bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryptic genetic variation shapes the adaptive evolutionary potential of enzymes
Authors: Baier Florian , Hong Nansook , Yang Gloria , Pabis Anna , Miton Charlotte M , Barrozo Alexandre , Carr Paul D , Kamerlin Shina CL , Jackson Colin J , Tokuriki Nobuhiko
Published: February 2019

Genetic variation among orthologous proteins can cause cryptic phenotypic properties that only manifest in changing environments. Such variation may impact the evolvability of proteins, but the underlying molecular basis remains unclear. Here, we performed comparative directed evolution of four orthologous metallo-β-lactamases toward a new function and found that different starting genotypes evolved to distinct evolutionary outcomes. Despite a low initial fitness, one ortholog reached a significantly higher fitness plateau than its counterparts, via increasing catalytic activity. By contrast, the ortholog with the highest initial activity evolved to a less-optimal and phenotypically distinct outcome through changes in expression, oligomerization and activity. We show how cryptic molecular properties and conformational variation of active site residues in the initial genotypes cause epistasis, that could lead to distinct evolutionary outcomes. Our work highlights the importance of understanding the molecular details that connect genetic variation to protein function to improve the prediction of protein evolution.
Highly Stretchable, High‐Mobility, Free‐Standing All‐Organic Transistors Modulated by Solid‐State Elastomer Electrolytes
Authors: Park Do Hyung , Park Han Wool , Chung Jong Won , Nam Kyungah , Choi Shinyoung , Chung Yoon Sun , Hwang Haejung , Kim BongSoo , Kim Do Hwan
Published: February 2019

Highly stretchable, high‐mobility, and free‐standing coplanar‐type all‐organic transistors based on deformable solid‐state elastomer electrolytes are demonstrated using ionic thermoplastic polyurethane (i‐TPU), thereby showing high reliability under mechanical stimuli as well as low‐voltage operation. Unlike conventional ionic dielectrics, the i‐TPU electrolyte prepared herein has remarkable characteristics, i.e., a large specific capacitance of 5.5 µF cm−2, despite the low weight ratio (20 wt%) of the ionic liquid, high transparency, and even stretchability. These i‐TPU‐based organic transistors exhibit a mobility as high as 7.9 cm2 V−1 s−1, high bendability (Rc, radius of curvature: 7.2 mm), and good stretchability (60% tensile strain). Moreover, they are suitable for low‐voltage operation (VDS = −1.0 V, VGS = −2.5 V). In addition, the electrical characteristics such as mobility, on‐current, and threshold voltage are maintained even in the concave and convex bending state (bending tensile strain of ≈3.4%), respectively. Finally, free‐standing, fully stretchable, and semi‐transparent coplanar‐type all‐organic transistors can be fabricated by introducing a poly(3,4‐ethylenedioxythiophene):polystyrene sulfonic acid layer as source/drain and gate electrodes, thus achieving low‐voltage operation (VDS = −1.5 V, VGS = −2.5 V) and an even higher mobility of up to 17.8 cm2 V−1 s−1. Moreover, these devices withstand stretching up to 80% tensile strain.
Multifunctional Janus Microplates Arrays Actuated by Magnetic Fields for Water/Light Switches and Bio‐Inspired Assimilatory Coloration
Authors: Jiang Shaojun , Hu Yanlei , Wu Hao , Zhang Yachao , Zhang Yiyuan , Wang Yulong , Zhang Yinghui , Zhu Wulin , Li Jiawen , Wu Dong , Chu Jiaru
Published: February 2019

Smart dynamic regulation structured surfaces, inspired by nature, which can dynamically change their surface topographies under external stimuli for convertible fluidic and optical properties, have recently motivated significant interest for scientific research and industrial applications. However, there is still high demand for the development of multifunctional dynamically transformable surfaces using facile preparation strategies. In this work, a type of Janus high‐aspect‐ratio magnetically responsive microplates array (HAR‐MMA) is readily fabricated by integrating a flexible laser scanning strategy, smart shape‐memory‐polymer‐based soft transfer, and a simple surface treatment. By applying external magnetic field, instantaneous and reversible deformation of Janus HAR‐MMA can be actuated, so surface wettability can be reversibly switched between superhydrophobic (158°) and hydrophilic (40°) states, based on which a novel magnetically responsive water droplet switch can be realized. Moreover, inspired by the biological assimilatory coloration of chameleons, dynamically color conversion can be skillfully realized by applying different colors on each side of the Janus HAR‐MMA. Finally, as a proof‐of‐concept demonstration in light manipulation, a HAR‐MMA is applied as an optical shutter actuated by external magnetic field with eximious controllability and repeatability. The developed multifunctional HAR‐MMA provides a versatile platform for microfluidic, biomedical, and optical applications.
Self‐Powered Intracellular Drug Delivery by a Biomechanical Energy‐Driven Triboelectric Nanogenerator
Authors: Liu Zhirong , Nie Jinhui , Miao Bin , Li Jiadong , Cui Yuanbo , Wang Shu , Zhang Xiaodi , Zhao Gengrui , Deng Yongbo , Wu Yihui , Li Zhou , Li Linlin , Wang Zhong Lin
Published: February 2019

