bluuebunny/crossref_metadata_2025 huggingface dataset:
From Extension to Shortening: Tectonic Inversion Distributed in Time and Space in the Alboran Sea, Western Mediterranean
Authors: Martínez‐García Pedro , Comas Menchu , Lonergan Lidia , Watts Anthony B.
Published: September 2017

2D seismic reflection data tied to biostratigraphical and log information from wells in the central and southeastern Alboran Sea have allowed us to constrain the spatial and temporal distribution of rifting and inversion. Normal faults, tilted basement blocks, and growth wedges reveal a thinned continental crust that formed in response to NW‐SE extension. To the east, a secondary SW‐NE trend of extension affects the transitional crust adjacent to the oceanic Algerian Basin. The maximum thickness of syn‐rift sediments is ~3.5 km, and the oldest recorded deposits are Serravallian. The WNW‐ESE Yusuf fault formed a buttress separating and accommodating variable extension between two different tectonic domains: the thinned continental crust of Alboran and the oceanic spreading of the Algerian Basin. Late Tortonian to present‐day NW‐SE Africa/Eurasia plate convergence drove shortening and reactivation of some of the earlier extensional structures as reverse and strike‐slip faults, forming complex, compartmentalised subbasins. Tectonic inversion coexisted with the formation of new faults and folds. Inversion was partial along the Habibas Basin and Al‐Idrisi fault, but complete along the Alboran Ridge, where some SW‐NE trending faults were perpendicular to the recent NW‐SE plate convergence and were reactivated as thrusts. The WNW‐ESE Yusuf fault is oblique to the convergence vector, and therefore, reactivation is mainly expressed as transpressional deformation. Volcanic rocks intruded along the Alboran Ridge and Yusuf faults during the latest stages of extension formed rheological anisotropies that localised the later inversion.
Reply to Comments on “the Cenozoic Fold‐and‐Thrust Belt of Eastern Sardinia: Evidences from the Integration of Field Data With Numerically Balanced Geological Cross Section” by Arragoni et al. (2016)
Authors: Salvini F. , Arragoni S. , Cianfarra P. , Maggi M.
Published: September 2017

The comment by Berra et al. (2017) on the evidence of Alpine tectonics in Eastern Sardinia proposed by Arragoni et al. (2016) is based on the sedimentological interpretations of few local outcrops in a marginal portion of the study area. The Cenozoic Alpine fold‐and‐thrust setting, which characterizes this region, presents flat‐over‐flat shear planes acting along originally stratigraphic contacts, where stratigraphic continuity is obviously maintained. The ramp sectors present steeply dipping bedding attitudes, and there is no need to invoke and to force prograding clinoforms with unrealistic angles to justify them. The balanced geological cross section proposed by Arragoni et al. (2016) is fully supported by robust newly collected structural data and is compatible with the overall tectonic setting, while the interpretation proposed by Berra et al. (2017) lacks a detailed structural investigation. We believe that the partial application of the techniques available to modern geology may lead to incorrect interpretations, thus representing an obstacle for the progress of knowledge in the Earth sciences.
Role of Micro‐Topographic Variability on the Distribution of Inorganic Soil‐Nitrogen Age in Intensively Managed Landscape
Authors: Woo Dong K. , Kumar Praveen
Published: September 2017

How does the variability of topography structure the spatial heterogeneity of nutrient dynamics? In particular, what role does micro‐topographic depression play in the spatial and temporal dynamics of nitrate, ammonia, and ammonium? We explore these questions using the 3‐D simulation of their joint dynamics of concentration and age. To explicitly resolve micro‐topographic variability and its control on moisture, vegetation, and carbon‐nitrogen dynamics, we use a high‐resolution LiDAR data over an agricultural site under a corn‐soybean rotation in the Intensively Managed landscapes Critical Zone Observatory in the U.S. Midwest. We utilize a hybrid CPU‐GPU parallel computing architecture to reduce the computational cost associated with such high‐resolution simulations. Our results show that in areas that present closed topographic depressions, relatively lower nitrate concentration and age are observed compared to elsewhere. The periodic ponding in depressions increases the downward flux of water that carries more dissolved nitrate to the deeper soil layer. However, the variability in the depressions is relatively higher as a result of the episodic ponding pattern. When aggregate efflux from the soil domain at the bottom of the soil is considered, we find a gradual decrease in the age on the rising limb of nitrate efflux and a gradual increase on the falling limb. In addition, the age of the nitrate efflux ranges from 4 to 7 years. These are significantly higher as compared to the ages associated with a nonreactive tracer indicating that they provide an inaccurate estimate of residence time of a reactive constituent through the soil column.
100 days with scans of the same Catphan phantom on the same CT scanner
Authors: Husby Ellen , Svendsen Elisabeth D , Andersen Hilde K , Martinsen Anne Catrine T
Published: September 2017

