bluuebunny/crossref_metadata_2025 huggingface dataset:
Ionospheric signatures of gravity waves produced by the 2004 Sumatra and 2011 Tohoku tsunamis: A modeling study
Authors: Yu Yonghui , Wang Wenqing , Hickey Michael P.
Published: December 2016

Ionospheric fluctuations inferred from observations of total electron content have previously been attributed to tsunamis and have confirmed the strong coupling between Earth's ocean and ionosphere via atmospheric gravity waves (AGWs). To further advance our understanding of this wave coupling process we employ a linear full‐wave model and a nonlinear time‐dependent model to examine the ionospheric response to the AGW perturbations induced by the 2004 Sumatra and the 2011 Tohoku tsunamis. In the 2004 case, our modeling analyses reveal that one component of the propagating AGWs becomes dynamically unstable in the E‐region ionosphere at a range exceeding 2000 km in a direction 340° clockwise from north. Another component becomes convectively unstable in the E‐region ionosphere at a range exceeding 700 km in a direction 250° clockwise from north. In the 2011 case, a significant enhancement in the ionospheric disturbance occurs in a direction northwest from the epicenter about 1 h following the tsunami onset, in general agreement with observations. Our simulations also indicate that the AGW propagating toward the southeast is responsible for a traveling ionospheric disturbance that remains of an observable amplitude for over 4 h during which time it propagates horizontally almost 4000 km.
Nonlinear dynamics of electrons interacting with oblique whistler mode chorus in the magnetosphere
Authors: Hsieh Yi‐Kai , Omura Yoshiharu
Published: December 2016

We perform test particle simulations for relativistic electrons interacting with a whistler mode chorus packet propagating at oblique angles. By confirming that the energy transport of oblique lower band chorus is nearly along the ambient magnetic field, we apply the gyroaveraging method in calculating equations of motion of electrons. We trace evolution of a delta function of relativistic electrons in a phase space of kinetic energy and equatorial pitch angle and obtain numerical Green's functions of the chorus wave‐particle interactions. Examining the Green's functions in a wide range of kinetic energies, we find that Landau resonance can accelerate MeV electrons efficiently and that higher nth resonances such as n =− 1 and n = 2 also contribute to acceleration of electrons at high equatorial pitch angles (∼70°) and high energies (∼2 MeV). We investigate the rate of energy gain of the cyclotron resonance acceleration and the Landau resonance acceleration and find that the perpendicular component of wave electric field dominates both accelerations for MeV electrons. Furthermore, the proximity between the parallel components of Vp and Vg of oblique whistler mode waves and the nonlinear trapping condition make the interaction time of Landau resonance much longer than that of n = 1 cyclotron resonance, resulting in efficient acceleration of MeV electrons.
On the governing dynamics of the VHF radar echoes from the mesosphere and collision‐dominated lower E region over Gadanki (13.5°N, 79.2°E)
Authors: Selvaraj D. , Patra A. K. , Sathishkumar S. , Kishore Kumar K. , Narayana Rao D.
Published: December 2016

In the present communication, the role of neutral dynamical processes in governing the morphology and seasonal variations of daytime VHF radar echoes from the mesosphere and the collision‐dominated lower E region is discussed. While the seasonal variations of mesospheric echo occurrence show semiannual variation with their maxima in the equinoxes, the occurrence of E region echoes shows strong annual variation peaking in the summer with two secondary maxima identical to semiannual variation of the mesospheric echoes. The occurrence rates of the E region echoes, however, display year‐to‐year variability. Semiannual variations in the occurrence of low‐latitude mesospheric echoes are closely linked with similar variations in the occurrences of temperature inversion, large wind shear, tides, and gravity wave activities in the same height region. In the case of E region echoes, the summer maximum and equinoctial secondary maxima are found to be linked with similar variations in wind and wind shear, Es activity, tidal, and gravity wave activities. Further, the summer maximum is found to be strongly correlated with that of meteor flux and nonmigrating diurnal tide. This finding is significant given the fact that such wind field in the presence of metallic ions could form both Es and field‐aligned irregularities. The present results show that tides and gravity waves are the most important dynamical factors governing the morphology and seasonal variations of the mesospheric as well as lower E region echoes observed over Gadanki. These results are discussed in the light of current understanding on the dynamical coupling of the mesosphere and lower E region through tides and gravity waves.
Creating space plasma from the ground
Authors: Carlson H. C. , Djuth F. T. , Zhang L. D.
Published: December 2016

We have performed an experiment to compare as directly as realizable the ionization production rate by HF radio wave energy versus by solar EUV. We take advantage of the commonality that ionization production by both ground‐based high‐power HF radio waves and by solar EUV is driven by primary and secondary suprathermal electrons near and above ~20 eV. Incoherent scatter radar (ISR) plasma‐line amplitudes are used as a measure of suprathermal electron fluxes for ISR wavelengths near those for 430 MHz and are indeed a clean measure of such for those fluxes sufficiently weak to have negligible self‐damping. We present data from an HF heating experiment on November 2015 at Arecibo, which even more directly confirm the only prior midlatitude estimate, of order 10% efficiency for conversion of HF energy to ionospheric ionization. We note the theoretical maximum possible is ~1/3, while ~1% or less reduces the question to near practical irrelevance. Our measurements explicitly confirm the prediction that radio‐frequency production of artificial ionospheres can be practicable, even at midlatitudes. Furthermore, that this midlatitude efficiency is comparable to efficiencies measured at high latitudes (which include enhancements unique to high latitudes including magnetic zenith effect, gyrofrequency multiples, and double resonances) requires reexamination of current theoretical thinking about soft‐electron acceleration processes in weakly magnetized plasmas. The implications are that electron acceleration by any of a variety of processes may be a fundamental underpinning to energy redistribution in space plasmas.
Crustal structure and origin of the Eggvin Bank west of Jan Mayen, NE Atlantic
Authors: Tan Pingchuan , Breivik Asbjørn Johan , Trønnes Reidar G. , Mjelde Rolf , Azuma Ryosuke , Eide Sigurd
Published: December 2016

