bluuebunny/crossref_metadata_2025 huggingface dataset:
Dense understory and absence of capuchin monkeys (Sapajus xanthosternos) predict higher density of common marmosets (Callithrix jacchus) in the Brazilian Northeast
Authors: Hilário Renato R. , Ferrari Stephen F.
Published: November 2014

Understanding the effects of habitat structure and other environmental variables on the density of a species can help define its habitat preferences and key ecological determinants of population parameters. The present study evaluated the effects of fragment size, the presence of a key predator/competitor, the yellow‐breasted capuchin (Sapajus xanthosternos), primary productivity, the abundance of bromeliads, and habitat structure on the population density of the common marmoset (Callithrix jacchus). A total of 21 fragments were surveyed within a 350‐km long zone of coastal Atlantic Forest representing the southern extreme of the distribution of the species in the Brazilian Northeast. An index of marmoset density was generated for each site based on playback surveys. The relationship between the density of marmosets and a set of parameters was evaluated by multiple regression. A Principal Components Analysis (PCA) condensed the five variables of habitat structure into two principal components, which contained 85% of their combined variation. The model that best explained the density of marmosets (R2 = 59.1) contained the second PCA component and the presence/absence of capuchins. The analysis indicated that the marmosets prefer forests with denser understory, whether or not they are secondary habitats. The negative effect of the presence of capuchins may be related to predation pressure. The results of this study indicate that multiple‐site studies may provide important insights into the habitat preferences of primate species and the factors that affect their population density. Am. J. Primatol. 77:425–433, 2015. © 2014 Wiley Periodicals, Inc.
Optimization of electrical stimulation parameters for electro‐responsive hydrogels for biomedical applications
Authors: Jackson Nathan , Stam Frank
Published: November 2014

Electro‐responsive hydrogels (ERH) are highly researched materials for biomedical applications. However, most of the research is concentrated on the synthesis of novel hydrogels for various applications, and little effort has been made to investigate electrode configuration and optimization of electrical stimulation parameters. This article used a three‐dimensional interdigitated (IDT) electrode configuration device to investigate the optimization of electrical actuation parameters in order to radially deswell an ERH. A Pluronic‐bismethacrylate hydrogel modified with hydrolyzed methacrylic acid was used as the ERH material. This article reports on using novel electro‐actuation parameters and electrode configurations to maximize radial deswelling of an ERH for biomedical applications. The optimal waveform was assessed for, varying electrode spacing's, voltages, duty cycles, and frequencies. The results show that a maximum deswelling occurred with a DC pulsed monophasic waveform, with IDT electrodes spaced close enough to create a relatively uniform electric field, with a peak voltage of 5 V at 1 kHz, and 50% duty cycle. This resulted in a deswelling of 320% in Krebs solution. Electrochemical impedance spectroscopy results show that the impedance is dependent on the ionic concentration of the fluid environment and that the impedance decreases with increasing frequency. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41687.
A Comparative Study of Trabecular Bone Mass Distribution in Cursorial and Non‐Cursorial Limb Joints
Authors: Chirchir Habiba
Published: November 2014

Skeletal design among cursorial animals is a compromise between a stable body that can withstand locomotor stress and a light design that is energetically inexpensive to grow, maintain, and move. Cursors have been hypothesized to reduce distal musculoskeletal mass to maintain a balance between safety and energetic cost due to an exponential increase in energetic demand observed during the oscillation of the distal limb. Additionally, experimental research shows that the cortical bone in distal limbs experiences higher strains and remodeling rates, apparently maintaining lower mass at the expense of a smaller safety factor. This study tests the hypothesis that the trabecular bone mass in the distal limb epiphyses of cursors is relatively lower than that in the proximal limb epiphyses to minimize the energetic cost of moving the limb. This study utilized peripheral quantitative computed tomography scanning to measure the trabecular mass in the lower and upper limb epiphyses of hominids, cercopithecines, and felids that are considered cursorial and non‐cursorial. One‐way ANOVA with Tukey post hoc corrections was used to test for significant differences in trabecular mass across limb epiphyses. The results indicate that overall, both cursors and non‐cursors exhibit varied trabecular mass in limb epiphyses and, in certain instances, conform to a proximal–distal decrease in mass irrespective of cursoriality. Specifically, hominid and cercopithecine hind limb epiphyses exhibit a proximal–distal decrease in mass irrespective of cursorial adaptations. These results suggest that cursorial mammals employ other energy saving mechanisms to minimize energy costs during running. Anat Rec, 298:797–809, 2015. © 2014 Wiley Periodicals, Inc.
Sequential design for achieving estimated accuracy of global sensitivities
Authors: Guenther John , Lee Herbert K. H. , Gray Genetha A.
Published: November 2014

Global sensitivity analysis provides information on the relative importance of the input variables for simulator functions used in computer experiments. It is more conclusive than screening methods for determining if a variable is influential, especially if a variable's influence is derived from its interactions with other variables. In this paper, we develop a method for providing global sensitivities with estimated accuracy. A treed Gaussian process serves as a statistical emulator of the black box function. A sequential experimental design makes effective and efficient use of simulator evaluations by adaptively sampling points that are expected to provide the maximum improvement to the emulator model. The method accounts for both sampling error and emulator error. Copyright © 2014 John Wiley & Sons, Ltd.
Lesson study practices in the development of secondary teaching of students with moderate learning difficulties: a systematic qualitative analysis in relation to context and outcomes
Authors: Norwich Brahm , Ylonen Annamari
Published: November 2014