Quality control (QC) of CT scanners is important to evaluate image quality and radiation dose. Different QC phantoms for testing image quality parameters on CT are commercially available, and Catphan phantoms are widely used for this purpose. More data from measured image quality parameters on CT are necessary to assess test methods, tolerance levels, and test frequencies. The aim of this study was to evaluate the stability of essential image quality parameters for axial and helical scans on one CT scanner over time. A Catphan 600 phantom was scanned on a Philips Ingenuity CT scanner for 100 days over a period of 6 months. At each day of testing, one helical scan covering the entire phantom and four axial scans covering four different modules in the phantom were performed. All images were uploaded into Image Owl for automatic analysis of CT numbers, modular transfer function (MTF), low‐contrast resolution, noise, and uniformity. In general, the different image quality parameters for both scan techniques were stable over time compared to given tolerance levels. Average measured CT numbers differed between axial and helical scans, while MTF was almost identical for helical and axial scans. Axial scans had better low‐contrast resolution and less noise than helical scans. The uniformity was relatively similar for axial and helical scans. Most standard deviations of measured values were larger for helical scans compared to axial scans. Test results in this study were stable over time for both scan techniques, but further studies on different CT scanners are required to confirm that this also holds true for other systems.
Potential proton and photon dose degradation in advanced head and neck cancer patients by intratherapy changes
Authors: Stützer Kristin , Jakobi Annika , Bandurska‐Luque Anna , Barczyk Steffen , Arnsmeyer Carolin , Löck Steffen , Richter Christian
Published: September 2017

Purpose

Evaluation of dose degradation by anatomic changes for head‐and‐neck cancer (HNC) intensity‐modulated proton therapy (IMPT) relative to intensity‐modulated photon therapy (IMRT) and identification of potential indicators for IMPT treatment plan adaptation.

Methods

For 31 advanced HNC datasets, IMPT and IMRT plans were recalculated on a computed tomography scan (CT) taken after about 4 weeks of therapy. Dose parameter changes were determined for the organs at risk (OARs) spinal cord, brain stem, parotid glands, brachial plexus, and mandible, for the clinical target volume (CTV) and the healthy tissue outside planning target volume (PTV). Correlation of dose degradation with target volume changes and quality of rigid CT matching was investigated.

Results

Recalculated IMPT dose distributions showed stronger degradation than the IMRT doses. OAR analysis revealed significant changes in parotid median dose (IMPT) and near maximum dose (D1ml) of spinal cord (IMPT, IMRT) and mandible (IMPT). OAR dose parameters remained lower in IMPT cases. CTV coverage (V95%) and overdose (V107%) deteriorated for IMPT plans to (93.4 ± 5.4)% and (10.6 ± 12.5)%, while those for IMRT plans remained acceptable. Recalculated plans showed similarly decreased PTV conformity, but considerable hotspots, also outside the PTV, emerged in IMPT cases. Lower CT matching quality was significantly correlated with loss of PTV conformity (IMPT, IMRT), CTV homogeneity and coverage (IMPT). Target shrinkage correlated with increased dose in brachial plexus (IMRT, IMPT), hotspot generation outside the PTV (IMPT) and lower PTV conformity (IMRT).

Conclusions

The study underlines the necessity of precise positioning and monitoring of anatomy changes, especially in IMPT which might require adaptation more often. Since OAR doses remained typically below constraints, IMPT plan adaptation will be indicated by target dose degradations.
Improved Performance in FeF2 Conversion Cathodes through Use of a Conductive 3D Scaffold and Al2O3 ALD Coating
Authors: Kim Sanghyeon , Liu Jinyun , Sun Ke , Wang Junjie , Dillon Shen J. , Braun Paul V.
Published: September 2017

FeF2 is considered a promising conversion compound for the positive electrode in lithium‐ion batteries due to its high thermodynamic reduction potential (2.66 V vs Li/Li+) and high theoretical specific capacity (571 mA h g−1). However, the sluggish reaction kinetics and rapid capacity decay caused by side reactions during cycling limit its practical application. Here, the fabrication of Ni‐supported 3D Al2O3‐coated FeF2 electrodes is presented, and it is shown that these structured electrodes significantly overcome these limitations. The electrodes are prepared by iron electrodeposition on a Ni support, followed by a facile fluorination process and Al2O3 coating by atomic layer deposition. The 3D FeF2 electrode delivers an initial discharge capacity of 380 mA h g−1 at a current density of 200 mA g−1 at room temperature. The 3D scaffold improves the reaction kinetics and enables a high specific capacity by providing an efficient electron pathway to the insulating FeF2 and short Li diffusion lengths. The Al2O3 coating significantly improves the cycle life, probably by preventing side reactions through limiting direct electrode–electrolyte contact. The fabrication method presented here can also be applied for synthesis of other metal fluoride materials on different 3D conductive templates.
Highly Sensitive Detection of Protein Biomarkers with Organic Electrochemical Transistors
Authors: Fu Ying , Wang Naixiang , Yang Anneng , Law Helen Ka‐wai , Li Li , Yan Feng
Published: September 2017

The analysis of protein biomarkers is of great importance in the diagnosis of diseases. Although many convenient and low‐cost electrochemical approaches have been extensively investigated, they are not sensitive enough in the detection of protein biomarkers with low concentrations in physiological environments. Here, this study reports a novel organic‐electrochemical‐transistor‐based biosensor that can successfully detect cancer protein biomarkers with ultrahigh sensitivity. The devices are operated by detecting electrochemical activity on gate electrodes, which is dependent on the concentrations of proteins labeled with catalytic nanoprobes. The protein sensors can specifically detect a cancer biomarker, human epidermal growth factor receptor 2, down to the concentration of 10−14 g mL−1, which is several orders of magnitude lower than the detection limits of previously reported electrochemical approaches. Moreover, the devices can successfully differentiate breast cancer cells from normal cells at various concentrations. The ultrahigh sensitivity of the protein sensors is attributed to the inherent amplification function of the organic electrochemical transistors. This work paves a way for developing highly sensitive and low‐cost biosensors for the detection of various protein biomarkers in clinical analysis in the future.
Two‐Step Synthesis of Hierarchical Dual Few‐Layered Fe3O4/MoS2 Nanosheets and Their Synergistic Effects on Lithium‐Storage Performance
Authors: Lu Feifei , Xu Chunbo , Meng Fuchang , Xia Tian , Wang Ruihong , Wang Jingping
Published: September 2017