The Eggvin Bank, located between the Jan Mayen Island and Greenland, is an unusually shallow area containing several submarine volcanic peaks, confined by two transforms on the Northern Kolbeinsey Ridge (NKR). We represent P and S wave velocity models for the Eggvin Bank based on an Ocean Bottom Seismometer profile collected in 2011, showing igneous crustal thickness variations from 8 km to 13 km. A 2–5 km increase is associated with two separate 20–30 km wide segments under the main seamounts. The oceanic crust has three layers: upper crust (L2A: 2.8–4.8 km/s), middle crust (L2B: 5.5–6.5 km/s), and lower crust (L3: 6.7–7.35 km/s). Both the thick layer 2(A/B) and the high ratio of layer 2(A/B) thickness to total crustal thickness indicate that secondary, intraplate magmatism built the seamounts of the Eggvin Bank. The seamount in the north where the crust is thickest has a flat top indicating subaerial exposure but is deeper than those with rounded tops in the south and is therefore probably older. Comparing lower crustal seismic velocity with crustal thickness also indicates that the degree of mantle melting may be higher in the north than in the south. An enriched mantle source presently feeds the NKR magmatism and probably influenced the Eggvin Bank development also at earlier times. To what extent the Eggvin Bank has been influenced by the Iceland plume is uncertain, both an enriched mantle component and elevated mantle temperature may have played a role at different times and locations.
Anthropogenic and natural ground deformation in the Hengill geothermal area, Iceland
Authors: Juncu D. , Árnadóttir Th. , Hooper A. , Gunnarsson G.
Published: December 2016

We investigate crustal deformation due to the extraction of water and steam from a high‐enthalpy geothermal reservoir; a common occurrence, yet not well understood. The cause of this deformation can be a change in pressure or in temperature in the reservoir, both of which can be caused by extraction or injection of geothermal fluids. Our study area, the Hengill mountains in SW Iceland, is an active volcanic center and a plate triple junction that hosts two power plants producing geothermal energy. This combination of natural and anthropogenic processes causes a complex displacement field at the surface. We analyze geodetic data—Global Navigation Satellite System and Interferometric Synthetic Aperture Radar—to obtain the surface velocity field, which we then simulate using an inverse modeling approach. We focus on the deformation around the geothermal power plants but need to model the regional tectonic and volcanic deformation as well, because the signals are overlapping. We find that plate motion and a deep contracting body can explain the broad scale signal in the area. Local deformation near the two power plants, Hellisheidi and Nesjavellir, can be explained by extraction of geothermal fluids. We estimate reservoirs extending from 0.6 to 3.0 km depth at Hellisheidi, and 1.0 to 3.0 km depth at Nesjavellir for observed pressure decrease rates of 0.25 MPa/yr and 0.1 MPa/yr, respectively. We find that the main cause for the subsidence in the geothermal area is the observed pressure drawdown.
Links between atmosphere, ocean, and cryosphere from two decades of microseism observations on the Antarctic Peninsula
Authors: Anthony Robert E. , Aster Richard C. , McGrath Daniel
Published: December 2016

The lack of landmasses, climatological low pressure, and strong circumpolar westerly winds between the latitudes of 50°S to 65°S produce exceptional storm‐driven wave conditions in the Southern Ocean. This combination makes the Antarctic Peninsula one of Earth's most notable regions of high‐amplitude wave activity and thus, ocean‐swell‐driven microseism noise in both the primary (direct wave‐coastal region interactions) and secondary (direct ocean floor forcing due to interacting wave trains) period bands. Microseism observations are examined across 23 years (1993–2015) from Palmer Station (PMSA), on the west coast of the Antarctic Peninsula, and from East Falkland Island (EFI). These records provide a spatially integrative measure of both Southern Ocean wave amplitudes and the interactions between ocean waves and the solid Earth in the presence of sea ice, which can reduce wave coupling with the continental shelf. We utilize a spatiotemporal correlation‐based approach to illuminate how the distribution of sea ice influences seasonal microseism power. We characterize primary and secondary microseism power due to variations in sea ice and find that primary microseism energy is both more sensitive to sea ice and more capable of propagating across ocean basins than secondary microseism energy. During positive phases of the Southern Annular Mode, sea ice is reduced in the Bellingshausen Sea and overall storm activity in the Drake Passage increases, thus strongly increasing microseism power levels.
Modeling geomagnetically induced currents
Authors: Boteler D. H. , Pirjola R. J.
Published: December 2016

Understanding the geomagnetic hazard to power systems requires the ability to model the geomagnetically induced currents (GIC) produced in a power network. This paper presents the developments in GIC modeling starting with an examination of fundamental questions about where the driving force for GIC is located. Then we outline the two main network modeling approaches that are mathematically equivalent and show an example for a simple circuit. Accurate modeling of the GIC produced during real space weather events requires including the appropriate system characteristics, magnetic source fields, and Earth conductivity structure. It is shown how multiple voltage levels can be included in GIC modeling and how the network configuration affects the GIC values. Magnetic source fields can be included by using “plane wave” or line current models or by using geomagnetic observatory data with an appropriate interpolation scheme. Earth conductivity structure can be represented by 1‐D, 2‐D, or 3‐D models that are used to calculate the transfer function between electric and magnetic fields at the Earth's surface. For 2‐D and 3‐D structures this will involve a tensor impedance function and electric fields that are not necessarily orthogonal to the magnetic field variations. It is now technically possible to include all these features in the modeling of GIC, and various software implementations are being developed to make these features more accessible for use in risk studies.
Investigation of representing hysteresis in macroscopic models of two‐phase flow in porous media using intermediate scale experimental data
Authors: Cihan Abdullah , Birkholzer Jens , Trevisan Luca , Gonzalez‐Nicolas Ana , Illangasekare Tissa
Published: December 2016