This paper examines data from the novel use of Lesson Study (LS), an internationally known strategy for professional development, to improve the teaching of students (11–14 years old) with moderate learning difficulties (MLD). The paper aims to use a systematic qualitative analytic approach to identify variations in LS practice in a development and research project with about 100 teachers across 30 schools in two LS phases. It also examines the extent to which the immediate context of undertaking the LSs relates to the LS practices and the outcomes for teachers and learners. Different data sources were used to examine the LS context, LS practices and outcomes. Analysis showed how teachers adapted the LS strategy to their particular subject areas, the needs of students identified with MLD and their teaching contexts, while mainly keeping to the expected LS procedures. Co‐variation analysis showed how the degree to which contexts were supportive of LS could be related to student learning gains and teacher outcomes, but no mediating factors were identified. The conclusions indicate the importance of context for successful LS use. The findings are discussed in terms of possible mediating factors to better understand what is involved in quality and effective LS.
Quantitative analysis of chemotaxis towards toluene by Pseudomonas putida in a convection‐free microfluidic device
Authors: Wang Xiaopu , Atencia Javier , Ford Roseanne M.
Published: November 2014

Chemotaxis has been shown to be beneficial for the migration of soil‐inhabiting bacteria towards industrial chemical pollutants, which they degrade. Many studies have demonstrated the importance of this microbial property under various circumstances; however, few quantitative analyses have been undertaken to measure the two essential parameters that characterize the chemotaxis of bioremediation bacteria: the chemotactic sensitivity coefficient and the chemotactic receptor constant Kc. The main challenge to determine these parameters is that and Kc are coupled together in non‐linear mathematical models used to evaluate them. In this study we developed a method to accurately measure these parameters for Pseudomonas putida in the presence of toluene, an important pollutant in groundwater contamination. Our approach uses a multilayer microfluidic device to expose bacteria to a convection‐free linear chemical gradient of toluene that is stable over time. The bacterial distribution within the gradient is measured in terms of fluorescence intensity, and is then used to fit the parameters Kc and with mathematical models. Critically, bacterial distributions under chemical gradients at two different concentrations were used to solve for both parameters independently. To validate the approach, the chemotaxis parameters of Escherichia coli strains towards α‐methylaspartate were experimentally derived and were found to be consistent with published results from related work. Biotechnol. Bioeng. 2015;112: 896–904. © 2014 Wiley Periodicals, Inc.
SSDesign: Computational metabolic pathway design based on flux variability using elementary flux modes
Authors: Toya Yoshihiro , Shiraki Takanori , Shimizu Hiroshi
Published: November 2014

Metabolic pathway modification based on the stoichiometric model has been an effective approach for enhancing microbial bio‐production. The network of optimal pathways for “growth‐associated” and “non‐growth‐associated” production can be designed from the flux variability (solution space). The present study introduces a new computational method (solution space design [SSDesign]) that visually designs the gene knockout solution space. The smallest reaction sets that satisfy the mass balances of intermediates are called elementary flux nodes (EFMs). Because some of the EFMs necessarily occupy the outer boundary nodes of the flux solution space, the proposed SSDesign determines the area over which EFMs should be removed from the solution space of the parent strain, and explores the gene knockouts that will eliminate these undesirable EFMs. To evaluate the performance of SSDesign, the model was applied to growth‐associated and non‐growth‐associated succinate production in Escherichia coli. In the growth‐associated case, the deletion mutants that promoted succinate production at maximum biomass yield were predicted, and a candidate of ΔptsG ΔpykA,F ΔpflA has been experimentally confirmed as a succinate producer. Simply by changing the parameters, the gene knockout combinations yielding high growth yield were successfully predicted by SSDesign. In the non‐growth‐associated case, strong candidates for succinate production were the deletion mutants ΔpntAB ΔsfcA ΔpykA,F and ΔsfcA ΔmaeB ΔpykA,F Δzwf. According to the solution spaces, these strains allow high growth yield and inevitably produce succinate at zero biomass yield, since their metabolic pathways cannot sustain steady‐state without discarding succinate from the cell. Biotechnol. Bioeng. 2015;112: 759–768. © 2014 Wiley Periodicals, Inc.
Present and Future of Cyclopropanations in Fragrance Chemistry
Authors: Schröder Fridtjof
Published: November 2014

The elaboration of new cyclopropanation methods is expected to make selectively new Δ‐compounds available, either as precursors or as new ingredients with superior olfactory impacts. The improvement of cyclopropanation processes through understanding of reaction mechanisms reduces costs and environmental impact. Givaudan is the leading ‘Flavor & Frangrance’ company which successfully brings Δ‐molecules to the market. Javanol®, for example, with its unique performance exemplifies the product of an efficient industrial cyclopropanation of a dienol precursor. Serenolide®, Toscanol®, and Pashminol® are other high‐impact Δ‐fragrance ingredients manufactured at Givaudan. This review describes our journey from advanced SimmonsSmith methodology using Zn carbenoids, to Al‐ and Mg‐mediated cyclopropanation techniques in the context of related alternative cyclopropanation methods for the transfer of the CH2 group onto CC bonds. The resulting cyclopropane products are themselves interesting substrates for further transformation to other flavor and fragrance compounds.

