and multicategory dependent variables we demonstrate the general validity of the machine learning methods and compare it with logistic regression. However, each method fails in at least one simulation scenario. We conclude with a discussion of the failures and give recommendations for selecting and tuning the methods. Applications to real data and example code are provided in a companion article (doi:10.1002/bimj.201300077).
Decoding spatial and temporal features of neuronal cAMP/PKA signaling with FRET biosensors
Authors: Castro Liliana R. V. , Guiot Elvire , Polito Marina , Paupardin‐Tritsch Daniéle , Vincent Pierre
Published: January 2014

Cyclic adenosine monophosphate (cAMP) and the cyclic‐AMP‐dependent protein kinase (PKA) regulate a plethora of cellular functions in virtually all eukaryotic cells. In neurons, the cAMP/PKA signaling cascade controls a number of biological properties such as axonal growth, pathfinding, efficacy of synaptic transmission, regulation of excitability, or long term changes. Genetically encoded optical biosensors for cAMP or PKA are considerably improving our understanding of these processes by providing a real‐time measurement in living neurons. In this review, we describe the recent progress made in the creation of biosensors for cAMP or PKA activity. These biosensors revealed profound differences in the amplitude of the cAMP signal evoked by neuromodulators between various neuronal preparations. These responses can be resolved at the level of individual neurons, also revealing differences related to the neuronal type. At the sub‐cellular level, biosensors reported different signal dynamics in domains like dendrites, cell body, nucleus, and axon. Combining this imaging approach with pharmacology or genetic models points at phosphodiesterases and phosphatases as critical regulatory proteins. Biosensor imaging will certainly emerge as a forefront tool to decipher the subtle mechanics of intracellular signaling. This will certainly help us to understand the mechanism of action of current drugs and foster the development of novel molecules for neuropsychiatric diseases.
Factors impeding enzymatic wheat gluten hydrolysis at high solid concentrations
Authors: Hardt N.A. , Janssen A.E.M. , Boom R.M. , van der Goot A.J.
Published: January 2014

Enzymatic wheat gluten hydrolysis at high solid concentrations is advantageous from an environmental and economic point of view. However, increased wheat gluten concentrations result in a concentration effect with a decreased hydrolysis rate at constant enzyme‐to‐substrate ratios and a decreased maximum attainable degree of hydrolysis (DH%). We here identified the underlying factors causing the concentration effect. Wheat gluten was hydrolyzed at solid concentrations from 4.4% to 70%. The decreased hydrolysis rate was present at all solid concentrations and at any time of the reaction. Mass transfer limitations, enzyme inhibition and water activity were shown to not cause this hydrolysis rate limitation up to 50% solids. However, the hydrolysis rate limitation can be, at least partly, explained by a second‐order enzyme inactivation process. Furthermore, mass transfer impeded the hydrolysis above 60% solids. Addition of enzyme after 24 h at high solid concentrations scarcely increased the DH%, suggesting that the maximum attainable DH% decreases at high solid concentrations. Reduced enzyme activities caused by low water activities can explain this DH% limitation. Finally, a possible influence of the plastein reaction on the DH% limitation is discussed. Biotechnol. Bioeng. 2014;111: 1304–1312. © 2014 Wiley Periodicals, Inc.
In vitro reconstitution of mevalonate pathway and targeted engineering of farnesene overproduction in Escherichia coli
Authors: Zhu Fayin , Zhong Xiaofang , Hu Mengzhu , Lu Lei , Deng Zixin , Liu Tiangang
Published: January 2014

Approaches using metabolic engineering and synthetic biology to overproduce terpenoids, such as the precursors of taxol and artemisinin, in microbial systems have achieved initial success. However, due to the lack of steady‐state kinetic information and incomplete understanding of the terpenoid biosynthetic pathway, it has been difficult to build a highly efficient, universal system. Here, we reconstituted the mevalonate pathway to produce farnesene (a precursor of new jet fuel) in vitro using purified protein components. The information from this in vitro reconstituted system guided us to rationally optimize farnesene production in E. coli by quantitatively overexpressing each component. Targeted proteomic assays and intermediate assays were used to determine the metabolic status of each mutant. Through targeted engineering, farnesene production could be increased predictably step by step, up to 1.1 g/L (∼2,000 fold) 96 h after induction at the shake‐flask scale. The strategy developed to release the potential of the mevalonate pathway for terpenoid overproduction should also work in other multistep synthetic pathways. Biotechnol. Bioeng. 2014;111: 1396–1405. © 2014 Wiley Periodicals, Inc.
Quantitative assessment of in vivo HIV protease activity using genetically engineered QD‐based FRET probes
Authors: Cella Lakshmi N. , Biswas Payal , Yates Marylynn V. , Mulchandani Ashok , Chen Wilfred
Published: January 2014

HIV protease plays a central role in its life cycle leading to release of functional viral particles. It has been successfully used as a therapeutic target to block HIV infection. Several protease inhibitors (PIs) are currently being employed as a part of anti‐HIV therapy. However, the constant genetic drift in the virus leads to accumulation of mutations in both cleavage site and the protease, resulting in resistance and failure of therapy. We reported the use of a quantum dot (QD)‐based protein probe for the in vivo monitoring of HIV‐1 protease activity based on fluorescence resonance energy transfer. In the current study, we demonstrate the utility of this approach by quantifying the in vivo cleavage rates of three known protease and cleavage site mutations in the presence or absence of different PIs. The changes in IC50 values for the different PIs were similar to that observed in patients, validating our assay as a rapid platform for PI screening. Biotechnol. Bioeng. 2014;111: 1082–1087. © 2014 Wiley Periodicals, Inc.
Effects of scaffold architecture on mechanical characteristics and osteoblast response to static and perfusion bioreactor cultures
Authors: Bartnikowski Michal , Klein Travis J. , Melchels Ferry P.W. , Woodruff Maria A.
Published: January 2014