Incorporating hysteresis into models is important to accurately capture the two phase flow behavior when porous media systems undergo cycles of drainage and imbibition such as in the cases of injection and post‐injection redistribution of CO2 during geological CO2 storage (GCS). In the traditional model of two‐phase flow, existing constitutive models that parameterize the hysteresis associated with these processes are generally based on the empirical relationships. This manuscript presents development and testing of mathematical hysteretic capillary pressure—saturation—relative permeability models with the objective of more accurately representing the redistribution of the fluids after injection. The constitutive models are developed by relating macroscopic variables to basic physics of two‐phase capillary displacements at pore‐scale and void space distribution properties. The modeling approach with the developed constitutive models with and without hysteresis as input is tested against some intermediate‐scale flow cell experiments to test the ability of the models to represent movement and capillary trapping of immiscible fluids under macroscopically homogeneous and heterogeneous conditions. The hysteretic two‐phase flow model predicted the overall plume migration and distribution during and post injection reasonably well and represented the postinjection behavior of the plume more accurately than the nonhysteretic models. Based on the results in this study, neglecting hysteresis in the constitutive models of the traditional two‐phase flow theory can seriously overpredict or underpredict the injected fluid distribution during post‐injection under both homogeneous and heterogeneous conditions, depending on the selected value of the residual saturation in the nonhysteretic models.
Serine phosphorylation of the cotton cytosolic pyruvate kinase GhPK6 decreases its stability and activity
Authors: Zhang Bing , Liu Jin‐Yuan
Published: December 2016

Pyruvate kinase (PK, EC 2.7.1.40) is an important glycolytic enzyme involved in multiple physiological and developmental processes. In this study, we demonstrated that cotton cytosolic pyruvate kinase 6 (GhPK6) was phosphorylated at serines 215 and 402. Phosphorylation of GhPK6 at serine 215 inhibited its enzyme activity, whereas phosphorylation at both serine sites could promote its degradation. The phosphorylation‐mediated ubiquitination of GhPK6 was gradually attenuated during the cotton fiber elongation process, which sufficiently explained the increase in the protein/mRNA ratios. These results collectively provided experimental evidence that cotton fiber elongation might be regulated at the post‐translational level.
Human Skin 3D Bioprinting Using Scaffold‐Free Approach
Authors: Pourchet Léa J. , Thepot Amélie , Albouy Marion , Courtial Edwin J. , Boher Aurélie , Blum Loïc J. , Marquette Christophe A.
Published: December 2016

Organ in vitro synthesis is one of the last bottlenecks between tissue engineering and transplantation of synthetic organs. Bioprinting has proven its capacity to produce 3D objects composed of living cells but highly organized tissues such as full thickness skin (dermis + epidermis) are rarely attained. The focus of the present study is to demonstrate the capability of a newly developed ink formulation and the use of an open source printer, for the production of a really complete skin model. Proofs are given through immunostaining and electronic microscopy that the bioprinted skin presents all characteristics of human skin, both at the molecular and macromolecular level. Finally, the printability of large skin objects is demonstrated with the printing of an adult‐size ear.
Double Nanoporous Structure with Nanoporous PtFe Embedded in Graphene Nanopores: Highly Efficient Bifunctional Electrocatalysts for Hydrogen Evolution and Oxygen Reduction
Authors: Zhong Xing , Wang Lei , Zhuang Zhenzhan , Chen Xianlang , Zheng Jian , Zhou Yulin , Zhuang Guilin , Li Xiaonian , Wang Jianguo
Published: December 2016

Pt‐based alloys are considered the universal choice among electrocatalysts for both hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR). However, improving the electrocatalytic efficiency with the use of minimal amount of Pt is very challenging. A new strategy has been developed to fabricate a “double nanoporous” structure, in which nanoporous PtFe alloy (np‐PtFe) is embedded in nanoporous graphene (NPG), through in situ etching and acid leaching treatments. The np‐PtFe/NPG‐700 served as an effective bifunctional catalyst for both HER and ORR, exhibiting higher activity and stability than 20% Pt/C. Theoretical calculations reveal that the graphene nanopores not only play a vital role in improving the stability of the nanoporous PtFe alloy but also downshift the d‐band center of the PtFe alloy, thus improving the catalytic activity. The double nanoporous structure also provides numerous diffusion channels, which facilitated the mass and charge transport during HER and ORR.
A Transition‐Metal‐Free and Base‐Mediated Carbene Insertion into Sulfur‐Sulfur and Selenium‐Selenium Bonds: An Easy Access to Thio‐ and Selenoacetals
Authors: Arunprasath Dhanarajan , Sekar Govindasamy
Published: December 2016

A transition‐metal‐free and base‐mediated carbene insertion across sulfur‐sulfur and selenium‐selenium bonds has been developed by employing N‐tosylhydrazone as a stable and safe carbene precursor. The ylide formation from carbene followed by Stevens rearrangement are considered to be the key steps. This thiol and selenol‐free protocol delivers thioacetals and selenoacetals in good to excellent yields in short reaction time with good functional group tolerance. A one‐pot synthesis involving in situ generation of tosylhydrazone has also been demonstrated.

