bluuebunny/crossref_metadata_2025 huggingface dataset:
Microparticles Locally Deliver Active Interleukin‐1 Receptor Antagonist In Vivo
Authors: Clements Anna E. B. , Groves Emily R. , Chamberlain Connie S. , Vanderby Ray , Murphy William L.
Published: July 2018

Despite significant research in therapeutic protein delivery, localized and sustained delivery of active therapeutic proteins remains a challenge. Delivery is a particular challenge for therapeutic proteins with a short half‐life. Herein, localized delivery of interleukin‐1 receptor antagonist (IL‐1Ra) by mineral coated microparticles (MPs) is assessed in a healing rat medial collateral ligament (MCL). The local tissue concentration and systemic serum concentration of IL‐1Ra, the anti‐inflammatory activity of IL‐1Ra delivered with MPs, and whether IL‐1Ra loaded MPs (IL‐1Ra MPs) are immunogenic in a healing ligament are also examined. IL‐1Ra MPs significantly increase the local concentration of IL‐1Ra compared to soluble IL‐1Ra at 7 and 14 days after treatment but do not elevate the systemic concentration of IL‐1Ra at these time points, indicating localized delivery of IL‐1Ra. IL‐1Ra MPs significantly reduce inflammation caused by the MPs themselves, indicating the IL‐1Ra is active. Finally, IL‐1Ra MPs do not induce a foreign body response and decrease the immunogenicity of human IL‐1Ra in a healing rat MCL. Overall, mineral coated microparticles have the ability to locally deliver active therapeutic proteins for an extended period of time.
Progress in Applications of Prussian Blue Nanoparticles in Biomedicine
Authors: Qin Zhiguo , Li Yan , Gu Ning
Published: July 2018

Prussian blue nanoparticles (PBNPs) with favorable biocompatibility and unique properties have captured the attention of extensive biomedical researchers. A great progress is made in the application of PBNPs as therapy and diagnostics agents in biomedicine. This review begins with the recent synthetic strategies of PBNPs and the regulatory approaches for their size, shape, and uniformity. Then, according to the different properties of PBNPs, their application in biomedicine is summarized in detail. With modifiable features, PBNPs can be used as drug carriers to improve the therapeutic efficacy. Moreover, the exchangeable protons and adsorbability enable PBNPs to decontaminate the radioactive ions from the body. For biomedical imaging, photoacoustic and magnetic resonance imaging based on PBNPs are summarized, as well as the strategies to improve the diagnostic effectiveness. The applications related to the photothermal effects and nanoenzyme activities of PBNPs are described. The challenges and critical factors for the clinical translation of PBNPs as multifunctional theranostic agents are also discussed. Finally, the future prospects for the application of PBNPs are considered. The aim of this review is to provide a better understanding and key consideration for rational design of this increasingly important new paradigm of PBNPs as theranostics.
Controlling Nerve Growth with an Electric Field Induced Indirectly in Transparent Conductive Substrate Materials
Authors: Rajnicek Ann M. , Zhao Zhiqiang , Moral‐Vico Javier , Cruz Ana M. , McCaig Colin D. , Casañ‐Pastor Nieves
Published: July 2018

Innovative neurostimulation therapies require improved electrode materials, such as poly(3,4‐ethylenedioxythiophene) (PEDOT) polymers or IrOx mixed ionic–electronic conductors and better understanding of how their electrochemistry influences nerve growth. Amphibian neurons growing on transparent films of electronic (metal) conductors and electronic–ionic conductors (polymers and semiconducting oxides) are monitored. Materials are not connected directly to the power supply, but a dipole is created wirelessly within them by electrodes connected to the culture medium in which they are immersed. Without electrical stimulation neurons grow on gold, platinum, PEDOT‐polystyrene sulfonate (PEDOT‐PSS), IrOx, and mixed oxide (Ir‐Ti)Ox, but growth is not related to surface texture or hydrophilicity. Stimulation induces a dipole in all conductive materials, but neurons grow differently on electronic conductors and mixed‐valence mixed‐ionic conductors. Stimulation slows, but steers neurite extension on gold but not on platinum. The rate and direction of neurite growth on PEDOT‐PSS resemble that on glass, but on IrOx and (Ir‐Ti)Ox neurites grow faster and in random directions. This suggests electrochemical changes induced in these materials control growth speed and direction selectively. Evidence that the electric dipole induced in conductive material controls nerve growth will impact electrotherapies exploiting wireless stimulation of implanted material arrays, even where transparency is required.
Effect of Ar, O2, and N2 Plasma on the Growth and Composition of Vanadium Oxide Nanostructured Thin Films
Authors: Singh Megha , Kumar Prabhat , Reddy Gade Brahmaiah
Published: July 2018

Vanadium oxide nanostructured thin films (NTFs) are synthesized using plasma assisted sublimation process (PASP) in different gases' Ar, O2, and N2 plasma (AP, OP, and NP) and O2 gas (OG) ambient. Morphological studies conducted via electron microscopy reveal nanostrips, nanoflakes, nanorods, and nanoparticles organized as clusters for OP, OG, AP, and NP respectively. X‐ray photoelectron spectroscopy (XPS) studies show that samples OP and OG are composed of α‐V2O5, whereas AP and NP are composed of V6O13 along with V2O5. The relative percentages calculated using XPS data show that in AP, V6O13, and V2O5 are 38 and 62%, respectively. These percentages change to 48% for V6O13 and 52% for V2O5 in NP. The V6O13/V2O5 ratio is lower in AP than NP. This increment of V6O13 in NP is due to presence of more reductive species in N2 plasma than Ar plasma. Since N2 plasma contains species like N*, , etc. it leads to the formation of NO2, N2O, etc. Raman spectra indicate the surface of the sample NP consisting of both V6O13 and V2O5, agreeing with the X‐ray diffraction (XRD) and XPS results. Studies demonstrate that plasma ambient during synthesis process affects both morphology and composition of deposited vanadium oxide NTFs.
Merging Electric Bacteria with Paper
Authors: Gao Yang , Choi Seokheun
Published: July 2018