Nondestructive, high‐efficiency, and on‐demand intracellular drug/biomacromolecule delivery for therapeutic purposes remains a great challenge. Herein, a biomechanical‐energy‐powered triboelectric nanogenerator (TENG)‐driven electroporation system is developed for intracellular drug delivery with high efficiency and minimal cell damage in vitro and in vivo. In the integrated system, a self‐powered TENG as a stable voltage pulse source triggers the increase of plasma membrane potential and membrane permeability. Cooperatively, the silicon nanoneedle‐array electrode minimizes cellular damage during electroporation via enhancing the localized electrical field at the nanoneedle–cell interface and also decreases plasma membrane fluidity for the enhancement of molecular influx. The integrated system achieves efficient delivery of exogenous materials (small molecules, macromolecules, and siRNA) into different types of cells, including hard‐to‐transfect primary cells, with delivery efficiency up to 90% and cell viability over 94%. Through simple finger friction or hand slapping of the wearable TENGs, it successfully realizes a transdermal biomolecule delivery with an over threefold depth enhancement in mice. This integrated and self‐powered system for active electroporation drug delivery shows great prospect for self‐tuning drug delivery and wearable medicine.
Observation of Crystalline Oxidized Silicon Phase
Authors: Kuzmin Mikhail , Lehtiö Juha‐Pekka , Mäkelä Jaakko , Yasir Muhammad , Rad Zahra Jahanshah , Vuorinen Esa , Lahti Antti , Punkkinen Marko , Laukkanen Pekka , Kokko Kalevi , Hedman Hannu‐Pekka , Punkkinen Risto , Lastusaari Mika , Repo Päivikki , Savin Hele
Published: February 2019

Silica phases, SiOx forming at surfaces of various silicon crystals, e.g., Si wafers, nanowires, and nanoparticles via Si oxidation are key building blocks of diverse applications in the fields of electronics, medicine, and photonics for instance. The Si oxidation has been established to produce amorphous SiOx films, and the resulting oxide/silicon structures are prototypical junctions or contacts of amorphous and crystalline materials of which formation and properties have been extensively studied to understand and develop functionality of SiOx/Si in the applications. Here, observation of hitherto undiscovered phase of the SiOx/Si material, which is crystalline without traditional amorphous silica, is presented. The crystalline SiOx/Si structures are produced in vacuum environment via controlled oxidations of Si where O atoms are incorporated beneath the topmost Si layer. Concomitantly some Si atoms are detached from the crystal, and diffuse to the topmost surface, consistent with previous theoretical predictions, retaining still a pure Si‐surface type reconstruction and leading to a crystalline stack of Si/SiOx/Si. In addition to providing a well‐defined platform to studies of the SiOx/Si system, the found crystalline phase is also hypothesized to decrease amounts of disorder‐induced defects in the applications. Presented electrical characterization via carrier‐lifetime and capacitor measurements support the hypothesis.
Iron‐Catalysed Switchable Synthesis of Pyrrolidines vs Pyrrolidinones by Reductive Amination of Levulinic Acid Derivatives via Hydrosilylation
Authors: Wei Duo , Netkaew Chakkrit , Darcel Christophe
Published: February 2019

A selective production of pyrrolidines vs pyrrolidinones via hydrosilylation of levulinic acid and levulinates by switching of the iron complex catalyst is presented herein. The reactions proceeded efficiently with various anilines and alkylamines under both visible light irradiation and thermal conditions with 43 examples in isolated yields up to 93%. Noticeably, under similar conditions, cyclic amines such as piperidines and azepanes were efficiently synthesized with yields up to 92%, by reaction of anilines with 1,5‐ or 1,6‐keto acids, respectively. Similarly, N‐arylinsolidoline compounds can be prepared from 2‐formylbenzoic acid in 57–93% yields.

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High‐Performance Solution‐Processable Flexible SnSe Nanosheet Films for Lower Grade Waste Heat Recovery
Authors: Rongione Nicolas Augustus , Li Man , Wu Huan , Nguyen Huu Duy , Kang Joon Sang , Ouyang Boya , Xia Hongyan , Hu Yongjie
Published: February 2019

Lower grade waste heat recovery near room temperature is limited due to multiple technology challenges including low efficiency, high cost, and scalability. Here, a low‐cost and scalable solution process is reported to fabricate a nanostructured SnSe thin film, and a high thermoelectric performance near room temperature is demonstrated. This transport study reveals strong phonon scattering near the interfaces between SnSe nanosheets that introduces a large thermal boundary resistance and an ultralow thermal conductivity of 0.09 W m−1 K−1. Moreover, it is demonstrated that the SnSe thin film can be readily implemented on flexible plastic substrates and preserve the high thermoelectric performance over 1000 bending cycles. Together, this study demonstrates a low‐cost and scalable approach to achieve high‐performance flexible thin film energy harvesting devices to power electronics and sensors near room temperature.
Optimizing fluid viscosity for systems of multiple hydraulic fractures
Authors: Cheng Cheng , Bunger Andrew P.
Published: February 2019

Optimal hydraulic fracturing stimulations of horizontal oil and gas wells maximize created fracture surface area and/or maximize the uniformity of stimulation. Here, we use a new, rapidly‐computing hydraulic fracture model to investigate how surface area and uniformity are impacted by interplay among multiple growing hydraulic fractures driven through permeable rocks by fluids of various viscosities. The results show the existence of a surface‐area‐optimizing viscosity that is large enough to control leak‐off but not so large that leads to unnecessarily large fracture aperture.
Sensitivity, specificity, and predictive value of oral mucosal brush biopsy for the diagnosis of peanut allergy
Authors: He Yu Ting , Reisacher William R.
Published: February 2019

Background

Current diagnostic testing methods for peanut allergy, including serum specific immunoglobulin E (sIgE) and skin‐prick testing (SPT), have low specificity, whereas oral food challenge (OFC) carries significant risk of provoking adverse events. Mucosal brush biopsy (MBB) from the oral cavity is currently being studied as a new diagnostic test for peanut allergy, but normative data is not yet available with which to begin measuring specificity and predictive value.