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Synthesis of Highly Substituted Benzofuran–containing Natural Products via Rh–catalyzed Carbonylative Benzannulation
Authors: Liu Ji‐tian , Simmons Christopher J. , Xie Haibo , Yang Fan , Zhao Xian‐liang , Tang Yu , Tang Weiping
Published: December 2016

We recently developed a novel Rh‐catalyzed carbonylative benzannulation for the synthesis of indoles, benzofurans, and many related heterocycles. In this update, we demonstrated the utility of this method for the synthesis of several highly substituted benzofuran‐containing natural products. The scope and limitation of the Rh‐catalyzed carbonylative benzannulation was investigated in the context of natural product synthesis for the first time. This study also revealed the site‐selectivity for Pd‐catalyzed cross‐coupling of substituted benzofurans. Two one‐pot sequential cross‐couplings were realized based on the observed site‐selectivity. The strategy of preparing bicyclic heterocycles such as benzofurans by de novo synthesis of the benzene ring will find applications in many other related bioactive heterocycles.

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Nanoparticle Functionalization and Its Potentials for Molecular Imaging
Authors: Thiruppathi Rukmani , Mishra Sachin , Ganapathy Mathangi , Padmanabhan Parasuraman , Gulyás Balázs
Published: December 2016

Functionalization enhances the properties and characteristics of nanoparticles through surface modification, and enables them to play a major role in the field of medicine. In molecular imaging, quality functional images are required with proper differentiation which can be seen with high contrast to obtain viable information. This review article discusses how functionalization enhances molecular imaging and enables multimodal imaging by which images with combination of functions particular to each modality can be obtained. This also explains how nanoparticles interacting at molecular level, when functionalized with molecules can target the cells of interest or substances with high specificity, reducing background signal and allowing simultaneous therapies to be carried out while imaging. Functionalization allows imaging for a prolonged period and enables to track the cells over a period of time. Recent researches and progress in functionalizing the nanoparticles to specifically enhance bioimaging with different modalities and their applications are reviewed in this article.
A Chiral Nitrogen Ligand for Enantioselective, Iridium‐Catalyzed Silylation of Aromatic C−H Bonds
Authors: Su Bo , Zhou Tai‐Gang , Li Xian‐Wei , Shao Xiao‐Ru , Xu Pei‐Lin , Wu Wen‐Lian , Hartwig John F. , Shi Zhang‐Jie
Published: December 2016

Iridium catalysts containing dative nitrogen ligands are highly active for the borylation and silylation of C−H bonds, but chiral analogs of these catalysts for enantioselective silylation reactions have not been developed. We report a new chiral pyridinyloxazoline ligand for enantioselective, intramolecular silylation of symmetrical diarylmethoxy diethylsilanes. Regioselective and enantioselective silylation of unsymmetrical substrates was also achieved in the presence of this newly developed system. Preliminary mechanistic studies imply that C−H bond cleavage is irreversible, but not the rate‐determining step.
High‐Throughput Screening of Catalytic H2 Production
Authors: Koo Jamin , Schnabel Tim , Liong Sylvie , Evitt Niklaus H. , Swartz James R.
Published: December 2016

Hydrogenases, ferredoxins, and ferredoxin‐NADP+ reductases (FNR) are redox proteins that mediate electron metabolism in vivo, and are also potential components for biological H2 production technologies. A high‐throughput H2 production assay device (H2PAD) is presented that enables simultaneous evaluation of 96 individual H2 production reactions to identify components that improve performance. Using a CCD camera and image analysis software, H2PAD senses the chemo‐optical response of Pd/WO3 thin films to the H2 produced. H2PAD‐enabled discovery of hydrogenase and FNR mutants that enhance biological H2 production is reported. From a library of 10 080 randomly mutated Clostridium pasteurianum [FeFe] hydrogenases, we found a mutant with nearly 3‐fold higher H2 production specific activity. From a library of 400 semi‐randomly mutated Oryza sativa FNR, the top hit enabled a 60 % increase in NADPH‐driven H2 production rates. H2PAD can also facilitate elucidation of fundamental biochemical mechanisms within these systems.
Die Kristallstruktur von RosB: Einblicke in den Reaktionsmechanismus des ersten Mitglieds einer flavodoxinähnlichen Enzymfamilie
Authors: Konjik Valentino , Brünle Steffen , Demmer Ulrike , Vanselow Amanda , Sandhoff Roger , Ermler Ulrich , Mack Matthias
Published: December 2016

Die 8‐Demethyl‐8‐aminoriboflavin‐5′‐phosphat(AFP)‐Synthase RosB katalysiert die Schlüsselreaktion der Roseoflavinbiosynthese, die Bildung von AFP aus Riboflavin‐5′‐phosphat (RP) und Glutamat. Zwischenprodukte dieser enzymatischen Reaktion sind 8‐Demethyl‐8‐formylriboflavin‐5′‐phosphat (OHC‐RP) und 8‐Demethyl‐8‐carboxylriboflavin‐5′‐phosphat (HO2C‐RP). Um den schwierigen Austausch einer Methylgruppe am Aromaten gegen eine Aminogruppe zu verstehen, haben wir die Struktur von RosB im Komplex mit OHC‐RP (2.0 Å) und im Komplex mit AFP (1.7 Å) gelöst. RosB ist als Homotetramer aktiv und wurde im Verlauf der Evolution mit spezifischen Domänen und einem einzigartigen C‐terminalen Arm ausgestattet. Wir glauben, dass RosB dabei aus einem einfachen Elektronen‐ oder Hydrid‐übertragenden Flavoprotein zu einem komplexen mehrstufigen Enzym “entwickelt” wurde. Im Gegensatz zu anderen Flavoenzymen nutzt RosB RP als Substrat und nicht als Kofaktor. Die strukturelle Analyse des aktiven Zentrums von RosB wurde durch Mutagenesestudien und isotopenbasierte massenspektrometrische Untersuchungen ergänzt. Auf Grundlage dieser Ergebnisse schlagen wir einen Reaktionsmechanismus auf atomarer Ebene vor.
Development of Gold‐catalyzed [4+1] and [2+2+1]/[4+2] Annulations between Propiolate Derivatives and Isoxazoles
Authors: Sahani Rajkumar Lalji , Liu Rai‐Shung
Published: December 2016

