bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimode processes monitoring based on hierarchical mode division and subspace decomposition
Authors: Li Shuai , Zhou Xiaofeng , Shi Haibo , Pan Fucheng , Li Xin , Zhang Yichi
Published: February 2018

To handle multimodal uncertainty and dynamics which are common in actual industrial processes, this paper proposes a multimode process monitoring method based on hierarchical mode division and subspace decomposition. First, hierarchical mode division is presented to achieve hierarchical mode information for multimode process modelling, which can improve the adaptability of industrial processes with multimodal uncertainty. Then, hierarchical subspace decomposition is presented to decompose multimode processes into multiple global subspaces and multiple local subspaces for monitoring. Lastly, the most similar mode with various hierarchical modes at the current sampling point is dynamically determined for monitoring, which considers multimodal dynamics. The simulation tests of the penicillin fermentation processes are developed to show feasibility and superiority of the proposed method.
A learning‐based approach for virtual machine placement in cloud data centers
Authors: Ghobaei‐Arani Mostafa , Rahmanian Ali Asghar , Shamsi Mahboubeh , Rasouli‐Kenari Abdolreza
Published: February 2018

In recent years, the increasing use of cloud services has led to the growth and importance of developing cloud data centers. One of the challenging issues in the cloud environments is high energy consumption in data centers, which has been ignored in the corporate competition for developing cloud data centers. The most important problems of using large cloud data centers are high energy costs and greenhouse gas emission. So, researchers are now struggling to find an effective approach to decreasing energy consumption in cloud data centers. One of the preferred techniques for reducing energy consumption is the virtual machines (VMs) placement. In this paper, we present a VM allocation algorithm to reduce energy consumption and Service Level Agreement Violation (SLAV). The proposed algorithm is based on best‐fit decreasing algorithm, which uses learning automata theory, correlation coefficient, and ensemble prediction algorithm to make better decisions in VM allocation. The experimental results indicated improvement regarding energy consumption and SLAV, compared with well‐familiar baseline VM allocation algorithms.
Is cortisol production in response to an acute stressor associated with diurnal cortisol production during adolescence?
Authors: Lucas‐Thompson Rachel G. , Henry Kimberly L. , McKernan Charlotte J.
Published: February 2018

The goal of the current study was to examine the extent to which cortisol responding to an acute stressor is related to diurnal cortisol patterns during adolescence. Participants were 105 adolescents (10–17 years of age) who experienced a robust social‐evaluative stressor and provided saliva samples (before and immediately after, as well as 10, 20, and 30 min after the stressor) to assess both cortisol reactivity and recovery and also provided saliva samples (at wake‐up, 30 min after wake‐up, 4 pm, and at bedtime) on two consecutive days to measure diurnal cortisol production. Dual process latent growth curve models, one for cortisol reactivity and one for diurnal cortisol, indicated that dampened cortisol reactivity and prolonged cortisol recovery (i.e., less cortisol produced during reactivity but more cortisol produced during recovery) were associated with dampened decreases in cortisol production across the day, suggesting that adolescents are likely to show attenuation in multiple components of HPA axis functioning.
Cortical thickness patterns as state biomarker of anorexia nervosa
Authors: Lavagnino Luca , Mwangi Benson , Cao Bo , Shott Megan E. , Soares Jair C. , Frank Guido K. W.
Published: February 2018

Objective

Only few studies have investigated cortical thickness in anorexia nervosa (AN), and it is unclear whether patterns of altered cortical thickness can be identified as biomarkers for AN.

Method

Cortical thickness was measured in 19 adult women with restricting‐type AN, 24 individuals recovered from restricting‐type AN (REC‐AN) and 24 healthy controls. Those individuals with current or recovered from AN had previously shown altered regional cortical volumes across orbitofrontal cortex and insula. A linear relevance vector machine‐learning algorithm estimated patterns of regional thickness across 24 subdivisions of those regions.

Results

Region‐based analysis showed higher cortical thickness in AN and REC‐AN, compared to controls, in the right medial orbital (olfactory) sulcus, and greater cortical thickness for short insular gyri in REC‐AN versus controls bilaterally. The machine‐learning algorithm identified a pattern of relatively higher right orbital, right insular and left middle frontal cortical thickness, but lower left orbital, right middle and inferior frontal, and bilateral superior frontal cortical thickness specific to AN versus controls (74% specificity and 74% sensitivity, χ2 p < .004); predicted probabilities differed significantly between AN and controls (p < .023). No pattern significantly distinguished the REC‐AN group from controls.