Paper‐based electronics (papertronics) are recently considered as one of the most exciting device platforms because of their flexibility, sustainability, eco‐friendliness, and low cost as well as their excellent mechanical, dielectrical, and fluidic properties. Now, innovative structure engineering techniques can manipulate diameters of the cellulose fibers of paper, smoothing the roughness and controlling the transparency for numerous device applications. Novel functionalization techniques of paper with organic, inorganic, and biological entities enable many engineering possibilities, revolutionizing papertronics for the next generation of electronics. Among those techniques for new functionalities, integrating electric bacteria into paper has attracted considerable interest as a new energy technique for papertronics. Paper has unique synergistic characteristics including a porous and hydrophilic environment for bacterial viability, a high surface area for bacterial accumulation, and sustainability even in resource‐limited settings. In this work, comprehensive analytical and experimental approaches to provide a novel but realistic and accessible power source from bacteria loaded into paper are pursued. This report provides new approaches to revolutionarily activate the biobattery and significantly improve its shelf life. Furthermore, for the first time the practical efficacy of the explored technique is ensured, generating on‐demand energy even in resource‐limited environments.
Doped Nanocarbons Derived from Conducting Polymers toward ORR Electrocatalysts
Authors: Li Yanan , Liu Yingwei , Fan Lei , Yuan Ganyin , Han Jie , Guo Rong
Published: July 2018

Developing nonprecious electrocatalysts for efficient oxygen reduction reactions (ORR) has aroused increasing interest recently. Doped nanocarbons derived from conducting polymers have emerged as a competitive class of nonprecious‐metal catalysts for the ORR because of their promising catalytic activities, long‐standing stability, and particularly low‐cost and facile preparation at a large scale via simple approaches. This review summarizes the recent progress of the preparation and application as ORR electrocatalysts of heteroatom doped nanocarbons derived from conducting polymers, and transition metal and heteroatom‐codoped nanocarbons from conducting polymers and metal salts. Finally, the challenges and further development of this field are also discussed.
Optimized Salt Selection for Solar Thermal Latent Heat Energy Storage
Authors: Raud Ralf , Bell Stuart , Ong Teng‐Cheong , Will Geoffrey , Steinberg Theodore A.
Published: July 2018

For solar thermal power to be cost effective as a baseload generation paradigm, the cost and efficiency of every subsystem must be improved. To reduce the cost of thermal storage and increase the working temperature of the subsystems for greater efficiency, appropriate storage materials must be identified for study. Unfortunately, there is an enormous search space of salt mixtures that are suitable candidates for thermal storage and must be analyzed for cost effectiveness to determine which candidates are the best. To lessen the experimental burden, this article combines previously validated theories for estimating the properties of salt mixtures with an analytic design optimization method to better estimate the true cost of each candidate. Five hundred and sixty three binary, ternary, and quaternary mixtures are analyzed. Five mixtures are identified as the prime candidates for a cascaded latent heat thermal energy storage system for a supercritical CO2 Brayton cycle generator. This system is cheaper than the Sunshot Initiative cost targets, bringing the solar thermal paradigm into cost competition with fossil fuels.
Subthreshold Operation of Organic Electrochemical Transistors for Biosignal Amplification
Authors: Venkatraman Vishak , Friedlein Jacob T. , Giovannitti Alexander , Maria Iuliana P. , McCulloch Iain , McLeod Robert R. , Rivnay Jonathan
Published: July 2018

With a host of new materials being investigated as active layers in organic electrochemical transistors (OECTs), several advantageous characteristics can be utilized to improve transduction and circuit level performance for biosensing applications. Here, the subthreshold region of operation of one recently reported high performing OECT material, poly(2‐(3,3′‐bis(2‐(2‐(2‐methoxyethoxy)ethoxy)ethoxy)‐[2,2′‐bithiophen]‐5‐yl)thieno[3,2‐b]thiophene), p(g2T‐TT) is investigated. The material's high subthreshold slope (SS) is exploited for high voltage gain and low power consumption. An ≈5× improvement in voltage gain (AV) for devices engineered for equal output current and 370× lower power consumption in the subthreshold region, in comparison to operation in the higher transconductance (g m), superthreshold region usually reported in the literature, are reported. Electrophysiological sensing is demonstrated using the subthreshold regime of p(g2T‐TT) devices and it is suggested that operation in this regime enables low power, enhanced sensing for a broad range of bioelectronic applications. Finally, the accessibility of the subthreshold regime of p(g2T‐TT) is evaluated in comparison with the prototypical poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), and the role of material design in achieving favorable properties for subthreshold operation is discussed.
Cancer evolution and heterogeneity
Authors: Mimori Koshi , Saito Tomoko , Niida Atsushi , Miyano Satoru
Published: July 2018