Two new gold‐catalyzed annulations of isoxazoles with propiolates have been developed. Most isoxazoles follow an initial O attack on the alkyne to afford a [4+1] annulation product. This process results in a remarkable alkyne cleavage of initial propiolates. Unsubstituted isoxazoles proceed through an N attack step to yield formal [2+2+1]/[4+2] annulation products. These two annulation products arise initially from two seven‐membered heterocyclic intermediates, which then lead to products.
A Stereoconvergent Cyclopropanation Reaction of Styrenes
Authors: del Hoyo Ana M. , Herraiz Ana G. , Suero Marcos G.
Published: December 2016

The first stereoconvergent cyclopropanation reaction by means of photoredox catalysis using diiodomethane as the methylene source is described. This transformation exhibits broad functional group tolerance and it is characterized by an excellent stereocontrol en route to trans‐cyclopropanes regardless of whether E‐ or Z‐styrene substrates were utilized.
Azaindoles as Zinc‐Binding Small‐Molecule Inhibitors of the JAMM Protease CSN5
Authors: Altmann Eva , Erbel Paul , Renatus Martin , Schaefer Michael , Schlierf Anita , Druet Adelaide , Kieffer Laurence , Sorge Mickael , Pfister Keith , Hassiepen Ulrich , Jones Matthew , Ruedisser Simon , Ostermeier Daniela , Martoglio Bruno , Jefferson Anne B. , Quancard Jean
Published: December 2016

CSN5 is the zinc metalloprotease subunit of the COP9 signalosome (CSN), which is an important regulator of cullin‐RING E3 ubiquitin ligases (CRLs). CSN5 is responsible for the cleavage of NEDD8 from CRLs, and blocking deconjugation of NEDD8 traps the CRLs in a hyperactive state, thereby leading to auto‐ubiquitination and ultimately degradation of the substrate recognition subunits. Herein, we describe the discovery of azaindoles as a new class of CSN5 inhibitors, which interact with the active‐site zinc ion of CSN5 through an unprecedented binding mode. The best compounds inhibited CSN5 with nanomolar potency, led to degradation of the substrate recognition subunit Skp2 in cells, and reduced the viability of HCT116 cells.
Nickel‐Catalyzed Barton Decarboxylation and Giese Reactions: A Practical Take on Classic Transforms
Authors: Qin Tian , Malins Lara R. , Edwards Jacob T. , Merchant Rohan R. , Novak Alexander J. E. , Zhong Jacob Z. , Mills Riley B. , Yan Ming , Yuan Changxia , Eastgate Martin D. , Baran Phil S.
Published: December 2016

Two named reactions of fundamental importance and paramount utility in organic synthesis have been reinvestigated, the Barton decarboxylation and Giese radical conjugate addition. N‐hydroxyphthalimide (NHPI) based redox‐active esters were found to be convenient starting materials for simple, thermal, Ni‐catalyzed radical formation and subsequent trapping with either a hydrogen atom source (PhSiH3) or an electron‐deficient olefin. These reactions feature operational simplicity, inexpensive reagents, and enhanced scope as evidenced by examples in the realm of peptide chemistry.
The Crystal Structure of RosB: Insights into the Reaction Mechanism of the First Member of a Family of Flavodoxin‐like Enzymes
Authors: Konjik Valentino , Brünle Steffen , Demmer Ulrike , Vanselow Amanda , Sandhoff Roger , Ermler Ulrich , Mack Matthias
Published: December 2016

8‐demethyl‐8‐aminoriboflavin‐5′‐phosphate (AFP) synthase (RosB) catalyzes the key reaction of roseoflavin biosynthesis by forming AFP from riboflavin‐5′‐phosphate (RP) and glutamate via the intermediates 8‐demethyl‐8‐formylriboflavin‐5′‐phosphate (OHC‐RP) and 8‐demethyl‐8‐carboxylriboflavin‐5′‐phosphate (HO2C‐RP). To understand this reaction in which a methyl substituent of an aromatic ring is replaced by an amine we structurally characterized RosB in complex with OHC‐RP (2.0 Å) and AFP (1.7 Å). RosB is composed of four flavodoxin‐like subunits which have been upgraded with specific extensions and a unique C‐terminal arm. It appears that RosB has evolved from an electron‐ or hydride‐transferring flavoprotein to a sophisticated multi‐step enzyme which uses RP as a substrate (and not as a cofactor). Structure‐based active site analysis was complemented by mutational and isotope‐based mass‐spectrometric data to propose an enzymatic mechanism on an atomic basis.
Skull Anatomy and Ontogeny of Legless Lizard Pseudopus apodus (Pallas, 1775): Heterochronic Influences on Form
Authors: Klembara Jozef , Dobiašová Karolína , Hain Miroslav , Yaryhin Oleksandr
Published: December 2016

