bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemoenzymatische Totalsynthese von Deoxy‐, epi‐ und Podophyllotoxin sowie biokatalytische kinetische Racematspaltung von Dibenzylbutyrolactonen
Authors: Lazzarotto Mattia , Hammerer Lucas , Hetmann Michael , Borg Annika , Schmermund Luca , Steiner Lorenz , Hartmann Peter , Belaj Ferdinand , Kroutil Wolfgang , Gruber Karl , Fuchs Michael
Published: March 2019

Podophyllotoxin (1) ist einer der bekanntesten Vertreter von natürlich vorkommenden Lignanen. Deoxy‐, epi‐ und Podophyllotoxin, welche alle Vorstufen für häufig verwendete chemotherapeutische Verbindungen darstellen, wurden mithilfe einer stereodivergenten Biotransformation und biokatalytischen kinetischen Racematspaltung der jeweiligen Dibenzylbutyrolactone durch dieselbe 2‐Oxoglutarat‐abhängige Dioxygenase (2‐ODD) hergestellt. Zudem konnte gezeigt werden, dass ein “Upscaling” der Reaktion auf 2 g möglich ist, sowie dass das 2‐ODD‐Enzym Modifikationen des “natürlichen” Substrates toleriert und somit verschiedenste nichtnatürliche Derivate umsetzen kann. Das Enzym führt je nach Substituentenmuster entweder eine oxidative C‐C‐Bindungsbildung durch C‐H‐Aktivierung oder Hydroxylierung an der für die Ringschließung zugänglichen benzylischen Position durch.
Chiral Brønsted Acid Catalyzed Dynamic Kinetic Asymmetric Hydroamination of Racemic Allenes and Asymmetric Hydroamination of Dienes
Authors: Lin Jin‐Shun , Li Tao‐Tao , Jiao Guan‐Yuan , Gu Qiang‐Shuai , Cheng Jiang‐Tao , Lv Ling , Liu Xin‐Yuan
Published: March 2019

The first highly efficient and practical chiral Brønsted acid catalyzed dynamic kinetic asymmetric hydroamination (DyKAH) of racemic allenes and asymmetric hydroamination of unactivated dienes with both high E/Z selectivity and enantioselectivity are described herein. The transformation proceeds through a new catalytic asymmetric model involving a highly reactive π‐allylic carbocationic intermediate, generated from racemic allenes or dienes through a proton transfer mediated by an activating/directing thiourea group. This method affords expedient access to structurally diverse enantioenriched, potentially bioactive alkenyl‐containing aza‐heterocycles and bicyclic aza‐heterocycles.
Circularly‐Polarized Electrochemiluminescence from a Chiral Bispyrene Organic Macrocycle
Authors: Zinna Francesco , Voci Silvia , Arrico Lorenzo , Brun Elodie , Homberg Alexandre , Bouffier Laurent , Funaioli Tiziana , Lacour Jérôme , Sojic Neso , Di Bari Lorenzo
Published: March 2019

The first observation of circular polarization of electrochemiluminescence (ECL) from a purely organic derivative is reported. A bispyrene scaffold mounted on a constrained polyether macrocycle displaying intense excimer fluorescence and highly circularly‐polarized (CP) photoluminescence has been selected for this purpose. The compound displays an ECL dissymmetry factor of about |8×10−3|, which is in good agreement with the corresponding photoluminescence value. This observation is the first step towards the molecular engineering of tailored dyes that can act as both ECL and CP‐ECL reporters for (bio)analysis by bringing a new level of information when dealing with chiral environments. Additionally, it provides an extra dimension to the ECL phenomenon and opens the way to chiral detection and discrimination.
Plasmonic Nickel–TiO2 Heterostructures for Visible‐Light‐Driven Photochemical Reactions
Authors: He Shuai , Huang Jiawei , Goodsell Justin L. , Angerhofer Alexander , Wei Wei David
Published: March 2019