Tissue engineering focuses on the repair and regeneration of tissues through the use of biodegradable scaffold systems that structurally support regions of injury while recruiting and/or stimulating cell populations to rebuild the target tissue. Within bone tissue engineering, the effects of scaffold architecture on cellular response have not been conclusively characterized in a controlled‐density environment. We present a theoretical and practical assessment of the effects of polycaprolactone (PCL) scaffold architectural modifications on mechanical and flow characteristics as well as MC3T3‐E1 preosteoblast cellular response in an in vitro static plate and custom‐designed perfusion bioreactor model. Four scaffold architectures were contrasted, which varied in inter‐layer lay‐down angle and offset between layers, while maintaining a structural porosity of 60 ± 5%. We established that as layer angle was decreased (90° vs. 60°) and offset was introduced (0 vs. 0.5 between layers), structural stiffness, yield stress, strength, pore size, and permeability decreased, while computational fluid dynamics‐modeled wall shear stress was increased. Most significant effects were noted with layer offset. Seeding efficiencies in static culture were also dramatically increased due to offset (∼45% to ∼86%), with static culture exhibiting a much higher seeding efficiency than perfusion culture. Scaffold architecture had minimal effect on cell response in static culture. However, architecture influenced osteogenic differentiation in perfusion culture, likely by modifying the microfluidic environment. Biotechnol. Bioeng. 2014;111: 1440–1451. © 2014 Wiley Periodicals, Inc.
Electrical conditioning of adipose‐derived stem cells in a multi‐chamber culture platform
Authors: Pavesi A. , Soncini M. , Zamperone A. , Pietronave S. , Medico E. , Redaelli A. , Prat M. , Fiore G. B.
Published: January 2014

In tissue engineering, several factors play key roles in providing adequate stimuli for cells differentiation, in particular biochemical and physical stimuli, which try to mimic the physiological microenvironments. Since electrical stimuli are important in the developing heart, we have developed an easy‐to‐use, cost‐effective cell culture platform, able to provide controlled electrical stimulation aimed at investigating the influence of the electric field in the stem cell differentiation process. This bioreactor consists of an electrical stimulator and 12 independent, petri‐like culture chambers and a 3‐D computational model was used to characterize the distribution and the intensity of the electric field generated in the cell culture volume. We explored the effects of monophasic and biphasic square wave pulse stimulation on a mouse adipose‐derived stem cell line (m17.ASC) comparing cell viability, proliferation, protein, and gene expression. Both monophasic (8 V, 2 ms, 1 Hz) and biphasic (+4 V, 1 ms and −4 V, 1 ms; 1 Hz) stimulation were compatible with cell survival and proliferation. Biphasic stimulation induced the expression of Connexin 43, which was found to localize also at the cell membrane, which is its recognized functional mediating intercellular electrical coupling. Electrically stimulated cells showed an induced transcriptional profile more closely related to that of neonatal cadiomyocytes, particularly for biphasic stimulation. The developed platform thus allowed to set‐up precise conditions to drive adult stem cells toward a myocardial phenotype solely by physical stimuli, in the absence of exogenously added expensive bioactive molecules, and can thus represent a valuable tool for translational applications for heart tissue engineering and regeneration. Biotechnol. Bioeng. 2014;111: 1452–1463. © 2014 Wiley Periodicals, Inc.
Chimeric cytochromes P450 engineered by domain swapping and random mutagenesis for producing human metabolites of drugs
Authors: Kang Ji‐Yeon , Ryu Sang Hoon , Park Sun‐Ha , Cha Gun Su , Kim Dong‐Hyun , Kim Keon‐Hee , Hong Austin W. , Ahn Taeho , Pan Jae‐Gu , Joung Young Hee , Kang Hyung‐Sik , Yun Chul‐Ho
Published: January 2014

Human drug metabolites produced by cytochrome P450 enzymes are critical for safety testing and may themselves act as drugs or leads in the drug discovery and development process. Here, highly active chimeric fusion proteins (chimeras) were obtained by reductase domain swapping of mutants at key catalytic residues of the heme domain with that of a natural variant (CYP102A1.2) of P450 BM3 (CYP102A1.1) from Bacillus megaterium. Random mutagenesis at the heme domain of the chimera was also used to generate chimeric mutants that were more active and diverse than the chimeras themselves. To determine whether the chimeras and several mutants of the highly active chimera displayed enhanced catalytic activity and, more importantly, whether they acquired activities of biotechnological importance, we measured the oxidation activities of the chimeras and chimeric mutants toward human P450 substrates, mainly drugs. Some of the chimeric mutants showed high activity toward typical human P450 substrates including drugs. Statin leads, especially chiral products, with inhibitory effects toward HMG‐CoA reductase could be obtained from metabolites of statin drugs generated using these chimeric mutants. This study reveals the critical role of the reductase domain for the activity of P450 BM3 and shows that chimeras generated by domain swapping can be used to develop industrial enzymes for the synthesis of human metabolites from drugs and drug leads. Biotechnol. Bioeng. 2014;111: 1313–1322. © 2014 Wiley Periodicals, Inc.
The impact of elevated CO2 concentration on the quality of algal starch as a potential biofuel feedstock
Authors: Tanadul Orn‐u‐ma , VanderGheynst Jean S. , Beckles Diane M. , Powell Ann L.T. , Labavitch John M.
Published: January 2014