Throughout this Review, the notation Δ refers to the presence of a cyclopropane ring, i.e., a ‘Δ‐compound’ is defined as a compound that contains a cyclopropyl substituent or a ‘fused cyclopropa’ component, or a ‘spiro‐cyclopropane’ moiety.
Synthesis and Sensory Studies of Umami‐Active Scaffolds
Authors: Backes Michael , Paetz Susanne , Vössing Tobias , Ley Jakob Peter
Published: November 2014

The class of 2‐isopropyl‐5‐methylbicyclo[4.1.0]heptane‐7‐carboxamides, 1–4, has been identified as potent umami‐tasting molecules. A scalable synthesis of this challenging scaffold and new sensory insights will be presented. Interestingly, the umami characteristics differ remarkably, depending on constitutional and stereochemical features of the parent scaffold. During our studies, we could identify the carboxamide moiety as a crucial factor to influence the umami intensity of these scaffolds. In addition, the configuration of the cyclopropyl moiety exerts some influence, whereas the absolute configuration of the menthyl scaffold, at least the tested D‐ and L‐configuration, is less important.
Synthesis, Crystal Structure, and Biological Activities of Two Chiral Mononuclear Mn(III) Complexes
Authors: Wang Bi‐Wei , Jiang Lin , Shu Si‐Sheng , Li Bo‐Wen , Dong Zhang , Gu Wen , Liu Xin , Tian Jin‐Lei
Published: November 2014

Two new chiral mononuclear Mn(III) complexes, [MnL(R)Cl (C2H5OH)]•C2H5OH (1) and [MnL(S) (CH3OH)2]Cl•CH3OH (2), {H2L = (R,R)‐or (S,S)‐N,N’‐bis‐(2‐hydroxy‐1‐naphthalidehydene)‐cyclohexanediamine} were synthesized and characterized by various physicochemical techniques. Bond valence sum (BVS) calculations and the Jahn‐Teller effect indicate that the Mn centers are in a +3 oxidation state. The statuses of the two complexes in the solution were confirmed as a pair of enantiomers by electrospray ionization, mass spectrometry (ESI‐MS) spectrum. The binding ability of the complexes with calf thymus CT‐DNA was investigated by spectroscopic and viscosity measurements. Both of the complexes could interact with CT‐DNA via an intercalative mode with the order of 1 (R‐enantiomer) >2 (S‐enantiomer). Under the physiological conditions, the two compounds exhibit efficient DNA cleavage activities without any external agent, which also follows the order of R‐enantiomer > S‐enantiomer. Interestingly, the concentration‐dependent DNA cleavage experiments indicate an optimal concentration of 17.5 μM. In addition, the interaction of the compounds with bovine serum albumin (BSA) was also investigated, which indicated that the complexes could quench the intrinsic fluorescence of BSA by a static quenching mechanism. Chirality 27:142‐150, 2015. © 2014 Wiley Periodicals, Inc.
Interaction between Microbes DNA and Atrazine in Black Soil Analyzed by Spectroscopy
Authors: Zhang Ying , Wang Zhigang , Guo Huosheng , Meng Dongfang , Wang Yang , Wong Po‐keung
Published: November 2014

It could be shown that atrazine bound to microbes DNA in black soil by using ethidium bromide (EB) as a fluorescence probe. To study the interaction between atrazine and the microbes DNA in black soil, spectral absorption and fluorescence analysis were adopted. Atrazine, when bound to DNA, showed a hyperchromic and red shift in the absorption spectra and fluorescence quenching (>50%) in the fluorescence spectra, which indicated the intercalation. The effect of phosphate ion showed that there were electrostatic attractions with the anionic sugar‐phosphate backbone of DNA. The ratio plots “fluorescence intensities in the absence” to “fluorescence intensities in the presence of a quencher” (Fo/F) showed that the quenching of fluorescence by atrazine was a combined quenching process. The results indicated that there were two binding modes, intercalation and electrostatic attractions, happened simultaneously. The hyperchromicity in the absorption spectra indicated the breaking or denaturation of DNA, and a fluorescence inhibiting effect showed that atrazine had a high ability to bind to the DNA of black soil microbes. Based on these results, it was speculated that the binding between atrazine and the DNA the black soil microbes could inhibit some functions of the nucleic acid, restrain microbial activity or cause genotoxicity.
Dimethyl Phthalate Degradation by UV/H2O2: Combination of Experimental Methods and Quantum Chemical Calculation
Authors: Du Er‐Deng , Feng Xin‐Xin , Guo Ying‐Qing , Peng Ming‐Guo , Feng Hong‐Qi , Wang Juan‐Lin , Zhang Shuo
Published: November 2014