Plasmon‐mediated carrier transfer (PMCT) at metal–semiconductor heterojunctions has been extensively exploited to drive photochemical reactions, offering intriguing opportunities for solar photocatalysis. However, to date, most studies have been conducted using noble metals. Inexpensive materials capable of generating and transferring hot carriers for photocatalysis via PMCT have been rarely explored. Here, we demonstrate that the plasmon excitation of nickel induces the transfer of both hot electrons and holes from Ni to TiO2 in a rationally designed Ni–TiO2 heterostructure. Furthermore, it is discovered that the transferred hot electrons either occupy oxygen vacancies (VO) or produce Ti3+ on TiO2, while the transferred hot holes are located on surface oxygens at TiO2. Moreover, the transferred hot electrons are identified to play a primary role in driving the degradation of methylene blue (MB). Taken together, our results validate Ni as a promising low‐cost plasmonic material for prompting visible‐light photochemical reactions.
High‐Rate, Tunable Syngas Production with Artificial Photosynthetic Cells
Authors: Zhang Hongwen , Ming Jintao , Zhao Jiwu , Gu Quan , Xu Chao , Ding Zhengxin , Yuan Rusheng , Zhang Zizhong , Lin Huaxiang , Wang Xuxu , Long Jinlin
Published: March 2019

An artificial photosynthetic (APS) system consisting of a photoanodic semiconductor that harvests solar photons to split H2O, a Ni‐SNG cathodic catalyst for the dark reaction of CO2 reduction in a CO2‐saturated NaHCO3 solution, and a proton‐conducting membrane enabled syngas production from CO2 and H2O with solar‐to‐syngas energy‐conversion efficiency of up to 13.6 %. The syngas CO/H2 ratio was tunable between 1:2 and 5:1. Integration of the APS system with photovoltaic cells led to an impressive overall quantum efficiency of 6.29 % for syngas production. The largest turnover frequency of 529.5 h−1 was recorded with a photoanodic N‐TiO2 nanorod array for highly stable CO production. The CO‐evolution rate reached a maximum of 154.9 mmol g−1 h−1 in the dark compartment of the APS cell. Scanning electrochemical–atomic force microscopy showed the localization of electrons on the single‐nickel‐atom sites of the Ni‐SNG catalyst, thus confirming that the multielectron reduction of CO2 to CO was kinetically favored.
High Electron Mobility of Amorphous Red Phosphorus Thin Films
Authors: Amaral Pedro E. M. , Nieman Glen P. , Schwenk Gregory R. , Jing Hao , Zhang Raymond , Cerkez Elizabeth B. , Strongin Daniel , Ji Hai‐Feng
Published: March 2019

Black phosphorus (BP) has been gathering great attention for its electronic and optoelectronic applications due to its high electron mobility and high ION/OFF current switching ratio. The limitations of this material include its low synthetic yield and high cost. One alternative to BP is another type of phosphorus allotrope, red phosphorus (RP), which is much more affordable and easier to process. Although RP has been widely used in industry for hundreds of years and considered as an insulating material, in this study, we demonstrate through field‐effect transistors (FET) measurements that amorphous red phosphorus (a‐RP) films are semiconductive with a high mobility of 387 cm2 V−1 s−1 and a current switching ratio of ≈103, which is comparable to the electronic characteristics previously reported for BP. The films were produced via a thermal evaporation method or a facile drop‐casting approach onto Si/SiO2 substrates. We also report a study of the oxidation process of the films over time and a method to stabilize the films via doping a‐RP with metal oxides. The doped films retain stability for one thousand I–V cycles, with no signs of degradation.
Nickel‐Catalyzed Asymmetric Hydrogenation of N‐Sulfonyl Imines
Authors: Li Bowen , Chen Jianzhong , Zhang Zhenfeng , Gridnev Ilya D. , Zhang Wanbin
Published: March 2019