Conclusions

Higher cortical thickness in medial orbitofrontal cortex and insula probably contributes to higher gray matter volume in AN in those regions. The machine‐learning algorithm identified a mixed pattern of mostly higher orbital and insular, but relatively lower superior frontal cortical thickness in individuals with current AN. These novel results suggest that regional cortical thickness patterns could be state markers for AN.
A hidden cost of migration? Innate immune function versus antioxidant defense
Authors: Eikenaar Cas , Isaksson Caroline , Hegemann Arne
Published: February 2018

Migration is energetically demanding and physiologically challenging. Migrating birds, for example, need to boost their antioxidant defenses to defeat the pro‐oxidants produced during high energetic activity. The enhanced antioxidant defense possibly withdraws limited resources (e.g., energy or micronutrients) from other physiological functions, such as immune defense. Such a trade‐off might not occur outside the migration seasons or in resident individuals. Here, we investigate whether there is a negative relationship between innate immune function and antioxidant defense by sampling both migrating and resident blackbirds (Turdus merula) at the same location during the same period of the annual cycle. We show that in migrating blackbirds microbial killing capacity (BKA), an integrative measure of baseline innate immune function was negatively correlated with total nonenzymatic antioxidant capacity. In contrast, in resident conspecifics, sampled at the same time and location, these two physiological measures were not correlated. This suggests that migrating birds trade off innate immune function and antioxidant defense. Furthermore, and likely a consequence of this trade‐off, in migrant blackbirds BKA was positively correlated with oxidative damage to lipids. In resident blackbirds BKA and degree of lipid oxidation were uncorrelated. The mechanism and currencies of the supposed trade‐off are currently unknown, but energetic investments or micronutrients are likely candidates. Future experimental studies could provide more conclusive evidence for this trade‐off; yet, our results open up a new level of thinking about the physiological costs of migration.
Environmental filtering and dispersal as drivers of metacommunity composition: complex spider webs as habitat patches
Authors: Fernandez‐Fournier Philippe , Avilés Leticia
Published: February 2018

Metacommunity theory has advanced the understanding of the patterns and processes shaping community structure at multiple scales. Various models have been put forward to explain the relative effects of environmental filtering, dispersal, and species traits on community composition. Here, we focus on complex, three‐dimensional webs of two social and two solitary spider species as habitat patches for associated communities of arthropods in a tropical rainforest in Ecuador. We used variance partitioning, constrained ordination, coherence analyses, and a colonization experiment to assess the role of environmental filtering and dispersal in this system. We found that the composition of communities associated with the four host species was mostly differentiated along two ordination axes, with the first axis roughly corresponding to level of sociality (solitary vs. social) and the other to web size. Associate abundance increased, but their density per unit volume decreased with host web size for all host species. Webs of social spider species had more variable communities and proportionally more aggressive (i.e., predatory) associates. After rarefaction to control for larger samples in larger webs, only one of the species showed a significant increase of species richness as a function of web size. The relatively quick colonization of experimentally established webs suggests high dispersal of more generalist species, but their lower proportion in older webs provides some evidence of a colonization–competition trade‐off at longer temporal scales. The distinctness of the communities associated with the four host species, and the eventual change in proportion of associates in newly founded vs. old webs, despite high dispersal, is consistent with environmental filtering and species traits playing a major role in determining patterns of species distribution in this system.
Versatile Click Cyanine Amino Acid Conjugates Showing One‐Atom‐Influenced Recognition of DNA/RNA Secondary Structure and Mitochondrial Localisation in Living Cells
Authors: Šmidlehner Tamara , Kurutos Atanas , Slade Jakov , Belužić Robert , Ang Dale L. , Rodger Alison , Piantanida Ivo
Published: February 2018

By a simple click CuAAC (copper(I)‐catalysed azide alkyne cycloaddition) procedure several cyanine dye analogues have been attached to the side‐chain of an amino acid to yield chromophore amino acid conjugates with the potential to fluoresce upon binding to a target. Due to the availabiltiy of the amino acid C and N termini for peptide coupling, these conjugates are suitable for easy incorporation into the backbone of peptides. The novel amino acid dyes prepared in this work, although intrinsically non‐fluorescent, gave rise to strong fluorimetric responses upon binding to double‐stranded (ds) DNA or RNA, the emission response to various polynucleotide secondary structures being controlled either by linker length or a halogen atom located on the cyanine part of the molecule. Molecular modelling confirmed the mode of binding to different polynucleotides, which was responsible for the recognition. Interestingly, cell localisation experiments showed that the dyes were specifically localised in mitochondria at variance with the localisation of the parent dyes, which accumulate in cell nuclei, which suggests that the amino acid tail (containing a triazole ring) might function as a novel mitochondria‐directing appendage.
l‐Menthol‐Assisted Synthesis of P‐Stereogenic Phosphinous Acid Amides and Phosphine‐Boranes
Authors: Włodarczyk Adam , Kozioł Anna E. , Stankevič Marek
Published: February 2018

Diastereomerically pure phenylphosphonous acid‐borane l‐menthyl ester N,N‐diethylamide was obtained through the fractional crystallization of a diastereomeric mixture of compounds synthesized from PhPCl2, l‐menthol, diethylamine, and BH3·THF. Treatment of racemic or diastereomerically pure phenylphosphonous acid‐borane derivatives with sodium in liquid ammonia followed by the addition of an electrophile led to the formation of phosphinous acid‐amides. Surprisingly, these compounds undergo preferential P–N bond cleavage under Birch reduction conditions.
Light‐emitting Diode‐assisted Determination of 2‐(1,1‐Dimethylethyl)‐1,4‐Benzenediol in Cosmetic Samples Exploiting TiO2 Sensitized with Lithium 7,7′,8,8′‐Tetracyanoquinodimethanide
Authors: Oliveira Monteiro Thatyara , Costa dos Santos Clenilton , Santos Damos Flávio , de Cássia Silva Luz Rita
Published: February 2018