Owing to unique lamellar nanostructures, 2D inorganic materials are considered as promising candidates in energy storage and conversion. In this paper, a facile two‐step synthesis is developed to fabricate 3D hierarchical dual Fe3O4/MoS2 nanosheets (HD‐FMNs), in which few‐layered MoS2 nanosheets are anchored in 3D Fe3O4 nanosheet network to form the heterojunction structure. Furthermore, it is proved that the synergistic effects on both electron/lithium‐ion transport kinetics and mechanical cycling stability benefit from Fe3O4/MoS2 nanosheet incorporation in 3D HD‐FMN anode for lithium‐ion batteries (LIBs), resulting in the dramatically enhanced performance. The Fe3O4 nanosheet incorporation effectively improves the electronic conductivity due to its half‐metal characteristic, while the defect‐rich structure in the MoS2 nanosheets can facilitate the lithium ion transport. When tested as potential anode materials, 3D HD‐FMNs exhibit a high reversible capacity (650 mAh g−1) at current rate of 5 C (1 C = 1 A g−1) after superior long‐term cycles (1000 times), as well as an excellent rate capability even at high current rates. The outstanding electrochemical property of 3D HD‐FMNs allows their application in high‐performance anode materials for next‐generation LIBs. This strategy also opens a new way to design the novel 2D composite materials for electrochemical devices.
Low‐Temperature Mullite Formation in Ternary Oxide Coatings Deposited by ALD for High‐Temperature Applications
Authors: Furlan Kaline P. , Krekeler Tobias , Ritter Martin , Blick Robert , Schneider Gerold A. , Nielsch Kornelius , Zierold Robert , Janßen Rolf
Published: September 2017

Atomic layer deposition (ALD) process presents thickness control in an Ångstrom scale due to its inherent surface self‐limited reactions. In this work, an ALD super cycle approach, where a superposition of nanolaminates of SiO2 and Al2O3 is generated by cycling the precursors APTES–H2O–O3 and TMA–H2O, is used to deposit thin films with varying ratio of Al2O3:SiO2 into silicon wafers and into inverse photonic crystals. The resulting ternary oxide films deposited at low temperature (150 °C) are amorphous. However, conversion to mullite occurs at 1000 °C, way below the conversion temperatures found into powder processing or diphasic sol–gel routes (type II) and comparable to monophasic sol–gel synthesis. By means of such a mullite coating, the structural stability of an Al2O3 inverse photonic crystal is increased up to 1400 °C.
Self‐Assembled Silver–Germanium Nanolayer Metamaterial with the Enhanced Nonlinear Response
Authors: Stefaniuk Tomasz , Olivier Nicolas , Belardini Alessandro , McPolin Cillian P. T. , Sibilia Concita , Wronkowska Aleksandra A. , Wronkowski Andrzej , Szoplik Tomasz , Zayats Anatoly V.
Published: September 2017

Plasmonic metamaterials and metasurfaces are important for many linear and nonlinear photonic applications. Here, the possibility to control a nanostructured layer spontaneously formed near an interface of a thin silver film is shown, where the interplay between a grain boundary structure and surface segregation of germanium atoms leads to encapsulation of the grains and, as the result, formation of a composite metamaterial near the film surface. This Ag/Ge composite exhibits strong localized surface plasmon resonances at Ge‐encapsulated silver grains, leading to extraordinary second harmonic generation for both transverse magnetic and transverse electric polarized fundamental light with up to two orders of magnitude enhancement compared to thin Ag films without Ge atoms. Segregation phenomena open the possibility for fabrication of a new class of composite materials and gives additional degree of freedom in designing optical properties of nanostructured metamaterials.
Rh(II)‐Catalyzed Tandem Cyclization of Aliphatic N‐Sulfonyl‐1,2,3‐triazoles and Alcohols for the Synthesis of 6‐Alkoxy Piperidin‐3‐ones
Authors: Zhang Ran , Li Yang , Ali Arshad , Hao Jiamin , Bi Xihe , Fu Junkai
Published: September 2017

A diastereoselective synthesis of 6‐alkoxy piperidin‐3‐ones based on a novel Rh(II)‐catalyzed tandem cyclization of aliphatic N‐sulfonyl triazoles and alcohols is reported herein for the first time, which provides a facile entry into piperidinones bearing quaternary carbons at C4 or C5 position. By employing an external chiral alcohol, the asymmetric version of the reaction has been realized.

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Palladium‐catalyzed Oxa‐[4+2] Annulation of para‐Quinone Methides
Authors: Yuan Zhenbo , Pan Rui , Zhang He , Liu Lina , Lin Aijun , Yao Hequan
Published: September 2017

A palladium‐catalyzed oxa‐[4+2] annulation of para‐quinone methides with allyl carbonates bearing a nucleophilic alcohol side chain has been developed. This method provided an efficient strategy to the construction of 2‐oxaspiro‐cyclohexadienones via 1,6‐conjugated addition‐mediated allylation in moderate to good yields. Preliminary results on asymmetric derivatives promised potential in the synthesis of enantioenriched frameworks.