An efficient nickel‐catalyzed asymmetric hydrogenation of N‐tBu‐sulfonyl imines was developed with excellent yields and enantioselectivities using (R,R)‐QuinoxP* as a chiral ligand. The use of a much lower catalyst loading (0.0095 mol %, S/C=10500) represents the highest catalytic activity for the Ni‐catalyzed asymmetric hydrogenations reported so far. Mechanistic studies suggest that a coordination equilibrium exists between the nickel salt and its complex, and that excess nickel salt promotes the formation of the active Ni‐complex, and therefore improved the efficiency of the hydrogenation. The catalytic cycle was also investigated by calculations to determine the origin of the enantioselectivity. An extensive network of numerous weak attractive interactions was found to exist between the catalyst and substrate in the transition state and may also contribute to the high catalytic activity.
Synthesis of Poly(N‐vinylamide)s and Poly(vinylamine)s and Their Block Copolymers by Organotellurium‐Mediated Radical Polymerization
Authors: Fan Weijia , Yamago Shigeru
Published: March 2019

Controlled polymerization of acyclic N‐vinylamides, that is, N‐methyl‐N‐vinylacetamide (NMVA), N‐vinylacetamide (NVA), and N‐vinylformamide (NVF), by organotellurium‐mediated radical polymerization (TERP) is reported. The corresponding poly(N‐vinylamide)s with controlled molecular weight and low dispersity (Ð<1.25) were obtained with high monomer conversion in all cases. This is the first report on the controlled polymerization of NVF. Hydrolysis of the polymers, in particular PNVF, occurred quantitatively under mild reaction conditions, giving structurally controlled poly(vinylamine)s. Block copolymers containing poly(N‐vinylamide) and poly(vinylamine) segments were also synthesized in a controlled manner.
Total Synthesis of (−)‐Daphenylline
Authors: Xu Bo , Wang Bingyang , Xun Wen , Qiu Fayang G.
Published: March 2019

A concise and highly stereoselective total synthesis of the Daphniphyllum alkaloids (−)‐daphenylline has been accomplished. The synthesis was started from (S)‐carvone and proceeded via a stereoselective Mg(ClO4)2‐catalyzed intramolecular amide addition cyclization, an intramolecular Diels–Alder reaction to construct the ABCD tetracyclic core architecture, and a Robinson annulation coupled with an oxidative aromatization sequence. Finally, the DF ring system was installed through an intramolecular Friedel–Crafts cyclization. The total synthesis of (−)‐daphenylline is achieved in 19 steps in the longest reaction sequence and in 7.6 % overall yield.
A Self‐Assembled Bicontinuous Cubic Phase with a Single‐Diamond Network
Authors: Zeng Xiangbing , Poppe Silvio , Lehmann Anne , Prehm Marko , Chen Changlong , Liu Feng , Lu Huanjun , Ungar Goran , Tschierske Carsten
Published: March 2019

The first single‐diamond cubic phase in a liquid crystal is reported. This skeletal structure with the
space group is formed by self‐assembly of bolaamphiphiles with swallow‐tailed lateral chains. It consists of bundles of π‐conjugated p‐terphenyl rods fused into an infinite network by hydrogen‐bonded spheres at tetrahedral four‐way junctions. We also present a quantitative model relating molecular architecture to the space‐filling requirements of six possible bicontinuous cubic phases, that is, the single‐ and double‐network versions of gyroid, diamond, and “plumber′s nightmare”.
Efficient Synthesis of α‐Trifluoromethyl Carboxylic Acids and Esters through Fluorocarboxylation of gem‐Difluoroalkenes
Authors: Yoo Woo‐Jin , Kondo Junpei , Rodríguez‐Santamaría José A. , Nguyen Thanh V. Q. , Kobayashi Shū
Published: March 2019

A facile synthetic procedure for the preparation of α‐trifluoromethyl carboxylic acids and esters was achieved through multicomponent coupling reactions between gem‐difluoroalkenes, cesium fluoride, and carbon dioxide. The products were generated in moderate to excellent yields, and the synthetic utility of this method was demonstrated through the preparation of trifluoromethylated versions of popular nonsteroidal anti‐inflammatory drugs (NSAIDs).
Three pairs of enantiomers bearing mitochondria‐targeted TPP+ groups as potential anti‐cancer agents
Authors: Liu Yue , Song Xue‐Qing , Li Si‐Tong , Liu Xin , Tian Jin‐Lei , Xu Jing‐Yuan , Yan Shi‐Ping
Published: March 2019