This paper reports a novel analytical device for the determination of 2‐(1,1‐dimethylethyl)‐1,4‐benzenediol antioxidant (TBHQ) in cosmetic samples exploiting a photoelectrochemical sensor based on titanium dioxide nanoparticles sensitized with lithium 7,7′,8,8′‐tetracyanoquinodimethanide on indium tin oxide electrode. The proposed photoelectrochemical sensor possesses the capacity of harvesting light energy from a commercial light‐emitting diode (LED) lamp for the determination of TBHQ molecules. The photoelectrochemical sensor presented photocurrent response to antioxidant about 2‐fold higher than pure titanium dioxide. The sensor shows high photocurrent response to TBHQ antioxidant in comparison to photocurrent response to 2,3‐t‐butyl‐4‐hydroxyanisole and 2,6‐Di‐tert‐butyl‐4‐methylphenol, indicating selectivity to TBHQ. Under optimized experimental conditions, the photoelectrochemical sensor presents two linear ranges of response for the analyte, the former from 0.6 to 200 μmol L−1, and the latter from 200 to 5000 μmol L−1. A low limit of detection of 0.17 μmol L−1 was obtained for the proposed photoelectrochemical sensor. The sensor was successfully employed to the analysis of cosmetic samples, with recovery values between 96 % and 98 %.
Electrochemical DNA Biosensor Based on Magnetite/Multiwalled Carbon Nanotubes/Chitosan Nanocomposite for Bacillus Cereus Detection of Potential Marker for Gold Prospecting
Authors: Zuo Limei , Qu Qing , Li Lei , Ran Xin , Gui Jingwei , Wang Qiang , Cui Xinhua , Jiang Changliang
Published: February 2018

A label‐free DNA biosensor based on magnetite/multiwalled carbon nanotubes/chitosan (Fe3O4/MWCNTs‐COOH/CS) nanomaterial for detection of Bacillus cereus DNA sequences was fabricated. Negatively charged DNA was electrostatically adsorbed onto materials by protonation of positively charged chitosan under acidic conditions. The electrode surface and hybridization process were carried out by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). Under optimal conditions, the biosensor showed a good linear relationship between peak currents difference (ΔI) and logarithm of the target DNA concentration (Log C) ranging from 2.0×10−13 to 2.0×10−6 M with a detection limit of 2.0×10−15 M (signal/noise ratio of 3). The biosensor also revealed an excellent selectivity to three‐base, completely mismatched and completely matched DNA. This is a simple, fast and friendly method with a low detection limit for the detection of Bacillus cereus specific DNA compared with previously reported electrochemical DNA biosensor. Furthermore, the DNA biosensor may lead to the development of a technology for gold prospecting in the wild.
Effects of the liquid vapor oxygen transfer coefficient (kLα) on ethanol production from cassava residue and analysis of the fermentation kinetics
Authors: Li Xingjiang , Deng Yongdong , Wu Xuefeng , Yang Ying , Cao Lili , Yao Hongli , Mu Dongdong , Wang Hualin , Zheng Zhi , Jiang Shaotong
Published: February 2018

Cassava residue is the solid waste generated from the production of tapioca starch and has considerable reuse value. In this study, cassava residue was examined as a hydrolysate for ethanol production, and the effects of different liquid phase oxygen transfer coefficients (kLα) on the production of ethanol from cassava residue hydrolysates were studied. Based on analyses of dissolved oxygen and a set of optimal experimental schemes, dynamic models of cell growth and product synthesis were optimized, using MATLAB. When kLα was 85, fermentation was optimal; the ethanol titer reached 23.14 g L−1 at 72 h and cell growth reached 6.23 g L−1 at 96 h. Additionally, experiments were performed according to the dissolved oxygen curve obtained under these conditions. The resulting ethanol titer was 24.43 g L−1 (72 h) and the cell mass was 6.45 g L−1 (96 h).
Quantile estimators with orthogonal pinball loss function
Authors: Yu Lean , Yang Zebin , Tang Ling
Published: February 2018

To guarantee stable quantile estimations even for noisy data, a novel loss function and novel quantile estimators are developed, by introducing the effective concept of orthogonal loss considering the noise in both response and explanatory variables. In particular, the pinball loss used in classical quantile estimators is improved into novel orthogonal pinball loss (OPL) by replacing vertical loss by orthogonal loss. Accordingly, linear quantile regression (QR) and support vector machine quantile regression (SVMQR) can be respectively extended into novel OPL‐based QR and OPL‐based SVMQR models. The empirical study on 10 publicly available datasets statistically verifies the superiority of the two OPL‐based models over their respective original forms in terms of prediction accuracy and quantile property, especially for extreme quantiles. Furthermore, the novel OPL‐based SVMQR model with both OPL and artificial intelligence (AI) outperforms all benchmark models, which can be used as a promising quantile estimator, especially for noisy data.
Pt‐Sn‐Eu/C Catalysts: Application of Rare Earth Metals as Anodes in Direct Ethanol Fuel Cells
Authors: Corradini P. G. , Santos N. A. , Perez J.
Published: February 2018