Methods

Twenty individuals with no history of adverse reactions from eating peanuts underwent oral MBB and serum testing for peanut sIgE. These data were then compared with previously published data from 10 individuals with a history of clinical peanut allergy, in order to generate receiver operating characteristic (ROC) curves and calculate the sensitivity, specificity, and positive and negative predictive values for both testing modalities.

Results

The optimal cutoff levels for oral MBB and sIgE testing were 0.12 kU/L and 1.0 kU/L, respectively. At 0.12 kU/L, the sensitivity of oral MBB testing was 80% and the specificity was 85%, whereas at 1.0 kU/L, the sensitivity of sIgE testing was 50% and the specificity was 100%. From the ROC curves, the areas under the ROC curve (AUC) for oral MBB and sIgE were 0.91 (p < 0.001) and 0.74 (p = 0.007), respectively. Combination testing further increased both sensitivity and accuracy over oral MBB alone.

Conclusion

In this pilot study, oral MBB demonstrated high sensitivity and specificity for screening individuals with and without oral cavity clinical reactivity to peanuts and may represent a potentially useful testing method for the diagnosis of peanut allergy in the future.
Emerging Palladium and Nickel Catalysts for Copolymerization of Olefins with Polar Monomers
Authors: Tan Chen , Chen Changle
Published: February 2019

Transition‐metal‐catalyzed copolymerization of olefins with polar monomers represents a challenge because of the large variety of substrate‐induced side reactions. However, this approach also holds the potential for the direct synthesis of polar functionalized polyolefins with unique properties. After decades of research, only a few catalyst systems have been found to be suitable for this reaction. Some major advances in catalyst development have been made in the past five years. This Minireview summarizes some of the recent progress in the extensively studied Brookhart and Drent catalyst systems, as well as emerging alternative palladium and nickel catalysts.
CoP‐Doped MOF‐Based Electrocatalyst for pH‐Universal Hydrogen Evolution Reaction
Authors: Liu Teng , Li Peng , Yao Na , Cheng Gongzhen , Chen Shengli , Luo Wei , Yin Yadong
Published: February 2019

Although electrocatalysts based on transition metal phosphides (TMPs) with cationic/anionic doping have been widely studied for hydrogen evolution reaction (HER), the origin of performance enhancement still remains elusive mainly due to the random dispersion of dopants. Herein, we report a controllable partial phosphorization strategy to generate CoP species within the Co‐based metal‐organic framework (Co‐MOF). Density functional theory calculations and experimental results reveal that the electron transfer from CoP to Co‐MOF through N‐P/N‐Co bonds could lead to the optimized adsorption energy of H2O (ΔG
) and hydrogen (ΔGH*), which, together with the unique porous structure of Co‐MOF, contributes to the remarkable HER performance with an overpotential of 49 mV at a current density of 10 mA cm−2 in 1 m phosphate buffer solution (PBS, pH 7.0). The excellent catalytic performance exceeds almost all the documented TMP‐based and non‐noble‐metal‐based electrocatalysts. In addition, the CoP/Co‐MOF hybrid also displays Pt‐like performance in 0.5 m H2SO4 and 1 m KOH, with the overpotentials of 27 and 34 mV, respectively, at a current density of 10 mA cm−2.
Development of microsatellite markers for a monotypic and globally endangered species, Glyptostrobus pensilis (Cupressaceae)
Authors: Wang Gang‐Tao , Wang Zheng‐Feng , Wang Rui‐Jiang , Liang Dan , Jiang Guo‐Bin
Published: February 2019

Premise of the Study

Microsatellite markers were developed to facilitate studies of genetic diversity and structure in Glyptostrobus pensilis, a critically endangered and monotypic conifer species.

Methods and Results

Using restriction site–associated DNA sequencing (RAD‐Seq), we developed 10 polymorphic and 27 monomorphic microsatellite markers. Polymorphism was characterized using 333 individuals from nine populations. The number of alleles per locus ranged from one to 14 at the population level. The levels of observed and unbiased expected heterozygosities varied from 0.058 to 0.844 and 0.219 to 0.583, respectively. Nine of these 10 polymorphic markers were successfully cross‐amplified in Taxodium distichum, the species most closely related to G. pensilis.