Photochemical degradation of typical phthalate esters, as, e.g. dimethyl phthalate (DMP), in water by the UV/H2O2 process was investigated. The degradation rate of DMP was affected by several reaction factors, including initial DMP concentration, H2O2 concentration, UV light intensity, and coexisting cations and anions. The DMP degradation rate decreased with increasing initial DMP concentration. Carbonate ions significantly reduced the reaction rate by 70.2%, while the degradation rate was improved ten‐fold in the presence of ferric ions. The initial reaction mechanism and possible degradation products were investigated using density functional theory (DFT), including B3LYP and M062X hybrid functional. The addition of OH radicals (OH•) to the C4 position of the DMP ring is energetically favored for the initial reaction of DMP with OH•. Dimethyl 4‐hydroxyphthalate (DMP‐4OH) is one of the initial degradation intermediates. A possible reaction mechanism was also proposed based on GC/MS analysis and quantum chemical calculations. The formation of DMP‐4OH has been explained by quantum chemical calculations, which indicates the advantage and promising role of this method in the degradation mechanism analysis.
Introducing Wpt (Waypoint): A color equivalency representation for defining a material adjustment transform
Authors: Derhak Maxim W. , Berns Roy S.
Published: November 2014

The basis of this research is the manipulation of sensor excitation values to account for differences in observer or illuminant when spectral data are unknown. This touches on several related topics: color constancy, chromatic adaptation, and white balancing. The central premise is that these concepts make use of some form of intermediate color equivalency representation or waypoint system that makes comparison and color transformations possible. Differences between these concepts are related to the kind of color equivalency representation system used and how transformations are made into and out of it. A new sensor excitation normalization method was derived that has been optimized to predict changes in material color as Wpt (pronounced Waypoint) coordinates, which can be used to form a material adjustment transform. The prediction of such changes is also known as least dissimilar color matching. This is contrasted with a chromatic adaptation transform, which is optimized to predict corresponding color changes. As such a distinction is made between adaptation (which is based on corresponding color) and adjustment (which is based on other criteria). © 2014 Wiley Periodicals, Inc. Col Res Appl, 40, 535–549, 2015
The dynein inhibitor Ciliobrevin D inhibits the bidirectional transport of organelles along sensory axons and impairs NGF‐mediated regulation of growth cones and axon branches
Authors: Sainath Rajiv , Gallo Gianluca
Published: November 2014

The axonal transport of organelles is critical for the development, maintenance, and survival of neurons, and its dysfunction has been implicated in several neurodegenerative diseases. Retrograde axon transport is mediated by the motor protein dynein. In this study, using embryonic chicken dorsal root ganglion neurons, we investigate the effects of Ciliobrevin D, a pharmacological dynein inhibitor, on the transport of axonal organelles, axon extension, nerve growth factor (NGF)‐induced branching and growth cone expansion, and axon thinning in response to actin filament depolymerization. Live imaging of mitochondria, lysosomes, and Golgi‐derived vesicles in axons revealed that both the retrograde and anterograde transport of these organelles was inhibited by treatment with Ciliobrevin D. Treatment with Ciliobrevin D reversibly inhibits axon extension and transport, with effects detectable within the first 20 min of treatment. NGF induces growth cone expansion, axonal filopodia formation and branching. Ciliobrevin D prevented NGF‐induced formation of axonal filopodia and branching but not growth cone expansion. Finally, we report that the retrograde reorganization of the axonal cytoplasm which occurs on actin filament depolymerization is inhibited by treatment with Ciliobrevin D, indicating a role for microtubule based transport in this process, as well as Ciliobrevin D accelerating Wallerian degeneration. This study identifies Ciliobrevin D as an inhibitor of the bidirectional transport of multiple axonal organelles, indicating this drug may be a valuable tool for both the study of dynein function and a first pass analysis of the role of axonal transport. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 757–777, 2015
Filter‐Based Short‐Term Electric Load Prediction Considering Characteristics of Load Curve
Authors: Namerikawa Toru , Hosoda Yasuhiko
Published: November 2014

This paper deals with filter‐based short‐term electric load prediction taking into consideration the characteristics of the load curve. We propose a predictive method to forecast the future electric load demand for 36 h from 12:00 PM, and evaluate the peak and bottom of the load curves on the next day. We propose a load model, estimate the unknown parameters of the model by means of an filter using the data separated for nonworking days and weekdays, with the same pattern of the previous data chosen and assigned to the model parameters. The simulation results show the effectiveness of the proposed prediction methodology.
Rubbing Detection of Sliding Bearings in Early Stage by Frequency Modulation Analysis
Authors: Sako Takashi , Tokumo Koutaro , Yoshie Osamu
Published: November 2014

It is important in maintenance to detect rubbing of sliding bearings in the early stage. An experiment on mild rubbing conditions was conducted, and the changes in vibration were examined. Importantly, a newly found fact is that peaks in the spectral domain with respect to the rotational period occur as a result of rubbing. Consequently, cepstrum analysis was shown to be effective for the detection of rubbing in the early stage. A device that can follow the level of the quefrency was developed based upon this idea. Utilizing the device is a highly efficient way to monitor the condition of a sliding bearing.
Mathematical Analysis of Manufacturing Lead Time: Applications to Deadline Scheduling in Manufacturing Systems
Authors: Shirai Kenji , Amano Yoshinori
Published: November 2014