Cultured microalgae are viewed as important producers of lipids and polysaccharides, both of which are precursor molecules for the production of biofuels. This study addressed the impact of elevated carbon dioxide (CO2) on Chlorella sorokiniana production of starch and on several properties of the starch produced. The production of C. sorokiniana biomass, lipid and starch were enhanced when cultures were supplied with 2% CO2. Starch granules from algae grown in ambient air and 2% CO2 were analyzed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The granules from algae grown in 2% CO2 were disk‐shaped and contained mainly stromal starch; granules from cultures grown in ambient air were cup‐shaped with primarily pyrenoid starch. The granules from cells grown in 2% CO2 had a higher proportion of the accumulated starch as the highly branched, amylopectin glucan than did granules from cells grown in air. The rate of hydrolysis of starch from 2% CO2‐grown cells was 1.25 times greater than that from air‐grown cells and 2–11 times higher than the rates of hydrolysis of starches from cereal grains. These data indicate that culturing C. sorokiniana in elevated CO2 not only increases biomass yield but also improves the structure and composition of starch granules for use in biofuel generation. These modifications in culture conditions increase the hydrolysis efficiency of the starch hydrolysis, thus providing potentially important gains for biofuel production. Biotechnol. Bioeng. 2014;111: 1323–1331. © 2014 Wiley Periodicals, Inc.
Prognostic subdivision of ypT3 rectal tumours according to extension beyond the muscularis propria
Authors: Merkel S , Weber K , Schellerer V , Göhl J , Fietkau R , Agaimy A , Hohenberger W , Hermanek P
Published: January 2014

Background

The subdivision of T3 in rectal carcinoma according to the depth of invasion into perirectal fat has been recommended in the TNM Supplement since 1993. This study assessed the prognostic impact of this pathological staging in tumours removed after neoadjuvant chemoradiotherapy (ypT3).

Methods

Data from patients with ypT3 rectal carcinoma (less than 12 cm from the anal verge) treated with neoadjuvant chemoradiation and total mesorectal excision were analysed. Tumour category ypT3 was subdivided into ypT3a (5 mm or less) and ypT3b (more than 5 mm), based on histological measurements of maximal tumour invasion beyond the outer border of the muscularis propria.

Results

Important differences between ypT3a (81 patients) and ypT3b (43) were found in 5-year rates of locoregional recurrence (7 versus 18 per cent; P = 0·049), distant metastasis (20 versus 41 per cent; P = 0·002), disease-free survival (73 versus 47 per cent; P = 0·001), overall survival (79 versus 74 per cent; P = 0·036) and cancer-related survival (81 versus 74 per cent; P = 0·007). In Cox regression analyses, the ypT3 subclassification was identified as an independent prognostic factor for disease-free (ypT3b: hazard ratio (HR) 2·13, 95 per cent confidence interval 1·16 to 3·89; P = 0·014), observed (ypT3b: HR 2·02, 1·05 to 3·87; P = 0·035) and cancer-related (ypT3b: HR 2·46, 1·20 to 5·04; P = 0·014) survival. Extramural venous invasion was found to be an additional prognostic factor, but the pathological node category after chemoradiotherapy (ypN) did not influence survival.

Conclusion

In ypT3 rectal carcinomas, the proposed subclassification is superior to ypN in predicting prognosis.
Can JWH‐210 and JWH‐122 be detected in adipose tissue four weeks after single oral drug administration to rats?
Authors: Schaefer Nadine , Peters Benjamin , Bregel Dietmar , Maurer Hans H. , Schmidt Peter H. , Ewald Andreas H.
Published: January 2014

Synthetic cannabinoids such as alkylindole derivatives entered the illicit drug market worldwide a few years ago. Only a few data are available concerning their pharmacokinetics, in particular their distribution and persistence in adipose tissue. For the present study, rats were administered a single 20 mg/kg oral dose of JWH‐210 or JWH‐122. After one month, they were dissected and adipose tissue was taken in order to study whether JWH‐210 and JWH‐122 persisted in this body sample. After extraction, the samples were analyzed by liquid chromatographic–mass spectrometry (LC‐QTrap‐MS). Validation of the analytical method for adipose tissue is also presented. The results of the matrix effects determination ranged between 30.6 and 43.8%. The limits of detection for JWH‐210 and JWH‐122 were 0.8 and 1.0 ng/g and lower limits of quantification were 3.7 and 2.1 ng/g, respectively. Calibration curves ranged from 10 to 75 ng/g for JWH‐210 and from 5 to 50 ng/g for JWH‐122. Intra‐ and interday precision values were lower than 15% and bias values within ±15%. Applying this method, in adipose tissue specimens obtained 4 weeks after single drug administration, JWH‐210 and JWH‐122 were detected in concentrations of 116 and 9 ng/g, respectively. Copyright © 2014 John Wiley & Sons, Ltd.
Simultaneous Inhibition Assay for Human and Microbial Kinases via MALDI‐MS/MS
Authors: Smith Anne Marie E. , Brennan John D.
Published: January 2014