Pseudopus apodus (Pallas, 1775) is the largest extant legless species of the subfamily Anguinae (Anguimorpha, Anguidae) living mostly in the sub‐arid territories ranging from the Balkan area in Europe to Kazakhstan in Asia. The species of other two genera live in North America, South‐East Asia and North Africa (Ophisaurus) and Europe and South‐West Asia (Anguis). The interrelationships of Anguinae are unresolved; this is in part the consequence of the insufficient knowledge of the cranial, postcranial and integumentary anatomy of the individual anguine species. The aim of this article is to fulfill this gap in our knowledge of the anguine anatomy. Now, in the first part of the project, the individual bones of the exocranium and visceral endocranium of the anguine legless lizard P. apodus are described in detail. In the present study, P. apodus is revealed to have autoapomorphic features of the skull which clearly distinguish it from Anguis and Ophisaurus. In addition, the study of posthatchling ontogeny of exocranium of P. apodus revealed some features, such as a nasal process of premaxilla being slightly widened in about its mid‐length, that are also typical for adults of the Ophisaurus and Anguis species as well as extinct species of Pseudopus. This strongly indicates that peramorphic heterochronic process played role in the evolution of the P. apodus skull. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:460–502, 2017. © 2016 Wiley Periodicals, Inc.
Synthesis and Docking of Novel 3‐Indolylpropyl Derivatives as New Polypharmacological Agents Displaying Affinity for 5‐HT1AR/SERT
Authors: Pessoa‐Mahana Hernán , Silva‐Matus Paul , Pessoa‐Mahana C. David , Chung Hery , Iturriaga‐Vásquez Patricio , Quiroz Gabriel , Möller‐Acuña Patricia , Zapata‐Torres Gerald , Saitz‐Barría Claudio , Araya‐Maturana Ramiro , Reyes‐Parada Miguel
Published: December 2016

A series of novel 3‐indolylpropyl derivatives was synthesized and evaluated for their binding affinities at the serotonin‐1A receptor subtype (5‐HT1AR) and the 5‐HT transporter (SERT). Compounds 11b and 14b exhibited the highest affinities at the 5‐HT1AR (Ki = 43 and 56 nM), whereas compounds 11c and 14a were the most potent analogs at the SERT (Ki = 34 and 17 nM). On the other hand, compounds 14b and 11d showed potent activity at both targets, displaying a profile that makes them promising leads for the search for novel potent ligands with a dual mechanism of action. Molecular docking studies in all the compounds unveiled relevant drug–target interactions, which allowed rationalizing the observed affinities.
High‐Throughput Synthetic Chemistry Enabled by Organic Solvent Disintegrating Tablet
Authors: Li Tingting , Xu Lei , Xing Yanjun , Xu Bo
Published: December 2016

Synthetic chemistry remains a time‐ and labor‐intensive process of inherent hazardous nature. Our organic solvent disintegrating tablet (O‐Tab) technology has shown potential to make industrial/synthetic chemistry more efficient. As is the case with pharmaceutical tablets, our reagent‐containing O‐Tabs are mechanically strong, but disintegrate rapidly when in contact with reaction media (organic solvents). For O‐Tabs containing sensitive chemicals, they can be further coated to insulate them from air and moisture.
Estimating the prevalence of atrial fibrillation from a three‐class mixture model for repeated diagnoses
Authors: Li Liang , Mao Huzhang , Ishwaran Hemant , Rajeswaran Jeevanantham , Ehrlinger John , Blackstone Eugene H.
Published: December 2016

Atrial fibrillation (AF) is an abnormal heart rhythm characterized by rapid and irregular heartbeat, with or without perceivable symptoms. In clinical practice, the electrocardiogram (ECG) is often used for diagnosis of AF. Since the AF often arrives as recurrent episodes of varying frequency and duration and only the episodes that occur at the time of ECG can be detected, the AF is often underdiagnosed when a limited number of repeated ECGs are used. In studies evaluating the efficacy of AF ablation surgery, each patient undergoes multiple ECGs and the AF status at the time of ECG is recorded. The objective of this paper is to estimate the marginal proportions of patients with or without AF in a population, which are important measures of the efficacy of the treatment. The underdiagnosis problem is addressed by a three‐class mixture regression model in which a patient's probability of having no AF, paroxysmal AF, and permanent AF is modeled by auxiliary baseline covariates in a nested logistic regression. A binomial regression model is specified conditional on a subject being in the paroxysmal AF group. The model parameters are estimated by the Expectation‐Maximization (EM) algorithm. These parameters are themselves nuisance parameters for the purpose of this research, but the estimators of the marginal proportions of interest can be expressed as functions of the data and these nuisance parameters and their variances can be estimated by the sandwich method. We examine the performance of the proposed methodology in simulations and two real data applications.
Identification of lanthanum‐specific peptides for future recycling of rare earth elements from compact fluorescent lamps
Authors: Lederer Franziska L. , Curtis Susan B. , Bachmann Stefanie , Dunbar W.Scott , MacGillivray Ross T.A.
Published: December 2016