Pt‐Sn‐Eu catalysts were synthesized by modified polyol method, evaluated for the ethanol oxidation reaction (EOR), and compared to commercial Pt/C and Pt‐Sn/C catalysts. The catalysts were electrochemically characterized in both three‐electrode and fuel cell setups. X‐ray diffraction measurements indicated some degree of Pt‐Sn alloying in the Pt‐Sn‐Eu/C catalysts, and mean crystallite sizes between 2.3–3.3 nm, while X‐ray photoelectron spectroscopy measurements showed the presence of Pt and Sn in both metallic and oxide form, and rare earth metals in the form of mixed oxides. Adding tin and europium promoted filling of the Pt 5d band, as confirmed by X‐ray absorption. The electrochemical characterization showed a higher oxidation current density and lower oxidation onset potential for the ternary Pt‐Sn‐Eu materials compared with the commercial catalysts, in both the three‐cell and fuel cell tests. High performance liquid chromatography measurements indicating that the main products of ethanol oxidation were acetaldehyde and acetic acid; a low concentration of CO2 was also detected. The improved ethanol oxidation efficiency for the Pt‐Sn‐Eu/C catalysts can be explained by the Sn/Eu‐Pt electronic effect, because it weakens the adsorption of intermediate products by Pt, and favors the bifunctional EOR mechanism, as europium oxide renders oxygenated species available at lower potentials.
Whole genome association study of brain‐wide imaging phenotypes: A study of the ping cohort
Authors: Wen Canhong , Mehta Chintan M. , Tan Haizhu , Zhang Heping
Published: February 2018

Neuropsychological disorders have a biological basis rooted in brain function, and neuroimaging data are expected to better illuminate the complex genetic basis of neuropsychological disorders. Because they are biological measures, neuroimaging data avoid biases arising from clinical diagnostic criteria that are subject to human understanding and interpretation. A challenge with analyzing neuroimaging data is their high dimensionality and complex spatial relationships. To tackle this challenge, we introduced a novel distance covariance tests that can assess the association between genetic markers and multivariate diffusion tensor imaging measurements, and analyzed a genome‐wide association study (GWAS) dataset collected by the Pediatric Imaging, Neurocognition, and Genetics (PING) study. We also considered existing approaches as comparisons. Our results showed that, after correcting for multiplicity, distance covariance tests of the multivariate phenotype yield significantly greater power at detecting genetic markers affecting brain structure than standard mass univariate GWAS of individual neuroimaging biomarkers. Our results underscore the usefulness of utilizing the distance covariance to incorporate neuroimaging data in GWAS.
Wnt signaling regulates proliferation and differentiation of radial glia in regenerative processes after stab injury in the optic tectum of adult zebrafish
Authors: Shimizu Yuki , Ueda Yuto , Ohshima Toshio
Published: February 2018

Zebrafish have superior abilities to generate new neurons in the adult brain and to regenerate brain tissue after brain injury compared with mammals. There exist two types of neural stem cells (NSCs): neuroepithelial‐like stem cells (NE) and radial glia (RG) in the optic tectum. We established an optic tectum stab injury model to analyze the function of NSCs in the regenerative condition and confirmed that the injury induced the proliferation of RG, but not NE and that the proliferated RG differentiated into new neurons after the injury. We then analyzed the involvement of Wnt signaling after the injury, using a Wnt reporter line in which canonical Wnt signaling activation induced GFP expression and confirmed that GFP expression was induced specifically in RG after the injury. We also analyzed the expression level of genes related to Wnt signaling, and confirmed that endogenous Wnt antagonist dkk1b expression was significantly decreased after the injury. We observed that Wnt signal inhibitor IWR1 treatment suppressed the proliferation and differentiation of RG after the injury, suggesting that up‐regulation of Wnt signaling in RG after the stab injury was required for optic tectum regeneration. We also confirmed that Wnt activation by treatment with GSK3β inhibitor BIO in uninjured zebrafish induced proliferation of RG in the optic tectum. This optic tectum stab injury model is useful for the study of the molecular mechanisms of brain regeneration and analysis of the RG functions in physiological and regenerative conditions.
Spatiotemporal integration of looming visual and tactile stimuli near the face
Authors: Huang Ruey‐Song , Chen Ching‐fu , Sereno Martin I.
Published: February 2018

Real‐world objects approaching or passing by an observer often generate visual, auditory, and tactile signals with different onsets and durations. Prompt detection and avoidance of an impending threat depend on precise binding of looming signals across modalities. Here we constructed a multisensory apparatus to study the spatiotemporal integration of looming visual and tactile stimuli near the face. In a psychophysical experiment, subjects assessed the subjective synchrony between a looming ball and an air puff delivered to the same side of the face with a varying temporal offset. Multisensory stimuli with similar onset times were perceived as completely out of sync and assessed with the lowest subjective synchrony index (SSI). Across subjects, the SSI peaked at an offset between 800 and 1,000 ms, where the multisensory stimuli were perceived as optimally in sync. In an fMRI experiment, tactile, visual, tactile‐visual out‐of‐sync (TVoS), and tactile‐visual in‐sync (TViS) stimuli were delivered to either side of the face in randomized events. Group‐average statistical responses to different stimuli were compared within each surface‐based region of interest (sROI) outlined on the cortical surface. Most sROIs showed a preference for contralateral stimuli and higher responses to multisensory than unisensory stimuli. In several bilateral sROIs, particularly the human MT+ complex and V6A, responses to spatially aligned multisensory stimuli (TVoS) were further enhanced when the stimuli were in‐sync (TViS), as expressed by TVoS < TViS. This study demonstrates the perceptual and neural mechanisms of multisensory integration near the face, which has potential applications in the development of multisensory entertainment systems and media.
Oscillatory dynamics in the dorsal and ventral attention networks during the reorienting of attention
Authors: Proskovec Amy L. , Heinrichs‐Graham Elizabeth , Wiesman Alex I. , McDermott Timothy J. , Wilson Tony W.
Published: February 2018