Conclusions

These microsatellite markers can be used to reveal the genetic diversity in existing populations of G. pensilis, enabling its conservation and restoration.
Ring Size Effects on Multi‐Stimuli Responsive Luminescent Properties of Cyclic Amine Substituted β‐Diketones and Difluoroboron Complexes
Authors: Wang Fang , Song Daniel , Dickie Diane A. , Fraser Cassandra L.
Published: February 2019

Emissive β‐diketones (bdks) and difluoroboron complexes (BF2bdks) show multi‐stimuli responsive luminescence in both solution and the solid state. A series of bdk ligands and boron coordinated dyes were synthesized with different cyclic amine substituents in the 4‐position to explore ring size effects on various luminescent properties, including solvatochromism, viscochromism, aggregation‐induced emission (AIE), mechanochromic luminescence (ML) and halochromism. Red‐shifted absorption and emission were observed in CH2Cl2 for both bdk ligands and boron dyes with increasing substituent ring size. The compounds displayed bathochromic emission in more polar solvents, and higher fluorescence intensity in more viscous media. The AIE compounds exhibited enhanced emission when aggregated. For solid‐state properties, a large emission wavelength shift was shown for the piperidine substituted bdk after melt quenching on weighing paper. Large blue‐shifted emissions were observed in all the boron dye spin cast films after trifluoroacetic acid vapor annealing, and the original emissions were partially recovered after triethylamine vapor treatment.
Predicting the Outcome of Photocyclisation Reactions: A Joint Experimental and Computational Investigation
Authors: Wonanke A. D. Dinga , Ferguson Jayne L. , Fitchett Christopher M. , Crittenden Deborah L.
Published: February 2019

Photochemical oxidative cyclodehydrogenation reactions are a versatile class of aromatic ring‐forming reactions. They are tolerant to functional group substitution and heteroatom inclusion, so can be used to form a diverse range of extended polyaromatic systems by fusing existing ring substituents. However, despite their undoubted synthetic utility, there are no existing models—computational or heuristic—that predict the outcome of photocyclisation reactions across all possible classes of reactants. This can be traced back to the fact that “negative” results are rarely published in the synthetic literature and the lack of a general conceptual framework for understanding how photoexcitation affects reactivity. In this work, we address both of these issues. We present experimental data for a series of aromatically substituted pyrroles and indoles, and show that quantifying induced atomic forces upon photoexcitation provides a powerful predictive model for determining whether a given reactant will photoplanarise and hence proceed to photocyclised product under appropriate reaction conditions. The propensity of a molecule to photoplanarise is related to localised changes in charge distribution around the putative forming ring upon photoexcitation. This is promoted by asymmetry in molecular structures and/or charge distributions, inclusion of heteroatoms and ethylene bridging and well‐separated or isolated photocyclisation sites.
Relation between adaptive function and IQ among youth with histories of heavy prenatal alcohol exposure
Authors: Doyle Lauren R. , Coles Claire D. , Kable Julie A. , May Philip A. , Sowell Elizabeth R. , Jones Kenneth L. , Riley Edward P. , Mattson Sarah N. ,   the CIFASD
Published: February 2019

Background

Adaptive function and general intellectual function are two important and often correlated domains. While youth with prenatal alcohol exposure frequently demonstrate impairments in both domains, it is not clear whether the relation between these domains is consistent across levels of ability or whether, for example, adaptive function is less affected by intellectual function at higher ability levels. The aim of the current study was to test this relation in youth with and without prenatal alcohol exposure.

Methods

As part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, Phase II, subjects with heavy prenatal alcohol exposure (AE) and nonexposed subjects with and without other clinical conditions or concerns (CON) completed a comprehensive neurobehavioral battery. Multiple regression analyses tested the relation between full scale IQ (FSIQ) and overall adaptive function. Interaction terms between Group and each variable were created to formally test for group differences. Three subsequent regression analyses tested which adaptive function domains (Communication, Daily Living Skills, Socialization) significantly contributed to results. Follow‐up analyses examined correlations based on IQ range (low IQ <85; high IQ ≥85).

Results

The interaction between FSIQ and Group on overall adaptive function was significant; the relationship between FSIQ and adaptive function was weaker in the AE group than in the CON group. Regarding specific adaptive function domains, the interaction between FSIQ and Group was significant only in the Communication domain. Follow‐up analyses showed, within the low IQ range, the correlation between FSIQ and Communication was stronger in the CON group than the AE group. Within the high IQ range, the correlation between FSIQ and Communication was significant only in the CON group.

Conclusions

Although higher intellectual functioning was associated with better adaptive function ability among controls, this was not found among the alcohol‐exposed youth where a general dampening of adaptive ability was noted. Further, the differential relationship between IQ and adaptive function between groups appears to be driven by communication abilities. These findings suggest that level of intellectual functioning of children with prenatal alcohol exposure does not fully account for caregiver‐reported communication and overall adaptive function deficits particularly at higher levels of functioning.
Testing random effects in linear mixed‐effects models with serially correlated errors
Authors: Drikvandi Reza , Noorian Sajad
Published: February 2019

In linear mixed‐effects models, random effects are used to capture the heterogeneity and variability between individuals due to unmeasured covariates or unknown biological differences. Testing for the need of random effects is a nonstandard problem because it requires testing on the boundary of parameter space where the asymptotic chi‐squared distribution of the classical tests such as likelihood ratio and score tests is incorrect. In the literature several tests have been proposed to overcome this difficulty, however all of these tests rely on the restrictive assumption of i.i.d. measurement errors. The presence of correlated errors, which often happens in practice, makes testing random effects much more difficult. In this paper, we propose a permutation test for random effects in the presence of serially correlated errors. The proposed test not only avoids issues with the boundary of parameter space, but also can be used for testing multiple random effects and any subset of them. Our permutation procedure includes the permutation procedure in Drikvandi, Verbeke, Khodadadi, and Partovi Nia (2013) as a special case when errors are i.i.d., though the test statistics are different. We use simulations and a real data analysis to evaluate the performance of the proposed permutation test. We have found that random slopes for linear and quadratic time effects may not be significant when measurement errors are serially correlated.
Wählerisch für den Nachwuchs
Authors: Irsch Wilhelm
Published: February 2019