Selective inhibition of one kinase over another is a critical issue in drug development. For antimicrobial development, it is particularly important to selectively inhibit bacterial kinases, which can phosphorylate antimicrobial compounds such as aminoglycosides, without affecting human kinases. Previous work from our group showed the development of a MALDI‐MS/MS assay for the detection of small molecule modulators of the bacterial aminoglycoside kinase APH3′IIIa. Herein, we demonstrate the development of an enhanced kinase MALDI‐MS/MS assay involving simultaneous assaying of two kinase reactions, one for APH3′IIIa, and the other for human protein kinase A (PKA), which leads to an output that provides direct information on selectivity and mechanism of action. Specificity of the respective enzyme substrates were verified, and the assay was validated through generation of Z′‐factors of 0.55 for APH3′IIIa with kanamycin and 0.60 for PKA with kemptide. The assay was used to simultaneously screen a kinase‐directed library of mixtures of ten compounds each against both enzymes, leading to the identification of selective inhibitors for each enzyme as well as one non‐selective inhibitor following mixture deconvolution.
Heat shock‐induced dissociation of TRF2 from telomeres does not initiate a telomere‐dependent DNA damage response
Authors: Petrova Nadezhda V. , Velichko Artem K. , Kantidze Omar L. , Razin Sergey V.
Published: January 2014

Telomeric repeat binding factor 2 (TRF2) is a well‐studied shelterin complex subunit that plays a major role in the protection of chomosome ends and the prevention of the telomere‐associated DNA damage response. We show that heat shock induces the dissociation of TRF2 from telomeres in human primary and cancer cell cultures. TRF2 is not simply degraded in response to heat shock, but redistributed thoughout the nucleoplasm. This TRF2 depletion/redistribution does not initiate the DNA damage response at chomosome termini.
Metal‐Ion‐Regulated Miniature DNA‐Binding Proteins Based on GCN4 and Non‐native Regulation Sites
Authors: Oheix Emmanuel , Peacock Anna F. A.
Published: January 2014

The design of artificial peptide dimers containing polypyridine switching domains, for which metal‐ion coordination is shown to regulate DNA binding, is reported. Short peptides, based on the basic domain of the GCN4 transcription factor (GCN4bd), dimerised with either 2,2′‐bipyridine (bipy(GCN4bd)2) or 2,2′:6′,2′′‐terpyridine (terpy(GCN4bd)2) linker units, undergo a conformational rearrangement on CuII and ZnII coordination. Depending on the linker substitution pattern, this is proposed to alter the relative alignment of the two peptide moieties, and in turn regulate DNA binding. Circular dichroism and UV–visible spectroscopy reveal that CuII and ZnII coordination promotes binding to DNA containing the CRE target site, but to a differing and opposite degree for the two linkers, and that the metal‐ion affinity for terpy(GCN4bd)2 is enhanced in the presence of CRE DNA. Binding to DNA containing the shorter AP1 target site, which lacks a single nucleobase pair compared to CRE, as well as half‐CRE, which contains only half of the CRE target site, was also investigated. CuII and ZnII coordination to terpy(GCN4bd)2 promotes binding to AP1 DNA, and to a lesser extent half‐CRE DNA. Whereas, bipy(GCN4bd)2, for which interpeptide distances are largely independent of metal‐ion coordination and less suitable for binding to these shorter sites, displays allosteric ineffective behaviour in these cases. These findings for the first time demonstrate that biomolecular recognition, and specifically sequence‐selective DNA binding, can be controlled by metal‐ion coordination to designed switching units, non‐native regulation sites, in artificial biomolecules. We believe that in the future these could find a wide range of applications in biotechnology.
Tandem Pd/Au‐Catalyzed Route to α‐Sulfenylated Carbonyl Compounds from Terminal Propargylic Alcohols and Thiols
Authors: Biswas Srijit , Watile Rahul A. , Samec Joseph S. M.
Published: January 2014

An efficient and highly atom‐economical tandem Pd/Au‐catalyzed route to α‐sulfenylated carbonyl compounds from terminal propargylic alcohols and thiols has been developed. This one‐step procedure has a wide substrate scope with respect to substituents at the α‐position of the alcohol. Both aromatic and aliphatic thiols generated the α‐sulfenylated carbonyl products in good to excellent yields. A mechanism is proposed in which the reaction proceeds through a Pd‐catalyzed regioselective hydrothiolation at the terminal triple bond of the propargyl alcohol followed by an Au‐catalyzed 1,2‐hydride migration.
Silver‐Catalyzed Cross‐Coupling of Propargylic Alcohols with Isocyanides: An Atom‐Economical Synthesis of 2,3‐Allenamides
Authors: Liu Jianquan , Liu Zhenhua , Wu Nannan , Liao Peiqiu , Bi Xihe
Published: January 2014

Cross‐coupling reactions between propargylic alcohols and isocyanides, by means of silver catalysis, have been described. This new reaction is both atom and step efficient and is applicable to a broad scope of substrates, allowing the synthesis of a range of synthetically valuable 2,3‐allenamides in moderate to excellent yields.
Favoring Trienamine Activation through Unconjugated Dienals: Organocatalytic Enantioselective Remote Functionalization of Alkenes
Authors: Prieto Liher , Talavera Garazi , Uria Uxue , Reyes Efraim , Vicario Jose L. , Carrillo Luisa
Published: January 2014

Unconjugated 2,5‐dienals are more reactive substrates than the corresponding fully conjugated α,β,γ,δ‐unsaturated aldehydes towards organocatalytic activation through trienamine intermediates. This difference in reactivity has been demonstrated in the Diels–Alder reaction with nitroalkenes, a reaction that proceeds with clean β,ε‐selectivity to afford the final products in high yields and stereoselectivities, the related polyconjugated 2,4‐dienals being completely unreactive.
Stable Nanosuspensions via the Deposition of Gas‐Borne Nanoparticles of Active Pharmaceutical Ingredients in Bubble Columns
Authors: Koch Dagmar , Weber Alfred P.
Published: January 2014