Undoubtedly, intratumor heterogeneity (ITH) is one of the causes of the intractability of cancers. Recently, technological innovation in genomics has promoted studies on ITH in solid tumors and on the pattern and level of diversity, which varies among malignancies. We profiled the genome in multiple regions of nine colorectal cancer (CRC) cases. The most impressive finding was that in the late phase, a parental clone branched into numerous subclones. We found that minor mutations were dominant in advanced CRC named neutral evolution; that is, driver gene aberrations were observed with high proportion in the early‐acquired phase, but low in the late‐acquired phase. Then, we validated that neutral evolution could cause ITH in advanced CRC by super‐computational analysis. According to the clinical findings, we explored a branching evolutionary process model in cancer evolution, which assumes that each tumor cell has cellular automaton. According to the model, we verified factors to foster ITH with neutral evolution in advanced CRC. In this review, we introduce recent advances in the field of ITH including the general component of ITH, clonal selective factors that consolidate the evolutionary process, and a representative clinical application of ITH.
Aspects of Frequentism
Authors: Caldwell Allen
Published: July 2018

Some aspects of the Frequentist approach to statistical data analysis are presented and discussed. The construction of confidence intervals for parameters is explained and made concrete with a detailed example. The intervals correspond to parameter ranges where the observed data is in a ‘favored’ part of the expected results distribution. Goodness‐of‐fit tests are defined similarly; here, a Bayesian argument is given for the usefulness of these tests. The possible over‐interpretation of Frequentist results is also discussed.
Control over Electrochemical Water Oxidation Catalysis by Preorganization of Molecular Ruthenium Catalysts in Self‐Assembled Nanospheres
Authors: Yu Fengshou , Poole David , Mathew Simon , Yan Ning , Hessels Joeri , Orth Nicole , Ivanović‐Burmazović Ivana , Reek Joost N. H.
Published: July 2018

Oxygen formation through water oxidation catalysis is a key reaction in the context of fuel generation from renewable energies. The number of homogeneous catalysts that catalyze water oxidation at high rate with low overpotential is limited. Ruthenium complexes can be particularly active, especially if they facilitate a dinuclear pathway for oxygen bond formation step. A supramolecular encapsulation strategy is reported that involves preorganization of dilute solutions (10−5 m) of ruthenium complexes to yield high local catalyst concentrations (up to 0.54 m). The preorganization strategy enhances the water oxidation rate by two‐orders of magnitude to 125 s−1, as it facilitates the diffusion‐controlled rate‐limiting dinuclear coupling step. Moreover, it modulates reaction rates, enabling comprehensive elucidation of electrocatalytic reaction mechanisms.
Microbiota‐Dependent Involvement of Th17 Cells in Murine Models of Inflammatory Arthritis
Authors: Evans‐Marin Heather , Rogier Rebecca , Koralov Sergei B. , Manasson Julia , Roeleveld Debbie , van der Kraan Peter M. , Scher Jose U. , Koenders Marije I. , Abdollahi‐Roodsaz Shahla
Published: July 2018

Objective

Intestinal microbiota are associated with the development of inflammatory arthritis. The aim of this study was to dissect intestinal mucosal immune responses in the preclinical phase of arthritis and determine whether the presence of Th17 cells, beyond involvement of the cytokine interleukin‐17 (IL‐17), is required for arthritis development, and whether the involvement of Th17 cells in arthritis depends on the composition of the host microbiota.

Methods

Mucosal T cell production of IL‐17, interferon‐γ, tumor necrosis factor α (TNFα), IL‐22, and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) was analyzed by flow cytometry and Luminex assay before arthritis onset in mice immunized to develop collagen‐induced arthritis (CIA). Pathogenic features of arthritis in mice with CIA and mice with antigen‐induced arthritis were compared between Th17 cell–deficient (CD4‐Cre+Rorcflox/flox) and Th17 cell–sufficient (CD4‐Cre−Rorcflox/flox) mice. In addition, the impact of intestinal microbiota on the Th17 cell dependence of CIA was assessed.

Results

Lamina propria CD4 T cells were activated before the onset of arthritis in mice with CIA, with marked up‐regulation of several cytokines, including IL‐17A, TNFα, and GM‐CSF. CD4‐Cre+Rorcflox/flox mice showed a specific reduction in intestinal mucosal levels of Th17 cells and partially reduced levels of IL‐17–producing CD8 T cells. However, total levels of IL‐17A, mostly produced by γδ T cells and neutrophils, were unaffected. The severity of arthritis was significantly reduced in Th17 cell–deficient mice, suggesting that Th17 cells have additional, IL‐17A–independent roles in inflammatory arthritis. Accordingly, antigen‐stimulated T cells from Th17 cell–deficient mice produced less IL‐17A, IL‐17F, and GM‐CSF. Importantly, the dependence of CIA on the involvement of Th17 cells was mitigated in the presence of an alternative microbiome.