In this paper, we apply a stochastic differential equation (SDE) as a mathematical model that describes the manufacturing process from input of materials to the end of the process. We utilize the risk‐neutral principle in stochastic calculus based on the SDE. We extend the mathematical model to allow for objective evaluation. In order to improve the lead time in a manufacturing process, we introduce an evaluation equation that satisfies a certain compatibility constraint with respect to the lead time; this compatibility constraint with lead time refers to a strategy that eliminates irrelevant processes from the overall process, and results in improvements to the process. We assume a probability density function of log‐normal type, which is the probability density function from the input materials to the end of the process. The present paper evaluates a certain compatibility constraint with lead time by applying risk neutrality and the martingale measure of the stochastic integral under this assumption. After the evaluation value is calculated by the evaluation equation, a process control system evaluates each subprocess and performs rescheduling to improve the utilization efficiency of the entire manufacturing process. Thus, a front‐end process is used to cancel requests to the process, and follows the instructions in the process control systems. However, the present paper gives only a simulation evaluation in which the parameters are calculated, and does not discuss compatibility between an evaluation value based on the calculated manufacturing lead time compatibility constraint and a real system. However, the paper offers an idea for finding bottleneck subprocesses in a manufacturing process, and for use as a software tool for process synchronization.
Status of Soft Contact Lens Biosensor Development for Tear Sugar Monitoring: A Review
Authors: Kudo Hiroyuki , Arakawa Takahiro , Mitsubayashi Kohji
Published: November 2014

Noninvasive and continuous glucose monitoring is of increasing significance since diabetes mellitus has become a global problem, not only in developed countries. Usually, continuous glucose monitors use the relationship between blood glucose and other body fluids. In particular, we focused on the relationship between blood glucose and tear glucose. A soft contact lens (SCL) biosensor has been developed for the assessment of blood glucose by real‐time tear sugar monitoring. The SCL biosensor has film electrodes on the rounded surface of a polydimethyl siloxane (PDMS) contact lens, and glucose oxidase (GOD) is immobilized on the sensing region of the electrodes. In this paper, the status of SCL biosensor development and the application of the SCL biosensor in the real‐time monitoring of tear glucose are reviewed.
N‐Substituted Glycines with Functional Side‐Chains for Peptoid Synthesis
Authors: René Adeline , Martinez Jean , Cavelier Florine
Published: November 2014

N‐Substituted glycines (NSG) constitute mimics of natural amino acids, and bring stability to peptide analogues. We developed a method to synthesize NSG bearing reactive secondary heterofunctionality. It was shown that persilylation could be used for temporary protection of reactive groups present on the substrate, with the aim of selectively alkylating the amine groups. NSG ready for peptide coupling were obtained by C‐terminal deprotection and N‐terminal protection of the resulting amino acid derivatives. This method was applied to prepare N‐alkylated glycines as analogues of serine, cysteine, tyrosine and tryptophan. The last two derivatives were obtained in good yields and N‐homotyrosine (N‐hTyr) has been introduced into a peptide sequence of interest using automated solid‐phase peptide synthesis (SPPS).
Separation mechanisms for palonosetron stereoisomers at different chiral selector concentrations in MEKC
Authors: Hu Shao‐Qiang , Guo Xu‐Ming , Shi Hai‐Jun , Luo Rong‐Jie
Published: November 2014

The separation mechanisms for palonosetron (PALO) stereoisomers in MEKC using sodium cholate (SC) as surfactant and chiral selector have been studied, in a wide range of concentrations below and above the CMC. It was found that SC micelles only provide chirally selective recognition for 3a carbon chiral center in PALO molecules. The resolution of the configurations of 2 carbon chiral center is achieved by the difference of mobility in continuous phase. A schematic diagram depicting the separation mechanisms and the corresponding migration orders among all of four stereoisomers was proposed based on the measured separation parameters. A MEKC method to achieve the complete separation of four stereoisomers in very short time using a very low chiral selector concentration, instead of high concentrations generally considered, was developed based on the understanding of the mechanisms.
Global properties and propensity to dimerization of the amyloid‐beta (12–28) peptide fragment through the modeling of its monomer and dimer diffusion coefficients and electrophoretic mobilities
Authors: Deiber Julio A. , Peirotti Marta B. , Piaggio Maria V.
Published: November 2014

Neuronal activity loss may be due to toxicity caused mainly by amyloid‐beta (1–40) and (1–42) peptides forming soluble oligomers. Here the amyloid‐beta (12–28) peptide fragment (monomer) and its dimer are characterized at low pH through the modeling of their diffusion coefficients and effective electrophoretic mobilities. Translational diffusion coefficient experimental values of monomer and dimer analogs of this peptide fragment and monomer and dimer mixtures at thermodynamic equilibrium are used as reported in the literature for different monomer initial concentrations. The resulting electrokinetic and hydrodynamic global properties are employed to evaluate the amyloid‐beta (12–28) peptide fragment propensity to dimerization through a thermodynamic theoretical framework. Therefore equilibrium constants are considered at pH 2.9 to elucidate one of the amyloidogenic mechanisms involving the central hydrophobic region LVFFA of the peptide spanning residues 17–21 associated with phenylalanine at positions 19 and 20 in the amino acid sequence of amyloid‐beta peptides. An analysis demonstrating that peptide aggregation is a concentration‐dependent process is provided, where both pair and intraparticle charge regulation phenomena become relevant. It is shown that the modeling of the effective electrophoretic mobility of the amyloid‐beta (12–28) peptide fragment is crucial to understand the effect of hydrophobic region LVFFA in the amyloidogenic process.
Sedimentary effects of flood‐producing windstorms in playa lakes and their role in the movement of large rocks
Authors: Sanz‐Montero M. E. , Cabestrero Ó. , Rodríguez‐Aranda J. P.
Published: November 2014

This paper sheds light on the hydrodynamic conditions of transport and sedimentary effects of wind‐induced water currents produced during strong windstorms in low gradient systems. Repeated field surveys were conducted in a playa lake in central Spain to determine the impacts of major winter storms on the bed form morphology in real time. The succession of storms that passed through the area from mid‐December 2013 to early February 2014 left behind a variety of sedimentary structures: mainly ripple marks showing complex patterns and erosional structures. The latter include obstacle scours, grooves and other tool marks. In situ observations revealed that strong storm events in almost flat, extremely shallow lakes (less than 5 cm) have enough hydraulic energy to erode and remove high volumes of sediments and may also lead to large stones sliding across the bed, thus creating long grooves.