Bei der Auswahl des Nistmaterials erweisen sich Meisen als fürsorgliche Eltern.
Nostoc flagelliforme – ein Bakterium unter Naturschutz
Authors: Engelhardt Harald
Published: February 2019

Steppengebiete der Inneren Mongolei degenerien seit Jahrzehnten zur Wüste und verstärken verheerende Sandstürme im Norden Chinas. Gründe dafür sind Überweidung, die damit einhergehende Zerstörung der Bodenkruste und das massive Absammeln des Stickstoff fixierenden Cyanobakteriums Nostoc flagelliforme. Das schwer kultivierbare, fädige Bakterium hatte sich zum begehrten Genussmittel entwickelt und fehlte bald für Düngung und Regenerierung des Bodens, bis wildes Ernten von Nostoc und der Handel damit verboten wurden.
Kann das nicht der Computer machen? Warum Biologen die Programmiersprache Python lernen sollten
Authors: Rauch Christian
Published: February 2019

Es ist kein Geheimnis: Ob Genomics, Proteomics oder Metabolomics, die Biologie kommt im Zeitalter der Omics nicht mehr ohne ihre Schwesterwissenschaft Bioinformatik aus. Was aus dem Labor heraus manchmal wie moderne Zauberei erscheint, birgt erstaunliche Verbesserungen für den wissenschaftlichen Alltag. Es braucht nur ein wenig Abenteuerlust.
Die Bescheidenheitsfalle
Authors: Hauk Andrea
Published: February 2019

Es wird viel diskutiert über die Vereinbarkeit von Familie und Beruf. Andrea Hauk – BIUZ‐Lesern bekannt als Autorin der Laborseite – hat den Praxistest gemacht und berichtet nun im dreizehnten Teil unserer Reihe von ihren Erfahrungen als Mutter eines Kleinkindes.
Synthesis and Biological Activity of Some Benzochromenoquinolinones: Tacrine Analogs as Potent Anti‐Alzheimer's Agents
Authors: Mahdavi Mohammad , Hariri Roshanak , Mirfazli Seyedeh Sara , Lotfian Hania , Rastergari Arezoo , Firuzi Omidreza , Edraki Najmeh , Larijani Bagher , Akbarzadeh Tahmineh , Saeedi Mina
Published: February 2019

Alzheimer's disease (AD) is a well‐known neurodegenerative disorder affecting millions of old people worldwide and the corresponding epidemiological data emphasize the importance of the disease. As AD is a multifactorial illness, various single target directed drugs that have reached clinical trials have failed. Therefore, various factors associated with outset of AD have been considered in targeted drug discovery. In this work, various benzochromenoquinolinones were synthesized and evaluated for their cholinesterase and BACE1 inhibitory activities as well as neuroprotective and metal‐chelating properties. Among the synthesized compounds, 14‐amino‐13‐(3‐nitrophenyl)‐2,3,4,13‐tetrahydro‐1H‐benzo[6,7]chromeno[2,3‐b]quinoline‐7,12‐dione (6m) depicted the best inhibitory activity toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50s of 0.86 and 6.03 μm, respectively. Also, the compound could inhibit β‐secretase 1 (BACE1) with IC50=19.60 μm and showed metal chelating ability toward Cu2+, Fe2+, and Zn2+. In addition, docking study demonstrated desirable interactions of compound 6m with amino acid residues characterizing AChE, BChE, and BACE1.
A new Sherriff in town: Vascular calcium meets its match
Authors: Auberson Denise , Gray William A.
Published: February 2019

Key Points

Severe vascular calcification in femoropopliteal disease is associated with worse short‐ and long‐term outcomes.

Intravascular lithotripsy therapy causes micro‐fractures in intimal and medial calcium at low‐pressure inflations. This results acute luminal gain, with minimal vessel injury in calcified lesions.

Ongoing trials will determine the benefit of intravascular lithotripsy as an adjunct to drug coated balloons in peripheral vascular disease.
Great report, food for thought, or wait a second?
Authors: Butman Samuel
Published: February 2019

Key Points

In this retrospective report, earlier intervention in NSTEMI reduced the composite outcome and mortality at 1 year.

However, earlier intervention did not significantly reduce the composite outcome or mortality at 30 days.

Reminder: retrospective (even propensity‐matched) trials may suggest differences that prospective randomized trials may or may not support
Hybrid 2.0: Subintimal plaque modification for facilitation of future success in chronic total occlusion percutaneous coronary intervention
Authors: Hall Allison B. , Brilakis Emmanouil S.
Published: February 2019

Key Points

The Subintimal Tracking and Reentry (STAR) technique is not suitable for routine use during chronic total occlusion percutaneous coronary intervention due to side branch loss and long stent length, leading to high restenosis and re‐occlusion rates.