Conclusion

These data from murine models suggest that activation of mucosal immunity precedes the development of arthritis, and also that Th17 cells have a microbiota‐dependent role in arthritis. Therefore, a microbiome‐guided stratification of patients might improve the efficacy of Th17‐targeted therapies.
Frankenstein or a Submarine Alkaline Vent: Who is Responsible for Abiogenesis?
Authors: Branscomb Elbert , Russell Michael J.
Published: July 2018

We argued in Part 1 of this series that because all living systems are extremely far‐from‐equilibrium dynamic confections of matter, they must necessarily be driven to that state by the conversion of chemically specific external disequilibria into specific internal disequilibria. Such conversions require task‐specific macromolecular engines. We here argue that the same is not only true of life at its emergence; it is the enabling cause of that emergence; although here the external driving disequilibria, and the conversion engines needed must have been abiotic. We argue further that the initial step in life's emergence can only create an extremely simple non‐equilibrium “seed” from which all the complexity of life must then develop. We assert that this complexity develops incrementally and progressively, each step tested for value added “in flight.” And we make the case that only the submarine alkaline hydrothermal vent (AHV) model has the potential to satisfy these requirements.
The Synergistic Effect of CuZnCeOx in Controlling the Formation of Methanol and CO from CO2 Hydrogenation
Authors: Hu Xiaosong , Qin Wei , Guan Qingxin , Li Wei
Published: July 2018

CO2 hydrogenation will be essential for a sustainable society if methanol and CO can be efficiently obtained using appropriate catalysts. In this paper, a highly efficient CuZnCeOx catalyst was synthesized using a parallel flow coprecipitation method, and was evaluated in CO2 hydrogenation to produce methanol and CO. Interestingly, the catalyst shows excellent activity and stability, and the selectivity of the products can be controlled by the amount of CeOx. Characterization results show that a significant synergistic effect between Cu and metal oxides (ZnO and/or CeOx) was observed at the composite catalysts. Cu plays a critical role in the activation of H2, and CeOx strongly adsorbs CO2. CeOx improved the dispersion of Cu nanoparticles and promoted the spillover of atomic hydrogen, which was beneficial to the generation of methanol. Meanwhile, ZnO exhibited weak adsorption ability for CO2, which was beneficial for the generation of CO. In addition, ZnO can significantly improve the dispersion of the CeOx nanoparticles. Both the dispersion of active sites and the activation abilities of CO2 are critical for catalyst activity and product selectivity. Thus, the ternary catalyst CuZnCeOx shows higher performance than the binary catalysts (CuZnOx and CuCeOx) in the CO2 hydrogenation reaction. This paper provides a viable way to produce selectively methanol or CO from CO2 hydrogenation.
HPV RNA in situ hybridization can inform cervical cytology‐histology correlation
Authors: Coppock Joseph D. , Willis Brian C. , Stoler Mark H. , Mills Anne M.
Published: July 2018

BACKGROUND

In situ hybridization for human papillomavirus (HPV) messenger RNA (HPV RNA ISH) recently was introduced as an ancillary tool in the diagnosis of cervical squamous intraepithelial lesions, and can aid in the distinction between low‐grade squamous intraepithelial lesions (LSILs) versus reactive/negative biopsies. Prior work has shown that up to one‐half of cases originally diagnosed as LSIL are reclassified as negative/reactive by expert consensus review of morphology, and negative HPV RNA ISH results most often correlate with an expert diagnosis of negative/reactive. Given that LSIL overdiagnoses on biopsy may result in the erroneous clinical impression that a cervical lesion has been sampled appropriately, the authors proposed that HPV RNA ISH can inform cytology‐histology correlation for challenging LSIL biopsies.

METHODS

A total of 92 cervical biopsies originally diagnosed as LSIL were reviewed by 3 gynecologic pathologists and reclassified based on consensus opinion of morphology. ISH was performed for high‐risk and low‐risk HPV E6/E7 mRNA. Prior/concurrent cytology results were collected.

RESULTS

Based on expert consensus morphologic review, 49% of biopsies (45 of 92 biopsies) originally diagnosed as LSIL were reclassified as negative, 6.5% (6 of 92 biopsies) were reclassified as high‐grade squamous intraepithelial lesion, and 44.5% (41 of 92 biopsies) were maintained as LSIL. The majority of LSIL biopsies reclassified as negative (80%; 36 of 45 biopsies) were HPV RNA negative, whereas 93% of LSIL biopsies (39 of 41 biopsies) and 100% of high‐grade squamous intraepithelial lesion biopsies were HPV RNA positive.

CONCLUSIONS

LSIL often is overdiagnosed by morphology on biopsy, potentially leading to the false impression that a lesion identified on cytology has been sampled. Performing RNA ISH on biopsies decreases histologic LSIL overdiagnosis, and potentially can prompt further sampling when there is cytology‐histology discordance. Cancer (Cancer Cytopathol) 2018. © 2018 American Cancer Society.
Design of NS3 VLC module and performance analysis of ad hoc network under VLC and Wi‐Fi layers
Authors: Sheikh Saad M. , Ali Hamza R. , Asif Hafiz M. , Baig Sobia , Khan Asim A.
Published: July 2018

Visible light communication (VLC) is the branch of optical wireless communications that uses light‐emitting diodes for the dual purpose of illumination and very‐high‐speed data communication. The main motivation behind the current work is finding alternatives to the saturated radio frequency spectrum, radio frequency security issue, and vulnerability to interferences. The current work is aimed at developing a module for the physical layer of a VLC‐based ad hoc network in network simulation 3. The VLC physical layer module is developed by using the optical signal modules available in the network simulator. The work also includes modelling of VLC‐based transmitter, wireless optical channel, and the optical receiver. Furthermore, the implementation and evaluation of the VLC‐based physical layer is carried out over a typical ad hoc network under different performance metrics. The designed ad hoc network is also tested under Wi‐Fi module followed by its comparison with corresponding ad hoc network under VLC module. The comparison is based on bit error rate curves, system throughput, and gain in received signal‐to‐noise ratio mainly. Finally, the suitability of different modulation schemes is also investigated in the current work for both Wi‐Fi– and VLC‐based ad hoc networks.
DTR‐mediated conditional cell ablation—Progress and challenges
Authors: Ruedl Christiane , Jung Steffen
Published: July 2018