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The evaluation of stretchability and its applications for biaxially oriented polypropylene film
Authors: Kanai Toshitaka , Egoshi Kentaro , Ohno Satoshi , Takebe Tomoaki
Published: September 2017

In recent years, plastic film is essential in our daily lives. Among them, polypropylene has good physical properties, for example, tensile strength, impact strength, and transparency. Recently, it was found that the stretchability of polypropylene (PP) is improved by blending a small amount of low modulus polypropylene (LMPP) which is a low tacticity polypropylene. The purpose of this research was to investigate the effect of blending LMPP, which has different characteristic of resin such as tacticity and molecular weight, on PP and to study the mechanism of the structure formation in a biaxial stretching process. The blending of LMPP to PP reduces the spherulite size and increases the thickness of the amorphous phase in the lamella without changing the thickness of the crystal phase, namely the melting temperature. LMPP blends also reduced the yield stress during the stretching process and increased the stress buildup ratio. For these reasons, it improved film thickness uniformity of biaxially stretched film and reduced film break during the high production line. Furthermore, as the stretchable temperature window was widened to the low‐temperature side, the thickness uniformity was improved in the wide stretchable temperature. As a result, improving the stretchability and the film thickness uniformity of PP were achieved by blending LMPP to PP.
Wear performance of multiwalled carbon nanotube‐reinforced ultra‐high molecular weight polyethylene composite
Authors: Camacho Nayeli , Franco‐Urquiza Edgar A. , Stafford Stephen W.
Published: September 2017

Ultra‐high molecular weight polyethylene (UHMWPE) has proven to be a good counterpart articulating surface against Cr–Co–Mo femoral components in artificial joints. Nevertheless, UHMWPE wear damage and subsequent aseptic loosening continues to be the main reason for revision of knee replacements. There is an ongoing research effort to improve the metal‐on‐UHMWPE couple. This study compares the wear resistance of multiwalled carbon nanotube‐reinforced UHMWPE composite with conventional orthopedic grade UHMWPE currently used in total knee replacements. Defined by previous studies, 1.25 wt.% multiwall carbon nanotubes (MWCNT) were incorporated into UHMWPE to fabricate UHMWPE‐MWCNT composites by solution blending, achieving an even distribution in the polymeric matrix. UHMWPE‐MWCNT samples were manufactured by compression molding and sterilized with γ‐rays. Scanning electron microscopy confirmed a uniform distribution of the MWCNTs. The volumetric wear was reduced by 86.9%, and the indentation depth in creep testing decreased 68%. The composite displayed superior wear behavior producing less wear debris than conventional materials.
Recent Progress in Electrocatalyst for Li‐O2 Batteries
Authors: Chang Zhiwen , Xu Jijing , Zhang Xinbo
Published: September 2017

In the Li‐O2 field, the electrocatalyst plays an important role in accelerating the sluggish electrochemical reactions, thus improving the performances of Li‐O2 battery. In this field, numerous researches regarding the incorporation of electrocatalyst have been published. With the aim to provide an easy as well as timely access for readers to follow the latest development in the catalyst area, the progress regarding the recent development on the application and research of electrocatalyst for Li‐O2 batteries is reviewed in a comprehensive and systematic manner. The application of various kinds of electrocatalyst including solid catalyst and soluble catalyst is first summarized. Then, relevant research including the catalyst design and the correlation between the catalyst property and the Li‐O2 battery performance is discussed. Finally, insights on how to fabricate an effective electrocatalyst are provided, which are expected to provide guidance for further catalyst design.
Single‐Crystalline Ultrathin Co3O4 Nanosheets with Massive Vacancy Defects for Enhanced Electrocatalysis
Authors: Cai Zhao , Bi Yongmin , Hu Enyuan , Liu Wen , Dwarica Nico , Tian Yang , Li Xiaolin , Kuang Yun , Li Yaping , Yang Xiao‐Qing , Wang Hailiang , Sun Xiaoming
Published: September 2017

The role of vacancy defects is demonstrated to be positive in various energy‐related processes. However, introducing vacancy defects into single‐crystalline nanostructures with given facets and studying their defect effect on electrocatalytic properties remains a great challenge. Here this study deliberately introduces oxygen defects into single‐crystalline ultrathin Co3O4 nanosheets with O‐terminated {111} facets by mild solvothermal reduction using ethylene glycol under alkaline condition. As‐prepared defect‐rich Co3O4 nanosheets show a low overpotential of 220 mV with a small Tafel slope of 49.1 mV dec−1 for the oxygen evolution reaction (OER), which is among the best Co‐based OER catalysts to date and even more active than the state‐of‐the‐art IrO2 catalyst. Such vacancy defects are formed by balancing with reducing environments under solvothermal conditions, but are surprisingly stable even after 1000 cycles of scanning under OER working conditions. Density functional theory plus U calculation attributes the enhanced performance to the oxygen vacancies and consequently exposed second‐layered Co metal sites, which leads to the lowered OER activation energy of 2.26 eV and improved electrical conductivity. This mild solvothermal reduction concept opens a new door for the understanding and future designing of advanced defect‐based electrocatalysts.
Taking Your Qualitative Research to the Next Level: A Guide for the Medical Educator
Authors: Schneider Nancy C. , Coates Wendy C. , Yarris Lalena M.
Published: September 2017