STAR without stenting (also called subintimal plaque modification [SPM]) can be used as a bailout strategy in CTO PCI, when standard crossing attempts fail. Repeat angiography is performed 2–4 months later, often showing lumen reconstitution and dissection healing, at which time the intervention can be successfully completed in many cases.

Subintimal plaque modification may become an important element of the expanded hybrid algorithm. Four parameters are constantly being evaluated during the procedure: radiation dose, contrast volume, procedure time and risk of the remaining treatment options, to determine if the procedure needs to stop. Before stopping, SPM may be used to facilitate future success.
Design and Structural Evolution of Matrix Metalloproteinase Inhibitors
Authors: Fischer Thomas , Senn Nicole , Riedl Rainer
Published: February 2019

Matrix metalloproteinases (MMPs) are involved in a multitude of severe diseases. Despite MMPs being considered druggable targets, past drug‐discovery programs have not delivered the anticipated clinical benefits. This review examines the latest structural evolution of small‐molecule inhibitors of MMPs, with a focus on the development of novel chemical entities with improved affinity and selectivity profiles. X‐ray crystallographic data of the protein targets and cocrystal structures with inhibitors proved to be key for the success achieved during this ambitious endeavor. An evolutionary view on the structural diversity generated for this class of molecules is provided. This encouraging development paves the way for the clinical utilization of this class of highly relevant therapeutic targets. The structure‐based design of superior MMP inhibitors highlights the power of this technique and displays strategies for the development of treatment options based on the modulation of challenging drug targets.
Origin of Selectivity of a Triazinyl Ligand for Americium(III) over Neodymium(III)
Authors: Dan David , Celis‐Barros Cristian , White Frankie D. , Sperling Joseph M. , Albrecht‐Schmitt Thomas E.
Published: February 2019

[M(EtBTP)3][BPh4]3⋅3 CH3CN (M=Nd, Am; EtBTP=2,6‐bis(5,6‐diethyl‐1,2,4‐triazin‐3‐yl)pyridine) have been synthesized from reactions of MCl3⋅n H2O with EtBTP in acetonitrile followed by anion metathesis. Structural analysis reveals that these compounds contain M3+cations bound by tridentate EtBTP ligands to create a tricapped trigonal prismatic geometry around the metal centers. Collection of high‐resolution, single‐crystal X‐ray diffraction data also allowed reduction in bond lengths esd's, such that a slight contraction of Δ=0.0158(18) Å in the Am−N versus Nd−N bond lengths was observed, even though these cations ostensibly have matching ionic radii. Theoretical evaluation revealed enhanced metal–ligand bonding through back donation in the [Am(EtBTP)3]3+complex that is absent in [Nd(EtBTP)3]3+.
Tuning the Selectivity of AuPd Nanoalloys towards Selective Dehydrogenative Alkyne Silylation
Authors: Wissing Maren , Studer Armido
Published: February 2019

The cross‐dehydrogenative coupling of terminal alkynes and hydrosilanes catalyzed by AuPd nanoalloys is described. Metal nanoparticles are readily prepared in 15 minutes from commercially available and cheap starting materials by using a photochemical approach. The ratio of Au and Pd in the alloys heavily influences their reactivity. These cooperative nanoalloy catalysts tolerate a large number of functional groups (e.g., free amines and acids), operate at room temperature under air atmosphere at low loading (2 mol %), and the cross‐dehydrogenative coupling can easily be scaled up.
A rule‐based method to model myocardial fiber orientation in cardiac biventricular geometries with outflow tracts
Authors: Doste Ruben , Soto‐Iglesias David , Bernardino Gabriel , Alcaine Alejandro , Sebastian Rafael , Giffard‐Roisin Sophie , Sermesant Maxime , Berruezo Antonio , Sanchez‐Quintana Damian , Camara Oscar
Published: February 2019

Rule‐based methods are often used for assigning fiber orientation to cardiac anatomical models. However, existing methods have been developed using data mostly from the left ventricle. As a consequence, fiber information obtained from rule‐based methods often does not match histological data in other areas of the heart such as the right ventricle, having a negative impact in cardiac simulations beyond the left ventricle. In this work, we present a rule‐based method where fiber orientation is separately modeled in each ventricle following observations from histology. This allows to create detailed fiber orientation in specific regions such as the endocardium of the right ventricle, the interventricular septum, and the outflow tracts. We also carried out electrophysiological simulations involving these structures and with different fiber configurations. In particular, we built a modeling pipeline for creating patient‐specific volumetric meshes of biventricular geometries, including the outflow tracts, and subsequently simulate the electrical wavefront propagation in outflow tract ventricular arrhythmias with different origins for the ectopic focus. The resulting simulations with the proposed rule‐based method showed a very good agreement with clinical parameters such as the 10 ms isochrone ratio in a cohort of nine patients suffering from this type of arrhythmia. The developed modeling pipeline confirms its potential for an in silico identification of the site of origin in outflow tract ventricular arrhythmias before clinical intervention.
Traffic modeling and performance evaluation of SDN‐based NB‐IoT access network
Authors: Chen Xin , Li Zhuo , Chen Ying , Du Bing , Zhang Yongchao
Published: February 2019