Cell ablation is a valuable complement to mutagenesis for experimentally defining specific cell functions in physiology and pathophysiology in small animal models. One of the most popular ablation strategies involves transgenic expression of a primate diphtheria toxin receptor (DTR) on murine cells that are otherwise resistant to the bacterial exotoxin. The efforts of many laboratories using the DTR approach over the years have yielded numerous valuable insights into specific cell functions. Here, we will discuss the technical aspects of the DTR approach, including the strengths, pitfalls, and future strategies to overcome the shortcomings, highlighting a recent paper published in the European Journal of Immunology [El Hachem et al. Eur. J. Immunol. 2018 https://doi.org/10.1002/eji.201747351]. A particular focus will be given to the application of DTR approach to decipher in vivo functions of the murine myeloid cell compartment.
Multifunctional Photostable Nanocomplex of ZnO Quantum Dots and Avobenzone via the Promotion of Enolate Tautomer
Authors: Asok Adersh , Deshlahra Prashant , Ramachandran Animesh M. , Kulkarni Ajit R.
Published: July 2018

Ideal multifunctional ultraviolet radiation (UVR) absorbents with excellent photostability, high molar absorptivity, broadband UVR screening, and desired skin sensorial properties remain a significant challenge for the sunscreen industry. The potential of the nanocomplex (NCx) formed by microwave synthesis of ZnO quantum dots (QDs) in the presence of Avobenzone (Av) for achieving these goals is reported. The NCx exhibits unique synergy between ZnO QD and Av components, which enhances the photostability and molar absorptivity, extends UVA filtering range, and provides a visible emission that matches the typical human in vivo skin emission color. Density functional theory (DFT) and time‐dependent DFT calculations of ZnO‐Av hybrid structures and comparison of their spectroscopic features with experiments suggest that ZnO QDs catalyze the formation of highly photostable surface enolate species via aldol condensation reaction. The combination of experiments and computations used in this study can advance the science and technology of photoprotection.
The fronto‐insular cortex causally mediates the default‐mode and central‐executive networks to contribute to individual cognitive performance in healthy elderly
Authors: Li Rui , Zhang Shouzi , Yin Shufei , Ren Weicong , He Rongqiao , Li Juan
Published: July 2018

The triple network model that consists of the default‐mode network (DMN), central‐executive network (CEN), and salience network (SN) has been suggested as a powerful paradigm for investigation of network mechanisms underlying various cognitive functions and brain disorders. A crucial hypothesis in this model is that the fronto‐insular cortex (FIC) in the SN plays centrally in mediating interactions between the networks. Using a machine learning approach based on independent component analysis and Bayesian network (BN), this study characterizes the directed connectivity architecture of the triple network and examines the role of FIC in connectivity of the model. Data‐driven exploration shows that the FIC initiates influential connections to all other regions to globally control the functional dynamics of the triple network. Moreover, stronger BN connectivity between the FIC and regions of the DMN and the CEN, as well as the increased outflow connections from the FIC are found to predict individual performance in memory and executive tasks. In addition, the posterior cingulate cortex in the DMN was also confirmed as an inflow hub that integrates information converging from other areas. Collectively, the results highlight the central role of FIC in mediating the activity of large‐scale networks, which is crucial for individual cognitive function.
Evidence for a general performance‐monitoring system in the human brain
Authors: Zubarev Ivan , Parkkonen Lauri
Published: July 2018

Adaptive behavior relies on the ability of the brain to form predictions and monitor action outcomes. In the human brain, the same system is thought to monitor action outcomes regardless of whether the information originates from internal (e.g., proprioceptive) and external (e.g., visual) sensory channels. Neural signatures of processing motor errors and action outcomes communicated by external feedback have been studied extensively; however, the existence of such a general action‐monitoring system has not been tested directly. Here, we use concurrent EEG‐MEG measurements and a probabilistic learning task to demonstrate that event‐related responses measured by electroencephalography and magnetoencephalography display spatiotemporal patterns that allow an effective transfer of a multivariate statistical model discriminating the outcomes across the following conditions: (a) erroneous versus correct motor output, (b) negative versus positive feedback, (c) high‐ versus low‐surprise negative feedback, and (d) erroneous versus correct brain–computer‐interface output. We further show that these patterns originate from highly‐overlapping neural sources in the medial frontal and the medial parietal cortices. We conclude that information about action outcomes arriving from internal or external sensory channels converges to the same neural system in the human brain, that matches this information to the internal predictions.
4‐Quinolone Derivatives and Their Activities Against Gram‐negative Pathogens
Authors: Jiang Dan
Published: July 2018

Gram‐negative pathogens represent a significant global health threat, while the emergency and widespread of drug resistance make the situation even worse. As “privileged building blocks,” 4‐quinolones including fluoroquinolones are mainstays of chemotherapy against various bacterial infections. However, as other antibiotics, the resistance of Gram‐negative bacteria to 4‐quinolones develops rapidly and spreads widely throughout the world. To overcome the resistance and improve the potency, a number of 4‐quinolone derivatives were designed, synthesized, and screened for their in vitro and in vivo activities against representative Gram‐negative pathogens. This review aims to summarize the recent advances made towards the discovery of 4‐quinolone derivatives as anti‐Gram‐negative agents as well as their structure–activity relationship. The enriched structure–activity relationship paves the way to the further rational development of 4‐quinolones with excellent potency against both drug‐susceptible and drug‐resistant Gram‐negative pathogens.
Oxazole and Isoxazole Chemistry in Crop Protection
Authors: Lamberth Clemens
Published: July 2018