The ability to reorient attention within the visual field is central to daily functioning, and numerous fMRI studies have shown that the dorsal and ventral attention networks (DAN, VAN) are critical to such processes. However, despite the instantaneous nature of attentional shifts, the dynamics of oscillatory activity serving attentional reorientation remain poorly characterized. In this study, we utilized magnetoencephalography (MEG) and a Posner task to probe the dynamics of attentional reorienting in 29 healthy adults. MEG data were transformed into the time‐frequency domain and significant oscillatory responses were imaged using a beamformer. Voxel time series were then extracted from peak voxels in the functional beamformer images. These time series were used to quantify the dynamics of attentional reorienting, and to compute dynamic functional connectivity. Our results indicated strong increases in theta and decreases in alpha and beta activity across many nodes in the DAN and VAN. Interestingly, theta responses were generally stronger during trials that required attentional reorienting relative to those that did not, while alpha and beta oscillations were more dynamic, with many regions exhibiting significantly stronger responses during non‐reorienting trials initially, and the opposite pattern during later processing. Finally, stronger functional connectivity was found following target presentation (575‐700 ms) between bilateral superior parietal lobules during attentional reorienting. In sum, these data show that visual attention is served by multiple cortical regions within the DAN and VAN, and that attentional reorienting processes are often associated with spectrally‐specific oscillations that have largely distinct spatiotemporal dynamics.
Can climate variability information constrain a hydrological model for an ungauged Costa Rican catchment?
Authors: Quesada‐Montano Beatriz , Westerberg Ida K. , Fuentes‐Andino Diana , Hidalgo Hugo G. , Halldin Sven
Published: February 2018

Long‐term hydrological data are key to understanding catchment behaviour and for decision making within water management and planning. Given the lack of observed data in many regions worldwide, such as Central America, hydrological models are an alternative for reproducing historical streamflow series. Additional types of information—to locally observed discharge—can be used to constrain model parameter uncertainty for ungauged catchments. Given the strong influence that climatic large‐scale processes exert on streamflow variability in the Central American region, we explored the use of climate variability knowledge as process constraints to constrain the simulated discharge uncertainty for a Costa Rican catchment, assumed to be ungauged. To reduce model uncertainty, we first rejected parameter relationships that disagreed with our understanding of the system. Then, based on this reduced parameter space, we applied the climate‐based process constraints at long‐term, inter‐annual, and intra‐annual timescales. In the first step, we reduced the initial number of parameters by 52%, and then, we further reduced the number of parameters by 3% with the climate constraints. Finally, we compared the climate‐based constraints with a constraint based on global maps of low‐flow statistics. This latter constraint proved to be more restrictive than those based on climate variability (further reducing the number of parameters by 66% compared with 3%). Even so, the climate‐based constraints rejected inconsistent model simulations that were not rejected by the low‐flow statistics constraint. When taken all together, the constraints produced constrained simulation uncertainty bands, and the median simulated discharge followed the observed time series to a similar level as an optimized model. All the constraints were found useful in constraining model uncertainty for an—assumed to be—ungauged basin. This shows that our method is promising for modelling long‐term flow data for ungauged catchments on the Pacific side of Central America and that similar methods can be developed for ungauged basins in other regions where climate variability exerts a strong control on streamflow variability.
Targeting the multidrug transporter Patched potentiates chemotherapy efficiency on adrenocortical carcinoma in vitro and in vivo
Authors: Hasanovic Anida , Ruggiero Carmen , Jung Sara , Rapa Ida , Signetti Laurie , Ben Hadj Monia , Terzolo Massimo , Beuschlein Felix , Volante Marco , Hantel Constanze , Lalli Enzo , Mus‐Veteau Isabelle
Published: February 2018

One of the crucial challenges in the clinical management of cancer is the resistance to chemotherapeutics. We recently demonstrated that the Hedgehog receptor Patched, which is overexpressed in many recurrent and metastatic cancers, is a multidrug transporter for chemotherapeutic agents such as doxorubicin. The present work provides evidences that Patched is expressed in adrenocortical carcinoma (ACC) patients, and is a major player of the doxorubicin efflux and the doxorubicin resistance in the human ACC cell line H295R. We discovered that methiothepin inhibits the doxorubicin efflux activity of Patched. This drug‐like molecule enhances the cytotoxic, pro‐apoptotic, antiproliferative and anticlonogenic effects of doxorubicin on ACC cells which endogenously overexpress Patched, and thereby mitigates the resistance of these cancer cells to doxorubicin. Moreover, we report that in mice the combination of methiothepin with doxorubicin prevents the development of xenografted ACC tumors more efficiently than doxorubicin alone by enhancing the accumulation of doxorubicin specifically in tumors without obvious undesirable side effects. Our results suggest that the use of an inhibitor of Patched drug efflux such as methiothepin in combination with doxorubicin could be a promising therapeutic option for adrenocortical carcinoma, and most likely also for other Patched‐expressing cancers.
Spatio‐temporal map for early cancer detection: Proof of concept
Authors: Singh Pankaj , Sahoo Gyana Ranjan , Pradhan Asima
Published: February 2018