Narrow Band Internet of Things (NB‐IoT) is a cellular‐based low power wide area network (LPWAN) radio technology, which can provide highly reliable services and wide coverage for IoT devices. Software defined networking (SDN) as an emerging network architecture can realize flexible resource allocation and network management. We introduce SDN into NB‐IoT and investigate the traffic modeling and performance evaluation of SDN‐based NB‐IoT access network. To evaluate the network performance in different environments, we introduce the Beta/D/1, Uniform/D/1, and M/D/1 queuing models, respectively. The proposed queuing models are suitable for different scenarios, in which NB‐IoT devices access the network in a highly synchronized, unsynchronized, or stochastic manner. We use the general solution to the G/G/1 and the M/G/1 queuing model to solve the proposed modeling problems. Through simulations, we investigate the influence of different network parameters. The analysis and simulation results can be used in the SDN controller to dynamically allocate resources and make network management decisions to satisfy different performance requirements of NB‐IoT applications.
Exploring Ternary and Quaternary Mixtures in the LiBH4‐NaBH4‐KBH4‐Mg(BH4)2‐Ca(BH4)2 System
Authors: Dematteis Erika M. , Pistidda Claudio , Dornheim Martin , Baricco Marcello
Published: February 2019

Binary combinations of borohydrides have been extensivly investigated evidencing the formation of eutectics, bimetallic compounds or solid solutions. In this paper, the investigation has been extended to ternary and quaternary systems in the LiBH4‐NaBH4‐KBH4‐Mg(BH4)2‐Ca(BH4)2 system. Possible interactions among borohydrides in equimolar composition has been explored by mechanochemical treatment. The obtained phases were analysed by X‐ray diffraction and the thermal behaviour of the mixtures were analysed by HP‐DSC and DTA, defining temperature of transitions and decomposition reactions. The release of hydrogen was detected by MS, showing the role of the presence of solid solutions and multi‐cation compounds on the hydrogen desorption reactions. The presence of LiBH4 generally promotes the release of H2 at about 200 °C, while KCa(BH4)3 promotes the release in a single‐step reaction at higher temperatures.
Artificial Restriction DNA Cutter Using Nuclease S1 for Site‐Selective Scission of Genomic DNA
Authors: Rajendran Arivazhagan , Shigi Narumi , Sumaoka Jun , Komiyama Makoto
Published: February 2019

By combining a pair of pseudo‐complementary peptide nucleic acids (pcPNAs) with S1 nuclease, a novel tool to cut DNA at a predetermined site can be obtained. Complementary pcPNAs invade the DNA duplex and base pair to each strand of a target site, creating single‐stranded regions that are cleaved by S1 nuclease. The scission site can be freely modulated by the design of pcPNAs. This method can be used to cleave a single site in the human genome. This protocol presents experimental details for site‐selective scission using this versatile new tool. © 2019 by John Wiley & Sons, Inc.
Isolation of Neural Stem Cells from Whole Brain Tissues of Adult Mice
Authors: Deshpande Krutika , Saatian Behnaz , Martirosian Vahan , Lin Michelle , Julian Alex , Neman Josh
Published: February 2019

A population of neural stem cells exists in the adult mammalian central nervous system. Purification and characterization of neurospheres provide valuable tools to study the regulation and differentiation of neural stem cells both in vitro and in vivo. Successful stimulation and production of neurospheres can ultimately be used for therapeutic purposes. The currently available methods are limited by their poor yield and the large number of animals required to compensate for that. Here, we describe a procedure to purify neurospheres from adult mouse whole brain. We provide detailed steps on how to propagate, passage, and maintain the adult neurospheres, and how to differentiate the pure neurospheres into the lineage of interest. Using this method, neurospheres can be easily derived from adult mouse whole brain. The derived adult neurospheres maintain their homogenous undifferentiated status while retaining their differentiation potential. This new protocol facilitates adult neurospheres isolation, purification, maintenance, and differentiation. © 2019 by John Wiley & Sons, Inc.
A dynamic multi‐scale occupancy model to estimate temporal dynamics and hierarchical habitat use for nomadic species
Authors: Green Adam W. , Pavlacky David C. , George T. Luke
Published: February 2019

Distribution models are increasingly being used to understand how landscape and climatic changes are affecting the processes driving spatial and temporal distributions of plants and animals. However, many modeling efforts ignore the dynamic processes that drive distributional patterns at different scales, which may result in misleading inference about the factors influencing species distributions. Current occupancy models allow estimation of occupancy at different scales and, separately, estimation of immigration and emigration. However, joint estimation of local extinction, colonization, and occupancy within a multi‐scale model is currently unpublished. We extended multi‐scale models to account for the dynamic processes governing species distributions, while concurrently modeling local‐scale availability. We fit the model to data for lark buntings and chestnut‐collared longspurs in the Great Plains, USA, collected under the Integrated Monitoring in Bird Conservation Regions program. We investigate how the amount of grassland and shrubland and annual vegetation conditions affect bird occupancy dynamics and local vegetation structure affects fine‐scale occupancy. Buntings were prevalent and longspurs rare in our study area, but both species were locally prevalent when present. Buntings colonized sites with preferred habitat configurations, longspurs colonized a wider range of landscape conditions, and site persistence of both was higher at sites with greener vegetation. Turnover rates were high for both species, quantifying the nomadic behavior of the species. Our model allows researchers to jointly investigate temporal dynamics of species distributions and hierarchical habitat use. Our results indicate that grassland birds respond to different covariates at landscape and local scales suggesting different conservation goals at each scale. High turnover rates of these species highlight the need to account for the dynamics of nomadic species, and our model can help inform how to coordinate management efforts to provide appropriate habitat configurations at the landscape scale and provide habitat targets for local managers.
Animal movement tools (amt): R package for managing tracking data and conducting habitat selection analyses
Authors: Signer Johannes , Fieberg John , Avgar Tal
Published: February 2019