Qualitative research is a focused and deliberate approach to understanding the human condition and can identify areas that warrant further investigation through hypothesis‐testing (quantitative) research. In this overview article, we discuss reasons to undertake a qualitative study; introduce three research paradigms whose frameworks are commonly used by medical education researchers (grounded theory, ethnography, phenomenology); describe the four most commonly used data gathering techniques (interviews, focus groups, observation, document tracing); and discuss the nature of the sampling/data gathering process. Examples of research questions that employ each paradigm and data gathering technique as well as a list of published sample articles to guide researchers are provided.
To Serve or Not to Serve: Ethical and Policy Implications
Authors: Jason Leonard A.
Published: September 2017

The Institute of Medicine (IOM) is one of the nation's more influential health‐related non‐profit organizations. It plays a large role in shaping health policy by commissioning panels to develop “white papers” describing research and recommendations on a variety of health topics. These white paper publications are often used to help make policy decisions at the legislative and executive levels. Such a prominent institution might seem like a natural ally for policy‐related collaborative efforts. As community psychologists, we strongly endorse efforts to positively influence public policy at the national level. However, while serving on influential panels and commissions like the IOM might seem to be very much part of the ethos of our discipline, there are occasions when such institutions are pursuing a mission that inadvertently has the potential to instigate divisive friction among community activists and organizations. A case study is presented whereby I describe my decision not to accept an invitation to serve on a controversial IOM panel. I explore the ethical challenges regarding maintaining my independence from this institution and its attempt to redefine chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME), as well as the process of searching for alternative avenues for collaborating with community activists to influence policy related to these debilitating illnesses.
Evaluating real‐time effects of topical 1:1000 epinephrine in endoscopic sinus and skull‐base surgery on hemodynamic parameters through intraoperative arterial line monitoring
Authors: Yim Michael T. , Ahmed Omar G. , Takashima Masayoshi
Published: September 2017

Background

Administration of topical 1:1000 epinephrine is commonly used in practice to achieve vasoconstriction during endoscopic sinus surgery and skull‐base surgery; however, real‐time effects on cardiovascular changes from systemic absorption have not been well studied.

Methods

Twenty‐six patients undergoing endoscopic transsphenoidal resection of a pituitary lesion at a single institution were included into the study. Following arterial line placement by anesthesiology, 6 cottonoid pledgets soaked in 1:1000 epinephrine were placed into the bilateral nasal passages. Hemodynamic parameters including heart rate, blood pressure, and mean arterial pressure were collected at baseline, 30 seconds, and increments in minutes up to 10 minutes. Additional potentially confounding factors such as use of antihypertensives, stress dose steroids, and positioning with head pins were all performed following termination of data collection.

Results

The majority of patients (20/26, 77%) showed no significant change in any parameter following placement of epinephrine soaked cottonoids. Six patients, however, had transient increases in blood pressure following administration of topical epinephrine, with a few requiring vasodilatory interventions. Return to baseline cardiovascular values were noted after an average of 7 minutes. There was no correlative preoperative characteristic that predicted sensitivity to placement of epinephrine. There were no lasting or permanent effects.

Conclusion

Although intranasal topical 1:1000 epinephrine use showed no substantial hemodynamic changes in the majority of patients, in a subset of patients it can cause significant transient elevations in blood pressure to a degree necessitating intervention. Topical epinephrine should be used judiciously in endoscopic sinus surgery.
Benford's law: A “sleeping beauty” sleeping in the dirty pages of logarithmic tables
Authors: Mir Tariq Ahmad , Ausloos Marcel
Published: September 2017

Benford's law is an empirical observation, first reported by Simon Newcomb in 1881 and then independently by Frank Benford in 1938: the first significant digits of numbers in large data are often distributed according to a logarithmically decreasing function. Being contrary to intuition, the law was forgotten as a mere curious observation. However, in the last two decades relevant literature has grown exponentially—an evolution typical of “Sleeping Beauties” (SBs) publications that go unnoticed (sleep) for a long time and then suddenly become the center of attention (are awakened). Thus, in the present study, we show that the two papers, Newcomb () and Benford (), Newcomb (, American Journal of Mathematics, 4, 39–40) and Benford (1938, Proc. Am. Phil. Soc., 78, 551–572) papers are clearly SBs. The former was in a deep sleep for 110 years, whereas the latter was in a deep sleep for a comparatively lesser period of 31 years up to 1968, and in a state of less deep sleep for another 27 years, up to 1995. Both SBs were awakened in the year 1995 by Hill (, Statistical Science, 10, 354–363). In so doing, we show that the waking prince (Hill, ) is more often quoted than the SB whom he kissed—in this Benford's law case, wondering whether this is a general effect—to be usefully studied.
Stimulus‐Induced Conformational Transformation of a Cyclic Peptide for Selective Cell‐Targeting On–Off Gatekeeper for Mesoporous Nanocarriers
Authors: Lee Jeonghun , Oh Eun‐Taex , Song Jaehun , Kim Ha Gyeong , Park Heon Joo , Kim Chulhee
Published: September 2017

αvβ3 Integrin is upregulated on many cancer cells. We designed a dual functional cyclic peptide gatekeeper with a capability of stimuli‐responsive conformational transformation which could serve as a selective cell‐targeting on–off gatekeeper for mesoporous nanocarriers. The advantage of employing the motif of stimuli‐induced conformational transformation of cyclic peptides is that they could be utilized not only as an on–off gatekeeper for the triggered release of cargo drugs but also as a targeting ligand of the carriers to desired cells with their respective binding receptors. The peptide gatekeepers on the surface of nanocarriers exhibited on–off gatekeeping via conformational transformation triggered by intracellular glutathione levels of the cancer cells. The cyclic RGD sequence of the peptide gatekeepers enhanced the intracellular uptake into tumor cells (A549) and the therapeutic efficacy of the nanocarrier.
ΔFlucs: Brighter Photinus pyralis firefly luciferases identified by surveying consecutive single amino acid deletion mutations in a thermostable variant
Authors: Halliwell Lisa M. , Jathoul Amit P. , Bate Jack P. , Worthy Harley L. , Anderson James C. , Jones D. Dafydd , Murray James A.H.
Published: September 2017