An overview is given of the significance of the oxazole and isoxazole scaffolds in crop protection chemistry. The main herbicidally, fungicidally, and insecticidally active oxazole and isoxazole classes are presented, together with their synthesis routes, modes of action, and biological efficacies. In addition, the role of oxazoles and isoxazoles as lead structure or as intermediate in the synthesis of other agrochemicals is reported. Also, partially and fully saturated oxazole and isoxazole derivatives such as oxazolines, isoxazolines, oxazolidines, and isoxazolidines, oxygenated derivatives such as oxazolones and isoxazolones as well as annulated derivatives, such as benzoxazoles and benzisoxazoles, are covered.
Organocatalyzed Synthesis and Antibacterial Activity of Novel Quinolino Annulated Analogues of Azepinones
Authors: Arora Deepika , Dwivedi Jaya , Arora Sakshi , Kumar Sudesh , Kishore Dharma
Published: July 2018

Starting from dimedone, two methodologies for synthesizing novel quinolino annulated azepinones have been reported. The protocol involves azepinone synthesis by the action of a newly synthesized organocatalyst derived from the reaction of TCT and DMF on oxime derivatives (5 and 9), which were obtained by the reaction of acridine dione derivatives (4 and 8) with hydroxylamine hydrochloride. The derivatives 4 and 8 were obtained by the reaction of 1 with anthranilic acid 2 and isatoic anhydride 7, respectively. The synthesis of all the compounds was confirmed initially by TLC followed by spectral analysis through IR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. The results that emanated on the evaluation of the antibacterial activity of azepinones against two Gram‐positive and two Gram‐negative test organisms using disc diffusion method have also been discussed. Compounds 6c, 6d, 6e, 10c, and 10e have been found to display better inhibitory activity than standard drugs streptomycin and tetracycline. The minimum inhibitory concentration and IC50 values for the compounds under study as well as of standard drugs were calculated. The maximum inhibition by bacterial strains was observed at 150 μg/mL.
Mass spectrometric detection of the Gibbs reaction for phenol analysis
Authors: Mistry Sabyasachy , Wenthold Paul G.
Published: July 2018

This paper describes a new method for detecting phenols, by reaction with Gibbs reagent to form indophenols, followed by mass spectrometric detection. Unlike the standard Gibbs reaction, which uses a colorometric approach, the use of mass spectrometry allows for simultaneous detection of differently substituted phenols. The procedure is demonstrated to work for a large variety of phenols without para‐substitution. With para‐substituted phenols, Gibbs products are still often observed, but the specific product depends on the substituent. For para groups with high electronegativity, such as methoxy or halogens, the reaction proceeds by displacement of the substituent. For groups with lower electronegativity, such as amino or alkyl groups, Gibbs products are observed that retain the substituent, indicating that the reaction occurs at the ortho or meta position. In mixtures of phenols, the relative intensities of the Gibbs products are proportional to the relative concentrations, and concentrations as low as 1 μmol/L can be detected. The method is applied to the qualitative analysis of commercial liquid smoke, and it is found that hickory and mesquite flavors have significantly different phenolic composition.
Postcolonial Theory and Humanism: A Framework for International Work in the Counseling Profession
Authors: SMITH PAUL H.
Published: July 2018

International work for U.S. counselors is expanding, but there is still limited theorizing about this work within the profession. Postcolonial theory offers a critical and deconstructive approach to international work that is congruent with historical features of the profession, namely humanism, while being responsive to the legacy of colonialism.
Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical
Authors: Thorpe Abbey A. , Bach Frances C. , Tryfonidou Marianna A. , Le Maitre Christine L. , Mwale Fackson , Diwan Ashish D. , Ito Keita
Published: July 2018

Chronic back and neck pain is a prevalent disability, often caused by degeneration of the intervertebral disc. Because current treatments for this condition are less than satisfactory, a great deal of effort is being applied to develop new solutions, including regenerative strategies. However, the path from initial promising idea to clinical use is fraught with many hurdles to overcome. Many of the keys to success are not necessarily linked to science or innovation. Successful translation to clinic will also rely on planning and awareness of the hurdles. It will be essential to plan your entire path to clinic from the outset and to do this with a multidisciplinary team. Take advice early on regulatory aspects and focus on generating the proof required to satisfy regulatory approval. Scientific demonstration and societal benefits are important, but translation cannot occur without involving commercial parties, which are instrumental to support expensive clinical trials. This will only be possible when intellectual property can be protected sufficiently to support a business model. In this manner, commercial, societal, medical, and scientific partners can work together to ultimately improve patient health. Based on literature surveys and experiences of the co‐authors, this opinion paper presents this pathway, highlights the most prominent issues and hopefully will aid in your own translational endeavors.
A note on decidability of variables in intuitionistic propositional logic
Authors: Ishii Katsumasa
Published: July 2018

An answer to the following question is presented: given a proof in classical propositional logic, for what small set of propositional variables p does it suffice to add all the formulae to Γ in order to intuitionistically prove A? This answer is an improvement of Ishihara's result for some cases.
Some properties of infinite factorials
Authors: Sonpanow Nattapon , Vejjajiva Pimpen
Published: July 2018