A spatio‐temporal map of human cervical tissue is obtained from time‐resolved fluorescence images with the dynamic contrast enhanced through principal component analysis (PCA) for clear demarcation of regions of normal and pre‐cancerous conditions. Changes in the properties of fluorescence in different environments are captured through fluorescence lifetime maps in the human cervical tissue sample. The correlation embodied in the second principal component (PC) representing sectorial information free of background of the first PC, segregates fluorescence activities, as illustrated in the PC maps. It significantly enhances the contrast of the images which are majorly handicapped by the variations in fluorophore environment. The result is validated on phantoms, mimicking the changes in the environment of normal and abnormal tissues. This spatio‐temporal map illustrates the potential of time resolved auto‐fluorescence imaging of cervical tissue in combination with PCA to clearly demarcate normal and abnormal regions with enhanced contrast.

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Gelatin–genipin‐based biomaterials for skeletal muscle tissue engineering
Authors: Gattazzo Francesca , De Maria Carmelo , Rimessi Alessandro , Donà Silvia , Braghetta Paola , Pinton Paolo , Vozzi Giovanni , Bonaldo Paolo
Published: February 2018

Skeletal muscle engineering aims at tissue reconstruction to replace muscle loss following traumatic injury or in congenital muscle defects. Skeletal muscle can be engineered by using biodegradable and biocompatible scaffolds that favor myogenic cell adhesion and subsequent tissue organization. In this study, we characterized scaffolds made of gelatin cross‐linked with genipin, a natural derived cross‐linking agent with low cytotoxicity and high biocompatibility, for tissue engineering of skeletal muscle. We generated gelatin–genipin hydrogels with a stiffness of 13 kPa to reproduce the mechanical properties characteristic of skeletal muscle and we show that their surface can be topographically patterned through soft lithography to drive myogenic cells differentiation and unidirectional orientation. Furthermore, we demonstrate that these biomaterials can be successfully implanted in vivo under dorsal mouse skin, showing good biocompatibility and slow biodegradation rate. Moreover, the grafting of this biomaterial in partially ablated tibialis anterior muscle does not impair muscle regeneration, supporting future applications of gelatin–genipin biomaterials in the field of skeletal muscle tissue repair. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2763–2777, 2018.
Proof‐of‐concept study of vertical augmentation using block‐type allogenic bone grafts: A preclinical experimental study on rabbit calvaria
Authors: Lee Ji‐Sun , Lee Jung‐Seok , Kang Myung‐Hun , Jung Ui‐Won , Choi Seong‐Ho , Cho Kyoo‐Sung
Published: February 2018

This study aimed to quantify the healing following vertical augmentation of allogenic bone blocks with/without recombinant human bone morphogenetic protein‐2 (rhBMP‐2) on rabbit calvaria. Experiments were performed using allogenic bone blocks which were grafted bilaterally with or without rhBMP‐2 on 20 rabbit calvaria, and these animals were divided to four groups according to the use of rhBMP‐2 and healing periods (2 and 8 weeks; n = 10 in each group). Onlay‐type bone blocks (8 mm in diameter and 5 mm high) were fixed with a self‐tapping screw after removing the cortex in the control group, and the same protocol was applied with the addition of soaking the bone blocks with rhBMP‐2 for 15 min in the test group. Radiographic and histologic analyses were performed after 2 or 8 weeks to evaluate the volumetric stability and bone regeneration within the grafted area. The radiographic analysis revealed that the height of the allogenic bone block decreased but its volume was maintained from 2 to 8 weeks in both the control and test groups. The histologic results demonstrated a statistically significant increase in new bone area in the test group, especially in the lower region adjacent to the preexisting calvarial floor. The amount of newly formed bone in all regions of the augmented bone blocks in both the control and test groups was greater at 8 weeks than at 2 weeks. In conclusion, the vertically grafted allogenic bone block maintained its volume with new bone formation, and this was accelerated by the addition of rhBMP‐2. These findings indicate that allogenic bone block soaked with rhBMP‐2 could be a useful candidate biomaterial for vertical augmentation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2700–2707, 2018.
Optimizing Sequential and Combined Anabolic and Antiresorptive Osteoporosis Therapy
Authors: Leder Benjamin Z
Published: February 2018

As osteoporosis therapy options have expanded, and clinical guidelines have begun to embrace the concept of limited treatment courses and “drug holidays,” the choices that physicians must make when initiating, electing to continue, or switching therapies have become more complex. As a result, one of the fundamental issues that must be carefully considered is whether, when, and in what sequence anabolic therapies should be utilized. This review evaluates the current evidence supporting the optimal sequence for the use of anabolic and antiresorptive drugs and assesses the expanding number of clinical trials favoring the initial use of anabolic therapy followed by an antiresorptive agent. This review also explores the evidence suggesting that the effectiveness of anabolic medications are diminished when used in patients that have been previously treated with specific antiresorptive drugs for prolonged periods. Finally, the recent advances in designing combination antiresorptive/anabolic treatment approaches are detailed, with a focus on combined denosumab/teriparatide regimens, which appear to provide the most substantial and clinically relevant skeletal benefits to patients with established osteoporosis. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Cover Image, Volume 93, Issue 3
Authors: Chen Qi , Yu Zongxue , Li Fei , Yang Yang , Pan Yang , Peng Yixin , Yang Xi , Zeng Guangyong
Published: February 2018

The cover image, by Qi Chen et al., is based on the Research Article A novel photocatalytic membrane decorated with RGO‐Ag‐TiO2 for dye degradation and oil‐water emulsion separation, DOI: 10.1002/jctb.5426.