Der Transport von Partikeln aus der Gasphase in eine Flüssigkeit in Blasensäulen kann zur Herstellung stabiler Nanosuspensionen aus pharmazeutischen Wirkstoffen eingesetzt werden. In der vorliegenden Arbeit wird das Verhalten gasgetragener Nanopartikel (Kohlenstoff und Phytosterol) beim Übergang aus aufsteigenden Gasblasen in die Suspensionsflüssigkeit für Wasser und zwei Stabilisatorlösungen (Polyvinylpyrrolidon K25 und Tween®80) untersucht. Neben einem Modell zur Beschreibung der Abscheideeffizienz wird auch die Langzeitstabilität der Phytosterol‐Suspensionen diskutiert.
Heat transfer investigation of laminar developing flow of nanofluids in a microchannel based on Eulerian–Lagrangian approach
Authors: Mirzaei Mostafa , Saffar‐Avval Majid , Naderan Hamid
Published: January 2014

In this article, laminar forced convection of nanofluids in a parallel plate microchannel under constant wall temperature is numerically investigated. A Eulerian–Lagrangian two‐phase method is employed to simulate the flow and heat transfer of nanofluid in the microchannel. Navier–Stokes equations were solved using a finite difference method based on the projection algorithm while a Runge–Kutta method have been used to solve Lagrangian equations of the particle phase. A parallel code is developed on a cluster of processors which indicates a good performance to solve an Eulerian–Lagrangian problem. The convective heat transfer coefficient of nanofluids is better than the base fluid particularly in the entrance region. The results based on two phase modelling, show a slightly greater improvement in the heat transfer coefficient in comparison to the homogeneous single‐phase nanofluid method. The obtained results show that the heat transfer enhancement increases as the nanoparticles volume fraction increases, and decreases with the Reynolds number for Cu–water nanofluid, while the alumina–water nanofluid have a different behaviour. A comparison of two different nanofluids showed the importance considering all of the nanofluid's properties not just thermal conductivity.
Uranyl Ions Removal by Quercus macrenthera Gall's Extract‐Based Cryogels with Extreme Characteristics
Authors: Bağda Esra , Zonuz Nuray Akkaya
Published: January 2014

In this study, one type of oak galls (galls of Quercus macrenthera, QMG) was used as tannin source for the production of tannic acid‐based cryogels (CRGs). QMG‐CRGs were characterized with scanning electron microscopy and attenuated total reflectance infrared. The produced CRGs have excellent characteristics such as extreme lightweightness. They look like sponges and are so elastic that they can easily absorb water and the water content can be removed easily by only compressing. These CRGs are able to swell violently immersed in aqueous solution. The prepared CRGs were used in removing uranyl ions from aqueous solutions. Some experimental parameters which affect the adsorption process as pH of the solution, initial uranyl concentration, and sorbent dosage have been investigated. The experimental data were analyzed by the Langmuir and Freundlich isotherm models and kinetic data were treated with pseudo first and second‐order models. It is found that the adsorption data of uranium is equally well described by both Langmuir and Freundlich models, besides kinetic data strictly fits the pseudo‐second‐order rate model.
Experimental Investigation and Kinetic Modeling of p‐Nitrophenol and Phenol by Kissiris‐Immobilized Ralstonia eutropha in a Batch Reactor
Authors: Motamedi Mahdi , Habibi Alireza , Maleki Mohammad , Vahabzadeh Farzaneh
Published: January 2014

Co‐metabolic degradation of p‐nitrophenol (PNP) and phenol by kissiris‐immobilized Ralstonia eutropha cells was studied in a batch bioreactor operated in recycling mode (30°C, initial pH of 7.7, aeration rate of 0.5 vvm, and recycling flow rate of 25 mL min−1). Decreasing trends of specific degradation rates of phenol (qSg) and PNP (qSng) with an increase of initial PNP concentration, were mathematically modeled considering the competitive inhibition between growth and non‐growth substrates and self‐inhibition of non‐growth substrate. A non‐linear regression on the equations used in defining of qSg, and qSng, was used to estimate the relevant kinetic parameters. On the best fitted curve, the kinetic parameters were qmax Sg = 0.032 g Phenol g Cell−1 h−1, Km Sg = 442.9 mg L−1, qmax Sng = 0.0056 g Phenol g Cell−1 h−1, Km Sng = 181.2 mg L−1, and KSng = 0.489 mg L−1. These parameters were used for dynamic prediction of the substrates concentration feature during co‐metabolic degradation experiments.
Sharpening the focus on causes and timing of readmission after radical cystectomy for bladder cancer
Authors: Hu Michael , Jacobs Bruce L. , Montgomery Jeffrey S. , He Chang , Ye Jun , Zhang Yun , Brathwaite Julien , Morgan Todd M. , Hafez Khaled S. , Weizer Alon Z. , Gilbert Scott M. , Lee Cheryl T. , Lavieri Mariel S. , Helm Jonathan E. , Hollenbeck Brent K. , Skolarus Ted A.
Published: January 2014

BACKGROUND

Readmissions after radical cystectomy are common, burdensome, and poorly understood. For these reasons, the authors conducted a population‐based study that focused on the causes of and time to readmission after radical cystectomy.