The bright bioluminescence catalyzed by Photinus pyralis firefly luciferase (Fluc) enables a vast array of life science research such as bio imaging in live animals and sensitive in vitro diagnostics. The effectiveness of such applications is improved using engineered enzymes that to date have been constructed using amino acid substitutions. We describe ΔFlucs: consecutive single amino acid deletion mutants within six loop structures of the bright and thermostable ×11 Fluc. Deletion mutations are a promising avenue to explore new sequence and functional space and isolate novel mutant phenotypes. However, this method is often overlooked and to date there have been no surveys of the effects of consecutive single amino acid deletions in Fluc. We constructed a large semi‐rational ΔFluc library and isolated significantly brighter enzymes after finding ×11 Fluc activity was largely tolerant to deletions. Targeting an “omega‐loop” motif (T352‐G360) significantly enhanced activity, altered kinetics, reduced Km for D‐luciferin, altered emission colors, and altered substrate specificity for redshifted analog DL‐infraluciferin. Experimental and in silico analyses suggested remodeling of the Ω‐loop impacts on active site hydrophobicity to increase light yields. This work demonstrates the further potential of deletion mutations, which can generate useful Fluc mutants and broaden the palette of the biomedical and biotechnological bioluminescence enzyme toolbox.
Development of a formaldehyde biosensor with application to synthetic methylotrophy
Authors: Woolston Benjamin M. , Roth Timothy , Kohale Ishwar , Liu David R. , Stephanopoulos Gregory
Published: September 2017

Formaldehyde is a prevalent environmental toxin and a key intermediate in single carbon metabolism. The ability to monitor formaldehyde concentration is, therefore, of interest for both environmental monitoring and for metabolic engineering of native and synthetic methylotrophs, but current methods suffer from low sensitivity, complex workflows, or require expensive analytical equipment. Here we develop a formaldehyde biosensor based on the FrmR repressor protein and cognate promoter of Escherichia coli. Optimization of the native repressor binding site and regulatory architecture enabled detection at levels as low as 1 µM. We then used the sensor to benchmark the in vivo activity of several NAD‐dependent methanol dehydrogenase (Mdh) variants, the rate‐limiting enzyme that catalyzes the first step of methanol assimilation. In order to use this biosensor to distinguish individuals in a mixed population of Mdh variants, we developed a strategy to prevent cross‐talk by using glutathione as a formaldehyde sink to minimize intercellular formaldehyde diffusion. Finally, we applied this biosensor to balance expression of mdh and the formaldehyde assimilation enzymes hps and phi in an engineered E. coli strain to minimize formaldehyde build‐up while also reducing the burden of heterologous expression. This biosensor offers a quick and simple method for sensitively detecting formaldehyde, and has the potential to be used as the basis for directed evolution of Mdh and dynamic formaldehyde control strategies for establishing synthetic methylotrophy.
Helical Threads: Enantiomerically Pure Carbo[6]Helicene Oligomers
Authors: Schaack Cédric , Sidler Eric , Trapp Nils , Diederich François
Published: September 2017

We report the synthesis of enantiomerically pure carbo[6]helicene oligomers with buta‐1,3‐diyne‐1,4‐diyl bridges between the helicene nuclei. The synthesis of monomeric (±)‐2,15‐bis[(triisopropylsilyl)ethynyl]carbo[6]helicene was achieved in 25 % yield over six steps. Pure (+)‐(P)‐ and (−)‐(M)‐enantiomers were obtained by HPLC on a chiral stationary phase. The dimeric (+)‐(P)2‐ and (−)‐(M)2‐configured and the tetrameric (+)‐(P)4‐ and (−)‐(M)4‐configured oligomers were obtained by sequential oxidative acetylenic coupling. The ECD spectra of the tetrameric oligomers displayed large Cotton effect intensities of Δϵ=−851 m−1 cm−1 at λ=370 nm ((M)4‐enantiomer). We transformed the buta‐1,3‐diyne‐1,4‐diyl bridge in the dimeric (P)2 and (M)2 oligomer by heteroaromatization into a thiene‐2,5‐diyl linker. Although the resulting chromophore showed reduced ECD intensities, it exhibited a remarkably strong fluorescence emission at 450–500 nm, with an absolute quantum yield of 25 %.
Organoruthenium Complexes with C^N Ligands are Highly Potent Cytotoxic Agents that Act by a New Mechanism of Action
Authors: Novohradsky Vojtech , Yellol Jyoti , Stuchlikova Olga , Santana María Dolores , Kostrhunova Hana , Yellol Gorakh , Kasparkova Jana , Bautista Delia , Ruiz José , Brabec Viktor
Published: September 2017