Sole marks found in ancient continental successions have been typically attributed to fluvial conditions. We suggest that shallow lake basins should not be discounted when storm‐generated structures are preserved in ancient rocks. The identification of such sedimentary structures provides valuable information for reconstructing hydrodynamic conditions and paleoclimatic conditions in semi‐arid environments. Copyright © 2014 John Wiley & Sons, Ltd.
Isomeric ent‐Labdane‐Type Diterpenoids from the Stems of Rhizophora mucronata
Authors: Madhu Ankireddy , Suresh Chandra Venkata Appa Rao Annam , Sushma Sukki , Mangala Gowri Ponnapalli , Venugopal Raju Tuniki
Published: November 2014

Two new constitutional isomers of ent‐labdane‐type diterpenoids, 1 and 2, with an unusual seven‐membered lactone moiety (i.e., 1), together with two known compounds, 3 and 4, were isolated from the acetone extract of Rhizophora mucronata. Their structures were elucidated as rhizomucronol A and B (1 and 2, resp.) by spectroscopic analyses and chemical evidence. The absolute configuration of 2 was established by applying the Mosher ester procedure.
Wnt‐3a‐activated human fibroblasts promote human keratinocyte proliferation and matrix destruction
Authors: Sobel Katrin , Tham Marius , Stark Hans‐Jürgen , Stammer Hermann , Prätzel‐Wunder Silke , Bickenbach Jackie R , Boukamp Petra
Published: November 2014

Aberrant Wnt regulation, detectable by nuclear translocation of beta‐catenin, is a hallmark of many cancers including skin squamous cell carcinomas (SCCs). By analyzing primary human skin SCCs, we demonstrate that nuclear beta‐catenin is not restricted to SCC cells but also detected in stromal fibroblasts, suggesting an important role for aberrant Wnt regulation also in the tumor microenvironment. When human keratinocytes and fibroblasts were treated with Wnt‐3a, fibroblasts proved to be more responsive. Accordingly, Wnt‐3a did not alter HaCaT cell functions in a cell‐autonomous manner. However, when organotypic cultures (OTCs) were treated with Wnt‐3a, HaCaT keratinocytes responded with increased proliferation. As nuclear beta‐catenin was induced only in the fibroblasts, this argued for a Wnt‐dependent, paracrine keratinocyte stimulation. Global gene expression analysis of Wnt‐3a‐stimulated fibroblasts identified genes encoding interleukin‐8 (IL‐8) and C‐C motif chemokine 2 (CCL‐2) as well as matrix metalloproteinase‐1 (MMP‐1) as Wnt‐3a targets. In agreement, we show that IL‐8 and CCL‐2 were secreted in high amounts by Wnt‐3a‐stimulated fibroblasts also in OTCs. The functional role of IL‐8 and CCL‐2 as keratinocyte growth regulators was confirmed by directly stimulating HaCaT cell proliferation in conventional cultures. Most important, neutralizing antibodies against IL‐8 and CCL‐2 abolished the Wnt‐dependent HaCaT cell hyperproliferation in OTCs. Additionally, MMP‐1 was expressed in high amounts in Wnt‐3a‐stimulated OTCs and degraded the stromal matrix. Thus, our data show that Wnt‐3a stimulates fibroblasts to secrete both keratinocyte proliferation‐inducing cytokines and stroma‐degrading metalloproteinases, thereby providing evidence for a novel Wnt deregulation in the tumor‐stroma directly contributing to skin cancer progression.
Renal cell carcinomas of chronic kidney disease patients harbor the mutational signature of carcinogenic aristolochic acid
Authors: Jelaković Bojan , Castells Xavier , Tomić Karla , Ardin Maude , Karanović Sandra , Zavadil Jiri
Published: November 2014

Aristolochic acid (AA) is a potent dietary cytotoxin and carcinogen, and an established etiological agent underlying severe human nephropathies and associated upper urinary tract urothelial cancers, collectively designated aristolochic acid nephropathy (AAN). Its genome‐wide mutational signature, marked by predominant A:T > T:A transversions occurring in the 5′‐CpApG‐3′ trinucleotide context and enriched on the nontranscribed gene strand, has been identified in human upper urinary tract urothelial carcinomas from East Asian patients and in experimental systems. Here we report a whole‐exome sequencing screen performed on DNA from formalin‐fixed, paraffin‐embedded renal cell carcinomas (RCC) arising in chronic renal disease patients from a Balkan endemic nephropathy (EN) region. In the EN regions, the disease results from the consumption of bread made from wheat contaminated by seeds of Aristolochia clematitis, an AA‐containing plant. In five of eight (62.5%) tested RCC tumor specimens, we observed the characteristic global mutational signature consistent with the mutagenic effects of AA. This signature was absent in the control RCC samples obtained from patients from a nonendemic, metropolitan region. By identifying a new tumor type associated with the AA‐driven genome‐wide mutagenic process in the context of renal disease, our results suggest new epidemiological and public health implications for the RCC incidence worldwide, particularly for the high‐risk regions with unregulated use of AA‐containing traditional herbal medicines.
Development of new non‐invasive tests for colorectal cancer screening: The relevance of information on adenoma detection
Authors: Haug Ulrike , Knudsen Amy B. , Lansdorp‐Vogelaar Iris , Kuntz Karen M.
Published: November 2014