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Optimization of on‐site cellulase preparation for efficient hydrolysis of atmospheric glycerol organosolv pretreated wheat straw
Authors: Sun Fubao , Mukasekuru Marie Rose , Tan Ling , Ren Junli , Huang Zhenxing , Ren Hongyan , Zhang Zhanying
Published: February 2018

BACKGROUND

The cost of using cellulase to effectively release fermentable sugars from lignocellulosic substrates is still a major impediment to development of the enzyme‐based ‘biorefinery’ industry. This study attempted to optimize a cellulase preparation from on‐site fermentation to efficiently hydrolyse atmospheric glycerol organosolv (AGO)‐pretreated wheat straw.

RESULTS

Addition of Cu2+, PEG10000, L‐ascorbic acid and trehalose in the fermentation medium significantly improved the cellulase production. Use of all the additives enabled enhancement to 45.5% of filter paper cellulase (FPA), 14.7% of β‐glucosidase (BG) and 32.4% of carboxymethyl cellulase (CMCase). With the on‐site production of crude cellulase, accessory enzymes (β‐glucosidase (BG), xylanase and lysozyme) and additives (tea saponin (TS) and cationic polyacrylamide (c‐PAM)) were found to facilitate the hydrolysis of AGO‐pretreated substrates effectively. The optimized cellulase mixture allowed 96% of enzymatic hydrolysis at 5 FPU g‐1 for 48 h on addition of 11.5 U g‐1 BG, 180 U g‐1 xylanase, 45 U g‐1 lysozyme, 10 mg g‐1 TS and 2 mg g‐1 C‐PAM, which was twice that of the crude cellulase broth.

CONCLUSION

Cellulase customization for specific substrate hydrolysis with on‐site produced broth produced an efficient pathway to lower the enzyme cost in the ongoing lignocellulosic biorefining industry. © 2018 Society of Chemical Industry
Synthesis and Bioactivity of Quinoline‐3‐carboxamide Derivatives
Authors: Govender Hogantharanni , Mocktar Chunderika , Koorbanally Neil A.
Published: February 2018

Twelve novel substituted 2‐chloroquinoline‐3‐carboxamide derivatives were prepared from acetanilides using the Vilsmeier–Haack reaction, producing 2‐chloro‐3‐carbaldehyde quinolines, followed by oxidation of the 3‐carbaldehyde to the carboxylic acid and coupling this group with various anilines. The structures of the synthesized compounds were confirmed by NMR, mass spectrometry, and single crystal X‐ray diffraction. The chemical shifts of H‐5 and H‐8 were shown to be influenced by the substituent at C‐6. The substituent at C‐6 was also seen to affect the chemical shift of C‐5, C‐7, and C‐8, with C‐5 and C‐7 being more shielded in 5j (F substituted) in comparison with 5g (Cl substituted) and 5d (CH3 substituted). The compounds showed weak activity in the mM range against Gram‐positive and Gram‐negative bacteria of which 5b, 5d, and 5f showed the best activity with minimum bactericidal concentration values for 5b being 3.79 mM against methicillin‐resistant Staphylococcus aureus and 5d and 5f having minimum bactericidal concentration values of 3.77 and 1.79 mM against S. aureus ATCC 25923, respectively.
Histogram analysis of stretched‐exponential and monoexponential diffusion‐weighted imaging models for distinguishing low and intermediate/high gleason scores in prostate carcinoma
Authors: Liu Wei , Liu Xiao H. , Tang Wei , Gao Hong B. , Zhou Bing N. , Zhou Liang P.
Published: February 2018

Background

Noninvasive measures to evaluate the aggressiveness of prostate carcinoma (PCa) may benefit patients.

Purpose

To assess the value of stretched‐exponential and monoexponential diffusion‐weighted imaging (DWI) for predicting the aggressiveness of PCa.

Study Type

Retrospective study.

Subjects

Seventy‐five patients with PCa.

Field Strength

3T DWI examinations were performed using b‐values of 0, 500, 1000, and 2000 s/mm2.

Assessment

The research were based on entire‐tumor histogram analysis and the reference standard was radical prostectomy.

Statistical Tests

The correlation analysis was programmed with Spearman's rank‐order analysis between the histogram variables and Gleason grade group (GG). Receiver operating characteristic (ROC) regression was used to analyze the ability of these histogram variables to differentiate low‐grade (LG) from intermediate/high‐grade (HG) PCa.