Our study demonstrates that four novel kinetically inert C,N‐cyclometalated RuII complexes of the type [Ru(C^N)(N^N)2][PF6] containing a handle for functionalization on the C^N ligand are very potent cytotoxic agents against several different human cancer cell lines and are up to 400‐fold more potent than clinically used cisplatin. In addition, the investigated ruthenium complexes are less cytotoxic in noncancerous cells, and exhibit higher selectivity for cancer cells than conventional platinum anticancer drugs. The high potency of the investigated ruthenium compounds can be attributed to several factors, including enhanced internalization and their capability to change mitochondrial transmembrane potential in cells. The new ruthenium complexes also interfere with protein synthesis with a markedly higher potency than conventional inhibitors of DNA translation. Notably, the latter mechanism has not been hitherto described for other cytotoxic Ru compounds and cisplatin.
Isoform specificity of progesterone receptor antibodies
Authors: Fabris Victoria , Abascal María F , Giulianelli Sebastián , May María , Sequeira Gonzalo R , Jacobsen Britta , Lombès Marc , Han Julie , Tran Luan , Molinolo Alfredo , Lanari Claudia
Published: September 2017

Progesterone receptors (PR) are prognostic and predictive biomarkers in hormone‐dependent cancers. Two main PR isoforms have been described, PRB and PRA, that differ only in that PRB has 164 extra N‐terminal amino acids. It has been reported that several antibodies empirically exclusively recognize PRA in formalin‐fixed paraffin‐embedded (FFPE) tissues. To confirm these findings, we used human breast cancer xenograft models, T47D‐YA and ‐YB cells expressing PRA or PRB, respectively, MDA‐MB‐231 cells modified to synthesize PRB, and MDA‐MB‐231/iPRAB cells which can bi‐inducibly express either PRA or PRB. Cells were injected into immunocompromised mice to generate tumours exclusively expressing PRA or PRB. PR isoform expression was verified using immunoblots. FFPE samples from the same tumours were studied by immunohistochemistry using H‐190, clone 636, clone 16, and Ab‐6 anti‐PR antibodies, the latter exclusively recognizing PRB. Except for Ab‐6, all antibodies displayed a similar staining pattern. Our results indicate that clones 16, 636, and the H‐190 antibody recognize both PR isoforms. They point to the need for more stringency in evaluating the true specificity of purported PRA‐specific antibodies as the PRA/PRB ratio may have prognostic and predictive value in breast cancer.
Inverted formins: A subfamily of atypical formins
Authors: Hegsted Anna , Yingling Curtis V. , Pruyne David
Published: September 2017

Formins are a family of regulators of actin and microtubule dynamics that are present in almost all eukaryotes. These proteins are involved in many cellular processes, including cytokinesis, stress fiber formation, and cell polarization. Here we review one subfamily of formins, the inverted formins. Inverted formins as a group break several formin stereotypes, having atypical biochemical properties and domain organization, and they have been linked to kidney disease and neuropathy in humans. In this review, we will explore recent research on members of the inverted formin sub‐family in mammals, zebrafish, fruit flies, and worms.
The morphological characterization of orientation‐biased displaced large‐field ganglion cells in the central part of goldfish retina
Authors: Hoshi Hideo , Sato Fumi
Published: September 2017

The vertebrate retina has about 30 subtypes of ganglion cells. Each ganglion cell receives synaptic inputs from specific types of bipolar and amacrine cells ramifying at the same depth of the inner plexiform layer (IPL), each of which is thought to process a specific aspect of visual information. Here, we identified one type of displaced ganglion cell in the goldfish retina which had a large and elongated dendritic field. As a population, all of these ganglion cells were oriented in the horizontal axis and perpendicular to the dorsal–ventral axis of the goldfish eye in the central part of retina. This ganglion cell has previously been classified as Type 1.2. However, the circuit elements which synapse with this ganglion cell are not yet characterized. We found that this displaced ganglion cell was directly tracer‐coupled only with homologous ganglion cells at sites containing Cx35/36 puncta. We further illustrated that the processes of dopaminergic neurons often terminated next to intersections between processes of ganglion cells, close to where dopamine D1 receptors were localized. Finally, we showed that Mb1 ON bipolar cells had ribbon synapses in the axonal processes passing through the IPL and made ectopic synapses with this displaced ganglion cell that stratified into stratum 1 of the IPL. These results suggest that the displaced ganglion cell may synapse with both Mb1 cells using ectopic ribbon synapses and OFF cone bipolar cells with regular ribbon synapses in the IPL to function in both scotopic and photopic light conditions.
A comparative study of the class imbalance problem in Twitter spam detection
Authors: Li Chaoliang , Liu Shigang
Published: September 2017

Recently, online social network (OSN) such as Twitter has become an important and popular source for real‐time information and news dissemination, and Twitter is inevitably a prime target of spammers. It has been showed that the security threats caused by Twitter spam can reach far beyond the social media platform itself. To mitigate the damage caused by Twitter spam, machine learning classification algorithms have been employed by researchers and communities to detect the Twitter spam. However, most of these studies have overlooked the class imbalance problem in Twitter spam detection. In this paper, we have studied the class imbalance problem in Twitter spam detection. Firstly, we have conducted a comparative study regarding some popular methods in handling the class imbalance problem in order to identify the most effective approach for addressing the class imbalance problem. Then, we have conducted another comparative study from Twitter spam detection based on several classic techniques. Experimental results demonstrate that a fuzy‐based ensemble learning can significantly improve the classification performance on imbalance ground truth Twitter data.
Vibration Ball Milling for the Synthesis of 5′‐Thioadenosine 5′‐Pyrophosphate (P′→5′) Adenosine (dASppA)
Authors: Eguaogie Olga , Vyle Joseph S.
Published: September 2017