Advances in tracking technology have led to an exponential increase in animal location data, greatly enhancing our ability to address interesting questions in movement ecology, but also presenting new challenges related to data management and analysis. Step‐selection functions (SSFs) are commonly used to link environmental covariates to animal location data collected at fine temporal resolution. SSFs are estimated by comparing observed steps connecting successive animal locations to random steps, using a likelihood equivalent of a Cox proportional hazards model. By using common statistical distributions to model step length and turn angle distributions, and including habitat‐ and movement‐related covariates (functions of distances between points, angular deviations), it is possible to make inference regarding habitat selection and movement processes or to control one process while investigating the other. The fitted model can also be used to estimate utilization distributions and mechanistic home ranges. Here, we present the R package amt (animal movement tools) that allows users to fit SSFs to data and to simulate space use of animals from fitted models. The amt package also provides tools for managing telemetry data. Using fisher (Pekania pennanti) data as a case study, we illustrate a four‐step approach to the analysis of animal movement data, consisting of data management, exploratory data analysis, fitting of models, and simulating from fitted models.
Estimability of migration survival rates from integrated breeding and winter capture–recapture data
Authors: Rushing Clark S.
Published: February 2019

Long‐distance migration is a common phenomenon across the animal kingdom but the scale of annual migratory movements has made it difficult for researchers to estimate survival rates during these periods of the annual cycle. Estimating migration survival is particularly challenging for small‐bodied species that cannot carry satellite tags, a group that includes the vast majority of migratory species. When capture–recapture data are available for linked breeding and non‐breeding populations, estimation of overall migration survival is possible but current methods do not allow separate estimation of spring and autumn survival rates. Recent development of a Bayesian integrated survival model has provided a method to separately estimate the latent spring and autumn survival rates using capture–recapture data, though the accuracy and precision of these estimates has not been formally tested. Here, I used simulated data to explore the estimability of migration survival rates using this model. Under a variety of biologically realistic scenarios, I demonstrate that spring and autumn migration survival can be estimated from the integrated survival model, though estimates are biased toward the overall migration survival probability. The direction and magnitude of this bias are influenced by the relative difference in spring and autumn survival rates as well as the degree of annual variation in these rates. The inclusion of covariates can improve the model's performance, especially when annual variation in migration survival rates is low. Migration survival rates can be estimated from relatively short time series (4–5 years), but bias and precision of estimates are improved when longer time series (10–12 years) are available. The ability to estimate seasonal survival rates of small, migratory organisms opens the door to advancing our understanding of the ecology and conservation of these species. Application of this method will enable researchers to better understand when mortality occurs across the annual cycle and how the migratory periods contribute to population dynamics. Integrating summer and winter capture data requires knowledge of the migratory connectivity of sampled populations and therefore efforts to simultaneously collect both survival and tracking data should be a high priority, especially for species of conservation concern.
A New Secondary Metabolite from Alternaria Alternata: Structure Elucidation and Total Synthesis of Altenuic Acid IV
Authors: Kohler Dominik , Podlech Joachim
Published: February 2019

A putative intermediate in the biosynthesis of altenuic acids I–III was isolated from Alternaria alternata in the 1950ies and a sample survived over the decades. This resorcylic lactone named altenuic acid IV is a composite of a resorcylic and a muconic acid. Its structure was confirmed by NMR spectroscopy and by total synthesis. Altenuic acid IV was here obtained starting with 2‐bromo‐4,6‐dimethoxybenzene and 4‐methylbenzene‐1,2‐diol with a total yield of 20 %. The synthesis was achieved in ten steps where the longest sequence consists of seven steps. Key steps were an oxidative ring opening of a bromocresol furnishing a bromomuconate and its Suzuki coupling with a resorcylate‐derived boronate.
Nafion‐modified Carbon Based Sensor for Soil Potassium Detection
Authors: Bhandari Shruti , Singh Urvasini , Kumbhat Sunita
Published: February 2019

In the present investigation, we report a voltammetric sensor based on Nafion modified screen printed carbon ink functionalized with 4‐aminobenzo‐18‐crown‐6 ether for the detection of soil potassium. The potassium is one of the major nutrient elements required by the plants and is critical for the crop productivity. The selective and sensitive assay is based on recording change in current signal of a positively charged redox probe, hexammineruthenium(III)chloride in the absence and presence of K+ ion in solution. The sensing interface is highly stable and reproducible for detection of K+ ion a under a wide range of concentration 1 to 500 ppm. The detection sensitivity over a wide concentration range was achieved by altering the concentration of redox species. Mechanistically, the recognition properties of 4‐aminobenzo‐18‐Crown‐6 covalently bound to the Nafion on carbon surface was found to be selective for potassium ion over sodium, ammonium and calcium ion. Potassium recognition through host‐guest binding of crown ether derivative and proposed simplicity of fabrication protocol makes the systems highly promising for real‐time applications in soil analysis.