With the Axiom of Choice , for any infinite cardinal but, without , we cannot conclude any relationship between and for an arbitrary infinite cardinal . In this paper, we give some properties of in the absence of and compare them to those of for an infinite cardinal . Among our results, we show that “ for any infinite cardinal and any natural number n” is provable in although “ for any infinite cardinal ” is not.
Self‐Healing, Injectable Gelatin Hydrogels Cross‐Linked by Dynamic Schiff Base Linkages Support Cell Adhesion and Sustained Release of Antibacterial Drugs
Authors: Vahedi Mohammad , Barzin Jalal , Shokrolahi Fatemeh , Shokrollahi Parvin
Published: July 2018

A new class of dynamic hydrogels made through Schiff base bonds based on gelatin (type A and B) and polyethylene glycol dibenzaldehyde (diBA‐PEG, 2000 and 4000 g mol−1) is developed. Hydrogels form in situ by mixing aqueous solutions of gelatin and diBA‐PEG at a carefully adjusted pH. Compression test shows that the samples based on gelatin A are able to withstand at least ten cyclic loading/unloading without crack formation and significant permanent deformation. Self‐healing behavior of the hydrogel is proved by rheological measurements and also visual method. This hydrogel is proven to be injectable and nontoxic. Performance of the hydrogel in loading and delivery of clindamycin hydrochloride, as an antibacterial model drug, is evaluated against Staphylococcus aureus via antibacterial activity test. In vitro release of clindamycin hydrochloride is studied through an innovative method and it becomes clear that the release of clindamycin hydrochloride from this hydrogel follows a zero‐order kinetics.
Striped Bass and Atlantic Menhaden Predator–Prey Dynamics: Model Choice Makes the Difference
Authors: Uphoff James H. , Sharov Alexei
Published: July 2018

A version of multispecies virtual population analysis (MSVPA-X) had been the sole means of evaluating predation mortality by Striped Bass Morone saxatilis, Bluefish Pomatomus saltatrix, and Weakfish Cynoscion regalis on Atlantic Menhaden Brevoortia tyrannus during 1982–2008. Simplified models may offer a different view of predation, so we developed alternative estimates of predation mortality on Atlantic Menhaden with a simpler biomass dynamic predator–prey (Steele–Henderson or S–H) model. Strongly contrasting predictions of the importance of predation on age-1+ Atlantic Menhaden, particularly Striped Bass predation, emerged between the MSVPA-X and the S–H model. Striped Bass selected mostly age-0 and age-1 Atlantic Menhaden when modeled by MSVPA-X, even though large Striped Bass (>40% of biomass after the mid-1990s) were capable of consuming all ages. Consumption of Atlantic Menhaden by Striped Bass in the S–H model was drawn from aggregated age-1+ biomass. Combined predation mortality from Striped Bass, Bluefish, and Weakfish was well below fishing mortality for all but the earliest years in the MSVPA-X but was greater than or equivalent to fishing mortality throughout most of the S–H model time series. Striped Bass were a relatively minor source of Atlantic Menhaden predation mortality with the MSVPA-X but were the major source since the late 1990s in the S–H model. Annual estimates of Atlantic Menhaden biomass consumed per unit of Striped Bass biomass from the S–H model were roughly five times higher than MSVPA-X estimates and more consistent with estimates from bioenergetics models and trends of Striped Bass well-being indicators (tag-based natural mortality rates and weight at age). Use of an alternative S–H model provided a more complete picture of the potential range of predation pressure.
A likely pathogenic variant putatively affecting splicing of PIGA identified in a multiple congenital anomalies hypotonia‐seizures syndrome 2 (MCAHS2) family pedigree via whole‐exome sequencing
Authors: Yang Junli , Wang Qiong , Zhuo Qingcui , Tian Huiling , Li Wen , Luo Fang , Zhang Jinghui , Bi Dan , Peng Jing , Zhou Dong , Xin Huawei
Published: July 2018

Background

Glycosylphosphatidylinositol (GPI) anchoring is a special type of protein posttranslational modification, by which proteins with diverse function are attached to cell membrane through a covalent linkage between the protein and the glycolipid. Phosphatidylinositol glycan anchor biosynthesis class A (PIGA) is a key enzyme in GPI anchor biosynthesis, somatic mutations or genetic variants of which have been associated with paroxysmal nocturnal hemoglobinuria (PNH), or PIGA deficiency, respectively. More than 10 PIGA pathogenic or likely pathogenic variants have been reported in a wide spectrum of clinical syndromes of PIGA deficiency, including multiple congenital anomalies hypotonia‐seizures syndrome 2 (MCAHS2).

Methods

Whole‐exome sequencing (WES) was performed on two trios, that is., the proband's family and his affected maternal cousin's family, from a nonconsanguineous Chinese family pedigree with hypotonia‐encephalopathy‐seizures disease history and putative X‐linked recessive inheritance. Sanger sequencing for PIGA variant was performed on affected members as well as unaffected members in the family pedigree to verify its familial segregation.

Results

A novel likely pathogenic variant in PIGA was identified through comparative WES analysis of the two affected families. The single‐nucleotide substitution (NC_000023.9:g.15343279T>C) is located in intron 3 of the PIGA gene and within the splice acceptor consensus sequence (NM_002641.3:c.849‐5A>G). Even though we have not performed RNA studies, in silico tools predict that this intronic variant may alter normal splicing, causing a four base pair insertion which creates a frameshift and a premature stop codon at position 297 (NP_002632.1:p.(Arg283Serfs*15)). Sanger sequencing analysis of the extended family members confirmed the presence of the variant and its X‐linked inheritance.