As components of electronic scrap, rare earth minerals are an interesting but little used source of raw materials that are highly important for the recycling industry. Currently, there exists no cost‐efficient technology to separate rare earth minerals from an electronic scrap mixture. In this study, phage surface display has been used as a key method to develop peptides with high specificity for particular inorganic targets in electronic scrap. Lanthanum phosphate doped with cerium and terbium as part of the fluorescent phosphors of spent compact fluorescent lamps (CFL) was used as a target material of economic interest to test the suitability of the phage display method to the separation of rare earth minerals. One random pVIII phage library was screened for peptide sequences that bind specifically to the fluorescent phosphor LaPO4:Ce3+,Tb3+ (LAP). The library contained at least 100 binding pVIII peptides per phage particle with a diversity of 1 × 109 different phage per library. After three rounds of enrichment, a phage clone containing the surface peptide loop RCQYPLCS was found to bind specifically to LAP. Specificity and affinity of the identified phage bound peptide was confirmed by using binding and competition assays, immunofluorescence assays, and zeta potential measurements. Binding and immunofluorescence assays identified the peptide's affinity for the fluorescent phosphor components CAT (CeMgAl11O19:Tb3+) and BAM (BaMgAl10O17:Eu2+). No affinity was found for other fluorescent phosphor components such as YOX (Y2O3:Eu3+). The binding specificity of the RCQYPLCS peptide loop was improved 3–51‐fold by using alanine scanning mutagenesis. The identification of peptides with high specificity and affinity for special components in the fluorescent phosphor in CFLs provides a potentially new strategic approach to rare earth recycling. Biotechnol. Bioeng. 2017;114: 1016–1024. © 2016 Wiley Periodicals, Inc.
Bioreactor productivity and media cost comparison for different intensified cell culture processes
Authors: Xu Sen , Gavin John , Jiang Rubin , Chen Hao
Published: December 2016

Process intensification in biomanufacturing has attracted a great deal of interest in recent years. Manufacturing platform improvements leading to higher cell density and bioreactor productivity have been pursued. Here we evaluated a variety of intensified mammalian cell culture processes for producing monoclonal antibodies. Cell culture operational modes including fed‐batch (normal seeding density or high seeding density with N‐1 perfusion), perfusion, and concentrated fed‐batch (CFB) were assessed using the same media set with the same Chinese Hamster Ovary (CHO) cell line. Limited media modification was done to quickly fit the media set to different operational modes. Perfusion and CFB processes were developed using an alternating tangential flow filtration device. Independent of the operational modes, comparable cell specific productivity (fed‐batch: 29.4 pg/cell/day; fed‐batch with N‐1 perfusion: 32.0 pg/cell/day; perfusion: 31.0 pg/cell/day; CFB: 20.1 – 45.1 pg/cell/day) was reached with similar media conditions. Continuous media exchange enabled much higher bioreactor productivity in the perfusion (up to 2.29 g/L/day) and CFB processes (up to 2.04 g/L/day), compared with that in the fed‐batch processes (ranging from 0.39 to 0.49 g/L/day), largely due to the higher cell density maintained. Furthermore, media cost per gram of antibody produced from perfusion was found to be highly comparable with that from fed‐batch; and the media cost for CFB was the highest due to the short batch duration. Our experimental data supports the argument that media cost for perfusion process could be even lower than that in a fed‐batch process, as long as sufficient bioreactor productivity is achieved. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:867–878, 2017
Understand legal remedies for disability‐discrimination claims
Authors: Charmatz Marc
Published: December 2016

The students filing disability‐discrimination claims and the schools facing lawsuits or seeking settlements all want to know: What are the remedies available under Section 504 of the Rehabilitation Act, 29 U.S.C. 794; Title II of the Americans with Disabilities Act, 42 U.S.C. 12131‐65; and Title III of the Americans with Disabilities Act, 42 U.S.C. 12181‐89? It's important to know the substantive law and equally important to know what remedies to expect.
Did a student's allegations defeat motions to dismiss?
Authors: Gelpi Aileen
Published: December 2016

The Medical College of Virginia, Health Sciences Division, of Virginia Commonwealth University admitted Hesham Abbas to medical school. After he completed two years of medical school, Abbas was granted five leaves of absence over a two‐and‐a‐half‐year period for various personal and health reasons.
A New Iridoid Dimer and Other Constituents from the Traditional Kurdish Plant Pterocephalus nestorianus Nábělek
Authors: Abdullah Fuad O. , Hussain Faiq H. S. , Clericuzio Marco , Porta Alessio , Vidari Giovanni
Published: December 2016

Accompanied by other rare compounds, a new iridoid dimer, named kurdnestorianoside (1), showing an unprecedented secologanol configuration, has been isolated for the first time from the Kurdish medicinal plant Pterocephalus nestorianus, which is used in Kurdistan for treating oral diseases and inflammation. The structure of 1 was established from 1D‐ and 2D‐NMR spectroscopic data. Kaempferol 3‐O‐[3,6‐di‐O‐(E)‐p‐coumaroyl]‐β‐d‐glucopyranoside (7) showed a remarkable antiproliferative activity against several human tumor cell lines.
Two New Ergosterol Derivatives from the Basidiomycete Cortinarius glaucopus
Authors: Aung Hnin Thanda , Porta Alessio , Clericuzio Marco , Takaya Yoshiaki , Vidari Giovanni
Published: December 2016