Using vibration ball milling, 5′‐chloro‐5′‐deoxyadenosine (CldA) reacts cleanly with 4‐methoxybenzyl mercaptan (MobSH), under basic conditions, to the corresponding thioether (MobSdA), which is isolated following precipitation and trituration. Under acidic conditions, in a one‐pot, two‐step process, MobSdA is transformed into 5′‐deoxy‐5′‐(5‐nitropyridyl‐2‐disulfanyl)‐adenosine (NPySSdA). Michaelis‐Arbuzov (M‐A) reaction of NPySSdA with tris(trimethylsilyl) phosphite proceeds to completion within 30 min as determined by 31P NMR, and the persilylated M‐A product thus formed can be stored in solution under anhydrous conditions at room temperature for several days (in contrast, the anionic phosphorothiolate monoester is labile to hydrolysis). Following evaporation, mechanochemical mixing of the crude M‐A product with the nucleotide donor adenosine 5′‐monophosphomorpholidate under acidic activation in the presence of additional water gives rapid hydrolytic desilylation and phosphate coupling, so that essentially complete reaction is observed after 90 min and dASppA isolated following C‐18 reversed phase HPLC and desalting (>99% pure as determined by monitoring at 260 nm). © 2017 by John Wiley & Sons, Inc.
Solid‐Phase Synthesis of RNA Analogs Containing Phosphorodithioate Linkages
Authors: Yang Xianbin
Published: September 2017

The oligoribonucleotide phosphorodithioate (PS2‐RNA) modification uses two sulfur atoms to replace two non‐bridging oxygen atoms at an internucleotide phosphorodiester backbone linkage. Like a natural phosphodiester RNA backbone linkage, a PS2‐modified backbone linkage is achiral at phosphorus. PS2‐RNAs are highly stable to nucleases and several in vitro assays have demonstrated their biological activity. For example, PS2‐RNAs silenced mRNA in vitro and bound to protein targets in the form of PS2‐aptamers (thioaptamers). Thus, the interest in and promise of PS2‐RNAs has drawn attention to synthesizing, isolating, and characterizing these compounds. RNA‐thiophosphoramidite monomers are commercially available from AM Biotechnologies and this unit describes an effective methodology for solid‐phase synthesis, deprotection, and purification of RNAs having PS2 internucleotide linkages. © 2017 by John Wiley & Sons, Inc.
Is 2‐Hydroxypropyl‐β‐cyclodextrin a Suitable Carrier for Central Administration of Δ9‐Tetrahydrocannabinol? Preclinical Evidence
Authors: Agabio R. , Sanna F. , Lobina C. , Monduzzi M. , Nairi V. , Cugia F. , Mameli S. , Pisanu G. M. , Gessa G. L. , Melis M. R.
Published: September 2017

Preclinical Research

Δ9‐Tetrahydrocannabinol (THC) is a hydrophobic compound that has a potent antinociceptive effect in animals after intrathecal (IT) or intracerebroventricular (ICV) administration. The lack of a suitable solvent precludes its IT administration in humans. 2‐Hydroxypropyl‐β‐cyclodextrin (HPβCD) increases the water solubility of hydrophobic drugs and is approved for IT administration in humans. To investigate whether HPβCD might be a suitable carrier for ICV administration of THC in rats, two formulations containing THC complexed with HPβCD (30 and 135 μg of THC per animal) and vehicle were administered to Wistar rats. The antinociceptive effect (using the tail flick test), locomotor activity, and body temperature were evaluated. ICV injection of 135 μg of THC/HPβCD complex increased tail flick latency, reduced locomotor activity, and had a dual effect on body temperature. The 30 μg THC/HPβCD formulation only produced a hyperthermic effect. All animals appeared healthy, with no difference between the groups. These results were similar to those obtained in other preclinical studies in which THC was administered centrally using solvents that are unsuitable for IT administration in humans because of their toxicity. Our findings suggest that HPβCD may be a useful carrier for IT administration of THC in humans. Drug Dev Res 78 : 411‐419, 2017. © 2017 Wiley Periodicals, Inc.
The Catalytic Properties of a Copper‐Based Nanoscale Coordination Polymer Fabricated by a Solvent‐Etching Top‐Down Route
Authors: Cao Xiaowei , Fang Zhenlan , Huang Wei , Ju Qiang
Published: September 2017

Manipulating particle size is a powerful means of creating unprecedented applications in both inorganic and organic materials. Coordination polymers, which are emerging as a type of organic–inorganic hybrid materials, have attracted thriving interest in a variety of applications, but nanoscale coordination polymers have scarcely been touched. In this work, the pure‐phase {Cu6[1,4‐bis(imidazol‐1‐yl)butane]3I6}∞ coordination polymer with different sizes and morphologies was synthesized for the first time through a facile top‐down route assisted by solvent etching. The size and morphology could be adjusted simply by varying the participating etching solvents. Our mechanistic investigations suggest that the bulk coordination polymer as a precursor in the etching solvents may experience a process of dispersion, dissolution, and recrystallization to generate the nanoscale counterpart. High catalytic activity of the nanoscale coordination polymer was observed in the N‐arylation of imidazole aryl halides, and this was attributed to a high surface area and a low coordination number of unsaturated coordination sites. This simple and rapid preparation, requiring neither specialized equipment nor harsh conditions, suggests a wealth of potential for reducing the size of coordination polymers to comply with various practical applications.