Researchers are actively pursuing the development of a new non‐invasive test (NIT) for colorectal cancer (CRC) screening as an alternative to fecal occult blood tests (FOBTs). The majority of pilot studies focus on the detection of invasive CRC rather than precursor lesions (i.e., adenomas). We aimed to explore the relevance of adenoma detection for the viability of an NIT for CRC screening by considering a hypothetical test that does not detect adenomas beyond chance. We used the Simulation Model of Colorectal Cancer (SimCRC) to estimate the effectiveness of CRC screening and the lifetime costs (payers' perspective) for a cohort of US 50‐years‐old persons to whom CRC screening is offered from age 50–75. We compared annual screening with guaiac and immunochemical FOBTs (with sensitivities up to 70 and 24% for CRC and adenomas, respectively) to annual screening with a hypothetical NIT (sensitivity of 90% for CRC, no detection of adenomas beyond chance, specificity and cost similar to FOBTs). Screening with the NIT was not more effective, but was 29–44% more costly than screening with FOBTs. The findings were robust to varying the screening interval, the NIT's sensitivity for CRC, adherence rates favoring the NIT, and the NIT's unit cost. A comparative modelling approach using a model that assumes a shorter adenoma dwell time (MISCAN‐COLON) confirmed the superiority of the immunochemical FOBT over an NIT with no ability to detect adenomas. Information on adenoma detection is crucial to determine whether a new NIT is a viable alternative to FOBTs for CRC screening. Current evidence thus lacks an important piece of information to identify marker candidates that hold real promise and deserve further (large‐scale) evaluation.
A comprehensively characterized large panel of head and neck cancer patient‐derived xenografts identifies the mTOR inhibitor everolimus as potential new treatment option
Authors: Klinghammer Konrad , Raguse Jan‐Dirk , Plath Thomas , Albers Andreas E. , Joehrens Korinna , Zakarneh Andre , Brzezicha Bernadette , Wulf‐Goldenberg Annika , Keilholz Ulrich , Hoffmann Jens , Fichtner Iduna
Published: November 2014

Patient‐derived xenograft (PDX) models have shown to reflect original patient tumors better than any other preclinical model. We embarked in a study establishing a large panel of head and neck squamous cell carcinomas PDX for biomarker analysis and evaluation of established and novel compounds. Out of 115 transplanted specimens 52 models were established of which 29 were characterized for response to docetaxel, cetuximab, methotrexate, carboplatin, 5‐fluorouracil and everolimus. Further, tumors were subjected to sequencing analysis and gene expression profiling of selected mTOR pathway members. Most frequent response was observed for docetaxel and cetuximab. Responses to carboplatin, 5‐fluorouracil and methotrexate were moderate. Everolimus revealed activity in the majority of PDX. Mutational profiling and gene expression analysis did not reveal a predictive biomarker for everolimus even though by trend RPS6KB1 mRNA expression was associated with response. In conclusion we demonstrate a comprehensively characterized panel of head and neck cancer PDX models, which represent a valuable and renewable tissue resource for evaluation of novel compounds and associated biomarkers.
Markers of vitamin B6 status and metabolism as predictors of incident cancer: The Hordaland Health Study
Authors: Zuo Hui , Ueland Per M. , Eussen Simone J.P.M. , Tell Grethe S. , Vollset Stein E. , Nygård Ottar , Midttun Øivind , Meyer Klaus , Ulvik Arve
Published: November 2014

Dietary intake and/or circulating concentrations of vitamin B6 have been associated with risk of cancer, but results are inconsistent and mechanisms uncertain. Pyridoxal 5'‐phosphate (PLP) is the most commonly used marker of B6 status. We recently proposed the ratio 3‐hydroxykynurenine/xanthurenic acid (HK/XA) as an indicator of functional vitamin B6 status, and the 4‐pyridoxic acid (PA) /(pyridoxal (PL) +PLP) ratio (PAr) as a marker of vitamin B6 catabolism during inflammation. We compared plasma PLP, HK/XA and PAr as predictors of cancer incidence in a prospective community‐based cohort in Norway. This study included 6,539 adults without known cancer at baseline (1998–99) from the Hordaland Health Study (HUSK). HR and 95% CI were calculated for the risk of overall and site‐specific cancers using multivariate Cox proportional hazards regression with adjustment for potential confounders. After a median follow‐up time of 11.9 years, 963 cancer cases (501 men and 462 women) were identified. Multivariate‐adjusted Cox‐regression showed no significant relation of plasma PLP or HK/XA with risk of incident cancer. In contrast, PAr was significantly associated with risk of cancer with HR (95% CI) = 1.31 (1.12–1.52) per two standard deviation (SD) increment (p < 0.01). Further analysis showed that PAr was a particular strong predictor of lung cancer with HR (95% CI) = 2.46 (1.49–4.05) per two SD increment (p < 0.01). The present results indicate that associations of vitamin B6 with cancer may be related to increased catabolism of vitamin B6, in particular for lung cancer where inflammation may be largely involved in carcinogenesis.
An extended non‐local means algorithm: Application to brain MRI
Authors: Iftikhar Muhammad Aksam , Jalil Abdul , Rathore Saima , Ali Ahmad , Hussain Mutawarra
Published: November 2014