METHODS

Using Surveillance, Epidemiology, and End Results‐Medicare data, at total of 1782 patients who underwent radical cystectomy from 2003 through 2009 were identified. A piecewise exponential model was used to examine reasons for readmission as well as patient and clinical factors associated with the timing of readmission.

RESULTS

One in 4 patients (25.5%) were readmitted within 30 days of discharge after radical cystectomy. Compared with patients without readmission, those readmitted were similar with regard to age, sex, and race. Readmitted patients had more complications (33.8% vs 13.9%; P < .001) and were more likely to have been discharged to skilled nursing facilities from their index admission (P < .001). The average time to readmission and subsequent length of stay were 11.5 days and 6.7 days, respectively. The majority of readmissions (67.4%) occurred within 2 weeks of discharge, 66.8% had emergency department charges, and 25.9% involved intensive care unit use. Although the spectrum of reasons for readmission varied over the 4 weeks after discharge, the most common included infection (51.4%), failure to thrive (36.3%), and urinary (33.2%) and gastrointestinal (23.1%) etiologies; 95.8% of patients had ≥ 1 of these diagnosis groups present at the time of readmission.

CONCLUSIONS

Readmissions after radical cystectomy are common and time‐dependent. Interventions to prevent and reduce the readmission burden after cystectomy likely need to focus on the first 2 weeks after discharge, take into consideration the spectrum of reasons for readmission, and target high‐risk individuals. Cancer 2014;120:1409–1416. © 2014 American Cancer Society.
Immigration factors and prostate cancer survival among Hispanic men in California: Does neighborhood matter?
Authors: Schupp Clayton W. , Press David J. , Gomez Scarlett Lin
Published: January 2014

BACKGROUND

Hispanics are more likely than other racial/ethnic groups in the United States to be diagnosed with later stage of prostate cancer, yet they have lower prostate cancer mortality rates. The authors evaluated the impact of nativity and neighborhood‐level Hispanic ethnic enclave on prostate cancer survival among Hispanics.

METHODS

A total of 35,427 Hispanic men diagnosed with invasive prostate cancer from 1995 through 2008 in the California Cancer Registry were studied; vital status data were available through 2010. Block group‐level neighborhood measures were developed from US Census data. Stage‐stratified Cox proportional hazards models were used to assess the effect of nativity and ethnic enclave on prostate cancer survival.

RESULTS

In models adjusted for neighborhood socioeconomic status and other individual factors, foreign‐born Hispanics were found to have a significantly lower risk of prostate cancer survival (hazards ratio [HR], 0.81; 95% confidence interval [95% CI], 0.75‐0.87). Living in an ethnic enclave appeared to modify this effect, with the survival advantage slightly more pronounced in the high ethnic enclave neighborhoods (HR, 0.78; 95% CI, 0.71‐0.86) compared with low ethnic enclave neighborhoods (HR, 0.86; 95% CI, 0.76‐0.98).

CONCLUSIONS

Despite lower socioeconomic status, Hispanic immigrants have better survival after prostate cancer than US‐born Hispanics and this pattern was more striking among those living in ethnic enclaves. Identifying the modifiable individual and neighborhood‐level factors that facilitate this survival advantage in Hispanic immigrants may help to inform specific interventions to improve survival among all patients. Cancer 2014;120:1401–1408. © 2014 American Cancer Society.
Growing indication for FNA to study and analyze tumor heterogeneity at metastatic sites
Authors: Beca Francisco , Schmitt Fernando
Published: January 2014

In routine practice, suspected metastases in patients with cancer are only occasionally biopsied, primarily because of the cost and invasiveness of the procedure. However, biopsies of metastatic lesions can be valuable, not only in confirming the presence of metastatic disease, but also in revealing unsuspected benign disease or secondary malignancies. In addition, such biopsies also allow the assessment of biomarkers that might differ from those on primary tumor cells, and can thereby facilitate selection of the optimal treatment. Because of the increasing recognition of clonal and phenotypic heterogeneity of tumors, we anticipate that in the near future, biopsying of metastatic lesions will constitute a standard‐of‐care practice, allowing assessment of molecular differences between the primary tumor and metastatic lesions. In our opinion, fine‐needle aspiration is currently the best method for making repeated biopsies to monitor the tumor: it is minimally invasive, safe, and cost effective and can be coupled with modern ancillary techniques. Here we provide an up‐to‐date review of the clinical implications of tumor heterogeneity in metastatic disease and the ancillary molecular techniques used in cytology; we also discuss the role of modern cytology in contemporary diagnosis and management of metastatic cancer. Cancer (Cancer Cytopathol) 2014;122:504–511. © 2014 American Cancer Society.
The role of voltage‐gated calcium channels in neurotransmitter phenotype specification: Coexpression and functional analysis in Xenopus laevis
Authors: Lewis Brittany B. , Miller Lauren E. , Herbst Wendy A. , Saha Margaret S.
Published: January 2014