Results

The percentiles and mean of apparent diffusion coefficient (ADC) and distributed diffusion coefficient (DDC) were correlated with GG (ρ: 0.414–0.593), while there was no significant relation among α value, skewnesses, and kurtosises with GG (ρ:0.034–0.323). HG tumors (ADC:484 ± 136, 592 ± 139, 670 ± 144, 788 ± 146, 895 ± 141 mm2/s; DDC: 410 ± 142, 532 ± 172, 666 ± 193, 786 ± 196, 914 ± 181 mm2/s) had lower values in the 10th, 25th, 50th, 75th percentiles and means than LG tumors (ADC: 644 ± 779, 737 ± 84, 836 ± 83, 919 ± 82, 997 ± 107 mm2/s; DDC: 552 ± 82, 680 ± 94, 829 ± 112, 931 ± 106, 1045 ± 100 mm2/s). However, there was no difference between LG and HG tumors in α value (0.671 ± 0.041 vs. 0.633 ± 0.114), kurtosises (ADC 0.09 vs. 0.086; DDC –0.033 vs. –0.317), or skewnesses (ADC –0.036 vs. 0.073; DDC –0.063 vs. 0.136). The above statistics were P < 0.01. ADC10 with AUC = 0.840 and DDC10 with AUC = 0.799 were similar in discriminating between LG and HG PCa at P < 0.05.

Data Conclusion

Histogram variables of DDC and ADC may predict the aggressiveness of PCa, while α value does not. The abilities of ADC10 and DDC10 to discriminate LG from HG tumors were similar, and both better than their respective means.

Level of Evidence: 3

Technical Efficacy: Stage 1

J. MAGN. RESON. IMAGING 2018;48:491–498.
Silver‐109‐based laser desorption/ionization mass spectrometry method for detection and quantification of amino acids
Authors: Arendowski Adrian , Nizioł Joanna , Ruman Tomasz
Published: February 2018

A new methodology applicable for both high‐resolution laser desorption/ionization mass spectrometry and mass spectrometry imaging of amino acids is presented. The matrix‐assisted laser desorption ionization‐type target containing monoisotopic cationic 109Ag nanoparticles (109AgNPs) was used for rapid mass spectrometry measurements of 11 amino acids of different chemical properties. Amino acids were directly tested in 100,000‐fold concentration change conditions ranging from 100 μg/mL to 1 ng/mL which equates to 50 ng to 500 fg of amino acid per measurement spot. Limit of detection values obtained suggest that presented method/target system is among the fastest and most sensitive ones in laser mass spectrometry. Mass spectrometry imaging of spots of human blood plasma spiked with amino acids showed their surface distribution allowing optimization of quantitative measurements.
Surface‐enhanced micro‐CARS mapping of a nanostructured cerium dioxide/aluminum film surface with gold nanoparticle‐bound organic molecules
Authors: Fabelinsky Viktor I. , Kozlov Dimitrii N. , Orlov Sergey N. , Polivanov Yury N. , Shcherbakov Ivan A. , Smirnov Valery V. , Vereschagin Konstantin A. , Arzumanyan Grigory M. , Mamatkulov Kahramon Z. , Afanasiev Konstantin N. , Lagarkov Andrey N. , Ryzhikov Ilya A. , Sarychev Andrey K. , Budashov Igor A. , Nechaeva Natalia L. , Kurochkin Ilya N.
Published: February 2018

Highly contrast epi‐surface‐enhanced coherent anti‐Stokes Raman scattering (SECARS) microimages of Au‐nanoparticle‐bound organic reporter molecule distributions at a surface of novel surface‐enhanced Raman scattering (SERS)‐active metamaterial junctions, based on nanoparticles spread over a nanostructured CeO2 faceted dielectric film, deposited on an Al sublayer, were recorded at two‐color picosecond excitation of the surface in the near‐infrared spectral range. For this, a scanning confocal laser‐based micro‐CARS spectrometer was employed. The investigations showed that at Raman resonant laser excitation of the molecules/Au‐NP conjugates immobilized on the surface strong SECARS signals can be generated with laser powers not deteriorating the conjugates. Coupling CARS with the plasmonic metamaterial structures under investigation provided excellent chemical imaging contrast (up to 400) for biochemically relevant 5‐thio(2‐nitrobenzoic acid) and 4‐mercaptophenylboronic acid reporter molecules. Taking into account easy handling and utmost long‐term stability of the investigated metamaterial junction at ambient conditions, it might be considered as a promising perspective for a single‐molecule‐sensitivity surface‐enhanced Raman scattering or SECARS biosensor.
Current methods for mycotoxins analysis and innovative strategies for their reduction in cereals: an overview
Authors: Shanakhat Hina , Sorrentino Angela , Raiola Assunta , Romano Annalisa , Masi Paolo , Cavella Silvana
Published: February 2018

Mycotoxins are secondary metabolites produced by moulds in food that are considered a substantial issue in the context of food safety, due to their acute and chronic toxic effects on animals and humans. Therefore, new accurate methods for their identification and quantification are constantly developed in order to increase the performance of extraction, improve the accuracy of identification and reduce the limit of detection. At the same time, several industrial practices have shown the ability to reduce the level of mycotoxin contamination in food. In particular, a decrease in the amount of mycotoxins could result from standard processes naturally used for food processing or by procedures strategically introduced during processing, with the specific aim of reducing the amount of mycotoxins. In this review, the current methods adopted for accurate analyses of mycotoxins in cereals (aflatoxins, ochratoxins, trichothecenes, fumonisins) are discussed. In addition, both conventional and innovative strategies adopted to obtain safer finished products from common cereals intended for human consumption will be explored and analysed. © 2018 Society of Chemical Industry