Improved adaptive nonlocal means (IANLM) is a variant of classical nonlocal means (NLM) denoising method based on adaptation of its search window size. In this article, an extended nonlocal means (XNLM) algorithm is proposed by adapting IANLM to Rician noise in images obtained by magnetic resonance (MR) imaging modality. Moreover, for improved denoising, a wavelet coefficient mixing procedure is used in XNLM to mix wavelet sub‐bands of two IANLM‐filtered images, which are obtained using different parameters of IANLM. Finally, XNLM includes a novel parameter‐free pixel preselection procedure for improving computational efficiency of the algorithm. The proposed algorithm is validated on T1‐weighted, T2‐weighted and Proton Density (PD) weighted simulated brain MR images (MRI) at several noise levels. Optimal values of different parameters of XNLM are obtained for each type of MRI sequence, and different variants are investigated to reveal the benefits of different extensions presented in this work. The proposed XNLM algorithm outperforms several contemporary denoising algorithms on all the tested MRI sequences, and preserves important pathological information more effectively. Quantitative and visual results show that XNLM outperforms several existing denoising techniques, preserves important pathological information more effectively, and is computationallyefficient.
Evaluation of polyvinyl alcohol cryogel as an acoustic coupling medium for low‐intensity transcranial focused ultrasound
Authors: Lee Wonhye , Lee Stephanie D. , Park Michael Y. , Yang Jaechun , Yoo Seung‐Schik
Published: November 2014

Transcranial focused ultrasound (FUS) has emerged as a noninvasive neuromodulatory modality with exquisite depth penetration and spatial selectivity. Liquids, such as degassed water or mineral oil, are used as acoustic coupling media between the ultrasound‐generating transducer and the brain; however, they require a separate container that limits the spatial orientation of the transducers with respect to the sonication target. Nonliquid, gel‐like materials that do not require a housing container have been sought after as coupling media to overcome such limitations. Polyvinyl alcohol (PVA), when dissolved in water and undergone freeze–thaw cycle(s), forms a flexible hydrogel having a high level of acoustic transmission. To examine the feasibility of the PVA cryogel as the coupling material for transcranial FUS, the mechanical properties (in terms of its Young's modulus) and acoustic attenuation of the PVA cryogel were examined using different concentrations and number of freeze–thaw cycles. The cryogel with 6 or 7% (w/v) concentrations and two freeze–thaw cycles showed minimum pressure attenuation (on the order of 1%) across the different ultrasound frequencies (250–650 kHz). The cryogel was molded to fit around a single‐element FUS transducer and was applied to a head phantom, showing the flexibility in orienting the sonication paths at different angles and depths. The use of the cryogel did not alter the location and shape of acoustic focal profile compared to the one measured in the degassed water. The present work suggests that PVA cryogel may be used as an alternative acoustic coupling medium for low‐intensity FUS applications.
A study of long‐term fMRI reproducibility using data‐driven analysis methods
Authors: Song Xiaomu , Panych Lawrence P. , Chou Ying‐Hui , Chen Nan‐Kuei
Published: November 2014

The reproducibility of functional magnetic resonance imaging (fMRI) is important for fMRI‐based neuroscience research and clinical applications. Previous studies show considerable variation in amplitude and spatial extent of fMRI activation across repeated sessions on individual subjects even using identical experimental paradigms and imaging conditions. Most existing fMRI reproducibility studies were typically limited by time duration and data analysis techniques. Particularly, the assessment of reproducibility is complicated by a fact that fMRI results may depend on data analysis techniques used in reproducibility studies. In this work, the long‐term fMRI reproducibility was investigated with a focus on the data analysis methods. Two spatial smoothing techniques, including a wavelet‐domain Bayesian method and the Gaussian smoothing, were evaluated in terms of their effects on the long‐term reproducibility. A multivariate support vector machine (SVM)‐based method was used to identify active voxels, and compared to a widely used general linear model (GLM)‐based method at the group level. The reproducibility study was performed using multisession fMRI data acquired from eight healthy adults over 1.5 years' period of time. Three regions‐of‐interest (ROI) related to a motor task were defined based upon which the long‐term reproducibility were examined. Experimental results indicate that different spatial smoothing techniques may lead to different reproducibility measures, and the wavelet‐based spatial smoothing and SVM‐based activation detection is a good combination for reproducibility studies. On the basis of the ROIs and multiple numerical criteria, we observed a moderate to substantial within‐subject long‐term reproducibility. A reasonable long‐term reproducibility was also observed from the inter‐subject study. It was found that the short‐term reproducibility is usually higher than the long‐term reproducibility. Furthermore, the results indicate that brain regions with high contrast‐to‐noise ratio do not necessarily exhibit high reproducibility. These findings may provide supportive information for optimal design/implementation of fMRI studies and data interpretation.