Calcium activity has been implicated in many neurodevelopmental events, including the specification of neurotransmitter phenotypes. Higher levels of calcium activity lead to an increased number of inhibitory neural phenotypes, whereas lower levels of calcium activity lead to excitatory neural phenotypes. Voltage‐gated calcium channels (VGCCs) allow for rapid calcium entry and are expressed during early neural stages, making them likely regulators of activity‐dependent neurotransmitter phenotype specification. To test this hypothesis, multiplex fluorescent in situ hybridization was used to characterize the coexpression of eight VGCC α1 subunits with the excitatory and inhibitory neural markers xVGlut1 and xVIAAT in Xenopus laevis embryos. VGCC coexpression was higher with xVGlut1 than xVIAAT, especially in the hindbrain, spinal cord, and cranial nerves. Calcium activity was also analyzed on a single‐cell level, and spike frequency was correlated with the expression of VGCC α1 subunits in cell culture. Cells expressing Cav2.1 and Cav2.2 displayed increased calcium spiking compared with cells not expressing this marker. The VGCC antagonist diltiazem and agonist (−)BayK 8644 were used to manipulate calcium activity. Diltiazem exposure increased the number of glutamatergic cells and decreased the number of γ‐aminobutyric acid (GABA)ergic cells, whereas (−)BayK 8644 exposure decreased the number of glutamatergic cells without having an effect on the number of GABAergic cells. Given that the expression and functional manipulation of VGCCs are correlated with neurotransmitter phenotype in some, but not all, experiments, VGCCs likely act in combination with a variety of other signaling factors to determine neuronal phenotype specification. J. Comp. Neurol. 522:2518–2531, 2014. © 2014 Wiley Periodicals, Inc.
Distribution of neurotransmitter receptors and zinc in the pigeon (Columba livia) hippocampal formation: A basis for further comparison with the mammalian hippocampus
Authors: Herold Christina , Bingman Verner P. , Ströckens Felix , Letzner Sara , Sauvage Magdalena , Palomero‐Gallagher Nicola , Zilles Karl , Güntürkün Onur
Published: January 2014

The avian hippocampal formation (HF) and mammalian hippocampus share a similar functional role in spatial cognition, but the underlying neuronal mechanisms allowing the functional similarity are incompletely understood. To understand better the organization of the avian HF and its transmitter receptors, we analyzed binding site densities for glutamatergic AMPA, NMDA, and kainate receptors; GABAA receptors; muscarinic M1, M2 and nicotinic (nACh) acetylcholine receptors; noradrenergic α1 and α2 receptors; serotonergic 5‐HT1A receptors; dopaminergic D1/5 receptors by using quantitative in vitro receptor autoradiography. Additionally, we performed a modified Timm staining procedure to label zinc. The regionally different receptor densities mapped well onto seven HF subdivisions previously described. Several differences in receptor expression highlighted distinct HF subdivisions. Notable examples include 1) high GABAA and α1 receptor expression, which rendered distinctive ventral subdivisions; 2) high α2 receptor expression, which rendered distinctive a dorsomedial subdivision; 3) distinct kainate, α2, and muscarinic receptor densities that rendered distinctive the two dorsolateral subdivisions; and 4) a dorsomedial region characterized by high kainate receptor density. We further observed similarities in receptor binding densities between subdivisions of the avian and mammalian HF. Despite the similarities, we propose that 300 hundred million years of independent evolution has led to a mosaic of similarities and differences in the organization of the avian HF and mammalian hippocampus and that thinking about the avian HF in terms of the strict organization of the mammalian hippocampus is likely insufficient to understand the HF of birds. J. Comp. Neurol. 522:2553–2575, 2014. © 2014 Wiley Periodicals, Inc.
A unique ion channel clustering domain on the axon initial segment of mammalian neurons
Authors: King Anna N. , Manning Colleen F. , Trimmer James S.
Published: January 2014

The axon initial segment (AIS) plays a key role in initiation of action potentials and neuronal output. The plasma membrane of the AIS contains high densities of voltage‐gated ion channels required for these electrical events, and much recent work has focused on defining the mechanisms for generating and maintaining this unique neuronal plasma membrane domain. The Kv2.1 voltage‐gated potassium channel is abundantly present in large clusters on the soma and proximal dendrites of mammalian brain neurons. Kv2.1 is also a component of the ion channel repertoire at the AIS. Here we show that Kv2.1 clusters on the AIS of brain neurons across diverse mammalian species including humans define a noncanonical ion channel clustering domain deficient in Ankyrin‐G. The sites of Kv2.1 clustering on the AIS are sites where cisternal organelles, specialized intracellular calcium release membranes, come into close apposition with the plasma membrane, and are also sites of clustering of γ‐aminobutyric acid (GABA)ergic synapses. Using an antibody specific for a single Kv2.1 phosphorylation site, we find that the phosphorylation state differs between Kv2.1 clusters on the proximal and distal portions of the AIS. Together, these studies show that the sites of Kv2.1 clustering on the AIS represent specialized domains containing components of diverse neuronal signaling pathways that may contribute to local regulation of Kv2.1 function and AIS membrane excitability. J. Comp. Neurol. 522:2594–2608, 2014. © 2014 Wiley Periodicals, Inc.
Single‐Molecule Metal‐Induced Energy Transfer (smMIET): Resolving Nanometer Distances at the Single‐Molecule Level
Authors: Karedla Narain , Chizhik Alexey I. , Gregor Ingo , Chizhik Anna M. , Schulz Olaf , Enderlein Jörg
Published: January 2014

We present a new concept for measuring distance values of single molecules from a surface with nanometer accuracy using the energy transfer from the excited molecule to surface plasmons of a metal film. We measure the fluorescence lifetime of individual dye molecules deposited on a dielectric spacer as a function of a spacer thickness. By using our theoretical model, we convert the lifetime values into the axial distance of individual molecules. Similar to Förster resonance energy transfer (FRET), this allows emitters to be localized with nanometer accuracy, but in contrast to FRET the distance range at which efficient energy transfer takes place is an order of magnitude larger. Our technique can be potentially used as a tool for measuring intramolecular distances of biomolecules and complexes.
The Origin of the “Snap‐In” in the Force Curve between AFM Probe and the Water/Gas Interface of Nanobubbles
Authors: Song Yang , Zhao Binyu , Zhang Lijuan , Lü Junhong , Wang Shuo , Dong Yaming , Hu Jun
Published: January 2014