Two new sterols 1 and 2 and five known ones 3 – 7 were isolated for the first time from the fruiting bodies of Cortinarius glaucopus. Their structures were established by 1‐ and 2D‐NMR spectra and HR‐FABS‐MS. The relative configuration of 1 was firmly determined by comparison of the observed 1H–1H couplings and NOESY correlations, with those predicted for the computed geometries of the conformers. Calculations were performed by means of DFT with the B3LYP functional at 6‐31 + G(d,p) level of theory, in CHCl3 as the solvent. The structures of the new ergosterol derivatives, called glaucoposterol A (1) and B (2), were thus established as (3S,5R,7R,10R,13R,17R,20S,22R,23R,24R)‐5,6‐epoxy‐3,7,23‐trihydroxystrophast‐8‐en‐14‐one and (22E,3S,5S,9S,10R,13R,17R,20R,24R)‐3,5‐dihydroxyergosta‐6,8(14),22‐trien‐15‐one, respectively. Moreover, the configuration of known strophasterol C (3) was determined as (3S,5R,6S,7R,10R,13R,17R,20S,22S,24R). Glaucoposterol A (1) and strophasterol C (3) represent the second finding in nature of steroids with the rare strophastane skeleton.
Laserpitium zernyi Hayek Flower and Herb Extracts: Phenolic Compounds, and Anti‐edematous, Antioxidant, and Antimicrobial Activities
Authors: Popović Višnja B. , Tomić Maja A. , Stepanović‐Petrović Radica M. , Micov Ana M. , Milenković Marina T. , Petrović Silvana D. , Ušjak Ljuboš J. , Niketić Marjan S.
Published: December 2016

Phenolic compounds and different biological activities of the dry MeOH extracts of the flowers and the herb (aerial parts without flowers) of Laserpitium zernyi Hayek (Apiaceae) were investigated. The total phenolic contents in the extracts were determined spectrophotometrically using Folin–Ciocalteu reagent. In both extracts, apigenin, luteolin, their 7‐O‐glucosides, and chlorogenic acid were detected by HPLC. Identified phenolics were quantified in both extracts, except luteolin in L. zernyi herb extract. The extracts (p.o.) were tested for anti‐edematous activity in a model of carrageenan (i.pl.) induced rat paw edema. Antioxidant activity of the extracts was assessed by FRAP assay and DPPH and •OH radicals scavenging tests. Antimicrobial activity was investigated using broth microdilution test against five Gram‐positive and three Gram‐negative bacteria, as well as against two strains of Candida albicans. The polyphenol‐richer flower extract exerted higher anti‐edematous and antioxidant activities. The herb extract exhibited better antimicrobial effect against Micrococcus luteus, Enterococcus faecalis, Bacillus subtilis, and Pseudomonas aeruginosa, while against other tested microorganisms, the activity of both extracts was identical. Demonstrated biological activities of L. zernyi flower and herb extracts represent a good basis for their further investigation as potential new herbal medicinal raw materials.
Skin‐derived precursors possess the ability of differentiation into the epidermal progeny and accelerate burn wound healing
Authors: Bayati Vahid , Abbaspour Mohammad Reza , Neisi Niloofar , Hashemitabar Mahmoud
Published: December 2016

Skin‐derived precursors (SKPs) are remnants of the embryonic neural crest stem cells that reside in the dermis until adulthood. Although they possess a wide range of differentiation potentials, their differentiation into keratinocyte‐like cells and their roles in skin wound healing are obscure. The present study aimed to investigate the differentiation of SKPs into keratinocyte‐like cells and evaluate their role in healing of third degree burn wounds. To this aim, SKPs were differentiated into keratinocyte‐like cells on tissue culture plate and collagen–chitosan scaffold prepared by freeze‐drying. Their differentiation capability was detected by real‐time RT‐PCR and immunofluorescence. Thereafter, they were cultured on scaffold and implanted in a rat model of burn wound. Histopathological and immunohistochemical analyses were employed to examine the reconstituted skin. The research findings revealed that SKPs were able to differentiate along the epidermal lineage and this ability can be enhanced on a suitable scaffold. Additionally, the results indicated that SKPs apparently promoted wound healing process and accelerate its transition from proliferating stage to maturational phase, especially if they were differentiated into keratinocyte‐like cells. Regarding the results, it is concluded that SKPs are able to differentiate into keratinocyte‐like cells, particularly when they are cultured on collagen–chitosan scaffold. Moreover, they can regenerate epidermal and dermal layers including thick collagen bundles, possibly through differentiation into keratinocyte‐like cells.
Remarkable Acceleration of Benzimidazole Synthesis and Cyanosilylation Reactions in a Supramolecular Solid Catalyst
Authors: Rojas‐Buzo Sergio , García‐García Pilar , Corma Avelino
Published: December 2016

A solid metal–organic catalyst with hydrophobic pockets and Lewis acid centers strongly accelerates the reaction rate for organic reactions. This is exemplified for the cyanosilylation of ketones and for the synthesis of benzimidazoles, for which very high selectivities are obtained. The solid can be recovered and reused and its behavior approaches that of a functional enzyme mimic.
Selective Catalytic Hydrocarboxylation and Deuterocarboxylation of Allyl Cyanide to Cyanobutanoic Acids with Monodentate and Bidentate Phosphines
Authors: Vallcorba Oriol , Polo Alfonso , Real Julio
Published: December 2016

The hydrocarboxylation of allyl cyanide with monodentate phosphine systems (Pd/triphenylphosphine and protic acid cocatalyst) gave branched 3‐cyano‐2‐methylpropanoic acid chemo‐ and regioselectively, whereas with bidentate systems (Pd/bis[(2‐diphenylphosphino)phenyl] ether and protic acid cocatalyst) it gave linear 4‐cyanobutanoic acid chemo‐ and regioselectively. 3‐Cyano‐2‐methylpropanoic acid and 4‐cyanobutanoic acid were isolated in high yields as carboxylic acids and purified as benzyl esters. No isomerization of allyl cyanide to crotononitrile or its carbonylated derivatives was observed in any case. In parallel experiments, deuterocarboxylation under the same conditions gave the corresponding deuterated products, which were analyzed by MS and 2H NMR spectroscopy: only d0, d1, and d2 products were detected. Deuterium entered the β and γ‐CN positions of the products but never the α position.