Conclusion

WES data analysis along with familial segregation of a rare intronic variant are suggestive of a diagnosis of X‐liked PIGA deficiency with clinical features of MCAHS2.
Classification of breast lesions in ultrasonography using sparse logistic regression and morphology‐based texture features
Authors: Nemat Hoda , Fehri Hamid , Ahmadinejad Nasrin , Frangi Alejandro F. , Gooya Ali
Published: July 2018

Purpose

This work proposes a new reliable computer‐aided diagnostic (CAD) system for the diagnosis of breast cancer from breast ultrasound (BUS) images. The system can be useful to reduce the number of biopsies and pathological tests, which are invasive, costly, and often unnecessary.

Methods

The proposed CAD system classifies breast tumors into benign and malignant classes using morphological and textural features extracted from breast ultrasound (BUS) images. The images are first preprocessed to enhance the edges and filter the speckles. The tumor is then segmented semiautomatically using the watershed method. Having the tumor contour, a set of 855 features including 21 shape‐based, 810 contour‐based, and 24 textural features are extracted from each tumor. Then, a Bayesian Automatic Relevance Detection (ARD) mechanism is used for computing the discrimination power of different features and dimensionality reduction. Finally, a logistic regression classifier computed the posterior probabilities of malignant vs benign tumors using the reduced set of features.

Results

A dataset of 104 BUS images of breast tumors, including 72 benign and 32 malignant tumors, was used for evaluation using an eightfold cross‐validation. The algorithm outperformed six state‐of‐the‐art methods for BUS image classification with large margins by achieving 97.12% accuracy, 93.75% sensitivity, and 98.61% specificity rates.

Conclusions

Using ARD, the proposed CAD system selects five new features for breast tumor classification and outperforms state‐of‐the‐art, making a reliable and complementary tool to help clinicians diagnose breast cancer.
Single‐fiber F waves compared with conventional surface F waves, and their utility in detecting early diabetic neuropathy
Authors: Kamel Jordan , Knight‐Sadler ROry , Cook Mark , Roberts Leslie
Published: July 2018

Introduction: The single‐fiber F‐wave (SFF‐wave) technique assesses the entire length of single motor fibers using a concentric needle. Herein we investigated the utility of this approach in the detection of early diabetes‐related neuropathy, and compared it with the use of conventional surface F waves (CF waves). Methods: Sixteen patients with diabetes and either no neuropathy or mild neuropathy were assessed and compared with 16 age‐ and height‐matched control participants. Results: Both CF and SFF waves were abnormal in all 5 patients who had mild neuropathy. However, SFF waves demonstrated subclinical abnormalities in 7 of 11 patients (64%) with no neuropathy, whereas only 2 of these patients (18%) had prolonged CF waves. Minimum F‐wave latency was comparable between techniques, but maximum SFF‐wave latency was more frequently prolonged, as these delayed motor units were better isolated, rather than buried among summated CF‐wave responses. Discussion: SFF waves highlight the segmental involvement in diabetic neuropathy, and use of the SFF‐wave technique detects more abnormalities than with CF waves. Muscle Nerve 58: 665–670, 2018
Age-Specific Estimates Indicate Potential Deleterious Capture Effects and Low Survival of Stocked Juvenile Colorado Pikeminnow
Authors: Clark Scott R. , Conner Mary M. , Durst Scott L. , Franssen Nathan R.
Published: July 2018

Hatcheries and stocking programs have become necessary to repatriate or augment populations of imperiled fishes worldwide. Over nearly two decades, millions of endangered juvenile Colorado Pikeminnow Ptychocheilus lucius have been stocked into the San Juan River (Colorado, New Mexico, and Utah); however, recruitment of these individuals to adult life stages (age ≥6) remains low. Using a mark–recapture data set collected from annual riverwide electrofishing efforts between 2003 and 2016, we investigated apparent survival and capture probabilities of stocked Colorado Pikeminnow to identify age-specific bottlenecks contributing to this lack of recruitment. With relatively high capture rates, which averaged between 0.34 and 0.39 for the first 2 years after an individual's first encounter, our results indicated that survival was consistently less than 0.25 for young age-groups (i.e., ages 1–3), and no appreciable increase in survival occurred until fish had been in the river for at least 3 years (i.e., age ≥4+). Although age and capture effects were confounded for most age-groups, capture appeared to reduce apparent survival for age-2 fish by approximately 50%. The confounding effects of age, a completely hatchery-origin population, and extensive environmental alterations to the San Juan River make it difficult to disentangle factors associated with this overall reduced juvenile survival.
Recent Advances in Graphene Quantum Dots: Synthesis, Properties, and Applications
Authors: Haque Enamul , Kim Jeonghun , Malgras Victor , Reddy Kakarla Raghava , Ward Alister C. , You Jungmok , Bando Yoshio , Hossain Md. Shahriar A. , Yamauchi Yusuke
Published: July 2018

Here, an interesting, new 0D material is presented: graphene quantum dots. The new properties arising from quantum confinement and edge effects after converting 2D graphene into graphene quantum dots have attracted great interest in various disciplines, such as physics, biology, materials, and chemistry. Here, the recent technological advances in the field of graphene quantum dots reported in the literature on both a theoretical and an experimental basis are highlighted. Various synthesis methodologies and physical properties are discussed, along with their implementation in energy (supercapacitors, fuel cells, photovoltaic devices, light‐emitting diodes), biomedical (biosensors, drug delivery, bioimaging), and environmental applications.