The long‐range attractive force or “snap‐in” is an important phenomenon usually occurring when a solid particle interacts with a water/gas interface. By using PeakForce quantitative nanomechanics the origin of snap‐in in the force curve between the atomic force microscopy (AFM) probe and the water/gas interface of nanobubbles has been investigated. The snap‐in frequently happened when the probe was preserved for a certain time or after being used for imaging solid surfaces under atmospheric conditions. In contrast, imaging in liquids rarely induced a snap‐in. After a series of control experiments, it was found that the snap‐in can be attributed to hydrophobic interactions between the water/gas interface and the AFM probe, which was either modified or contaminated with hydrophobic material. The hydrophobic contamination could be efficiently removed by a conventional plasma‐cleaning treatment, which prevents the occurring of the snap‐in. In addition, the adsorption of sodium dodecyl sulfate onto the nanobubble surface changed the water/gas interface into hydrophilic, which also eliminated the snap‐in phenomenon.
Ferrocene‐Modified Carbon Nitride for Direct Oxidation of Benzene to Phenol with Visible Light
Authors: Ye Xiangju , Cui Yanjuan , Wang Xinchen
Published: January 2014

Ferrocene moieties were heterogenized onto carbon nitride polymers by a covalent CN linkage bridging the two conjugation systems, enabling the merging of the redox function of ferrocene with carbon nitride photocatalysis to construct a heterogeneous Photo‐Fenton system for green organocatalysis at neutral conditions. The synergistic donor–acceptor interaction between the carbon nitride matrix and ferrocene group, improved exciton splitting, and coupled photocatalytic performance allowed the direct synthesis of phenol from benzene in the presence of H2O2 under visible light irradiation. This innovative modification method will offer an avenue to construct functionalized two‐dimensional polymers useful also for other green synthesis processes using solar irradiation.
Low complexity timing estimation and resynchronization for asynchronous bidirectional communications with multiple antenna relay
Authors: Fang Zhaoxi , Liang Feng , Wang Zunyi , Chen Danjiang
Published: January 2014

In this paper, we consider an asynchronous bidirectional communication system over flat fading channels in which the two source nodes are not perfectly synchronized. A low complexity pilot aided timing estimation and resynchronization scheme is proposed to combat the fractional asynchronous delay between the two source nodes. In the proposed scheme, cyclic prefixed single carrier block transmission is implemented at the two sources and frequency domain orthogonal pilots are transmitted to the relay simultaneously. After timing and channel estimation at the relay, a fractionally spaced frequency domain equalizer is employed at the relay to resynchronize the received mixed signals. With the proposed resynchronization scheme, the data detection at the two sources is the same as in a perfect synchronized system, because the two asynchronous signals are already resynchronized at the relay node. Simulation results show that the performance gap between the proposed scheme and the perfect synchronized system is within 1 dB when there are four antennas at the relay. Copyright © 2014 John Wiley & Sons, Ltd.
The syntheses, characterization and in vitro metabolism of nitracaine, methoxypiperamide and mephtetramine
Authors: Power John D. , Scott Kenneth R. , Gardner Elizabeth A. , Curran McAteer Bronagh M. , O'Brien John E. , Brehon Margaret , Talbot Brian , Kavanagh Pierce V.
Published: January 2014

Three legal highs; nitracaine (3‐(diethylamino)‐2,2‐dimethylpropyl 4‐nitrobenzoate), methoxypiperamide (MEOP, (4‐methoxyphenyl)(4‐methylpiperazin‐1‐yl)methanone) and mephtetramine (MTTA, 2‐((methylamino)methyl)‐3,4‐dihydronaphthalen‐1(2H)‐one) appeared in 2013 as new psychoactive substances (NPS) on Internet websites selling ‘research chemicals’. These compounds were synthesized and analyzed via our synthesize, analyze, and metabolize (SAM) protocol. Nitracaine was synthesized by the transesterification of methyl 4‐nitrobenzoate with 3‐(diethylamino)‐2,2‐dimethylpropan‐1‐ol. Methoxypiperamide was synthesized by the reaction of 4‐methoxybenzoyl chloride with 1‐methylpiperazine, and mephtetramine through the Mannich reaction of 1‐tetralone with paraformaldehyde and methylamine hydrochloride. Each compound was characterized by nuclear magnetic resonance (NMR), gas chromatography with electron impact mass spectrometry (GC‐EIMS), liquid chromatography‐electrospray ionization‐mass spectrometry (LC‐ESI‐MS), and high resolution electrospray ionization mass spectrometry (HR‐ESI‐MS). A sample of nitracaine was also test‐purchased from an Internet vendor and its structure confirmed by GC‐EIMS and LC‐ESI‐MS. Finally, the in vitro metabolism of the nitracaine, mephtetramine, and methoxypiperamide was investigated, using a human microsomal liver extract, in order to tentatively identify potential metabolites that may be encountered in the analysis of biological samples in clinical or toxicology labs. The use of our SAM protocol highlights the ability of academic research labs to quickly respond to and disseminate information about emerging NPS. Copyright © 2014 John Wiley & Sons, Ltd.