Six complexes with chiral Schiff‐base ligands containing TPP+ groups, [VOLR,R/S,S](ClO4)2(1 for RR, 2 for SS), [NiLR,R/S,S](ClO4)2·C2H5OH (3 for RR, 4 for SS) and [CuLR,R/S,S](ClO4)2·CHCl3·CH3CH2OH (5 for RR, 6 for SS) (LR,R/S,S = N,N′‐Bis{5‐[(triphenylphosphonium)‐methyl]salicylidine}‐(1R,2R/1S,2S)‐diphenylethane‐1,2‐diamine, were synthesized to serve as mitochondrion‐targeting anticancer drugs. The introduction of TPP+ group(s) might markedly influence the properties of complexes. Compounds 3 and 5 were structurally characterized by X‐ray crystallography. Complexes 1–6 could be moderate intercalating agents to CT‐DNA which is determined by several spectroscopy methods. DNA cleavage experiments revealed that all compounds could promote oxidative cleavage of pBR322 plasmid DNA in the presence of H2O2. MTT assay indicated 1–6 exhibited effective cytotoxicity on A549 and MCF‐7 cell lines. Notably, the IC50 values of 5 (1.24 ± 0.33 μM) or 6 (1.47 ± 0.52 μM) were approximately 9–11 fold lower than that of cisplatin (IC50 = 13.56 ± 0.88 μM) on A549 cells. 5 and 6 were picked for further study, which indicated that the cytotoxicity seems to result from multiple mechanisms of action, including effectively suppress the growth and proliferation of A549 cells, generation of reactive oxygen species, dissipation of mitochondrial membrane potential, cell cycle perturbation and apoptosis induction. Compounds 1–6 could highly accumulate in the mitochondria by means of ICP‐MS assay. This study demonstrates that 1–6 with mitochondrion‐targeting function could be efficient anticancer drugs.
Guideline Implementation: Design and Maintenance of the Surgical Suite
Authors: Link Terri
Published: March 2019

The primary considerations for any health care facility construction or renovation project are the design and function of the new areas, assessment of environmental risks for airborne contamination, and containment of dust and moisture created during construction activities. Disruptions created by construction inside or outside a health care facility can increase airborne organisms, such as Aspergillus, that can lead to infections; thus, infection prevention and control are integral parts of construction planning. The AORN “Guideline for design and maintenance of the surgical suite” provides guidance to perioperative team members for developing a functional program to guide the construction/renovation project, use of evidence‐based design principles, measures to contain construction‐related dust and debris, and maintenance of utilities after planned or emergent utility failures. Perioperative nurses should review the complete guideline for additional information and for guidance when writing and updating policies and procedures.
Quaternized chitosan/functionalized carbon nanotubes composite anion exchange membranes
Authors: Jang Shin‐Cheng , Chuang Fu‐Sheng , Tsen Wen‐Chin , Kuo Ting‐Wei
Published: March 2019

Natural alkaline polyelectrolyte chitosan has been considered to be a promising anion exchange membrane (AEM) material due to its low cost and easy quaternization. To further improve the ionic conductivity and mechanical property of quaternized chitosan (QCS), QCS functionalized carbon nanotubes (QCS@CNTs) were prepared and used as a novel nanofiller to modify the membrane matrix. The QCS coating layer on the surface of CNTs can not only improve the dispersion of CNTs and thus promote the load transfer from the QCS matrix to stiff CNTs, but also endow CNTs with a certain hydroxide ions exchange ability. The results show that the addition of QCS@CNTs slightly decreased the ionic conductivity of the composite membranes while the tensile strength and alkaline stability of these membranes were significantly improved, indicating the potential application of these composite membranes in AEM fuel cells. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2019,136, 47778.
Synthesis of aminophosphonate polyols and polyurethane foams with improved fire retardant properties
Authors: Borreguero Ana M. , Velencoso María M. , Rodríguez Juan F. , Serrano Ángel , Carrero M. José , Ramos María J.
Published: March 2019

Aminophosphonated polyols with flame retardant properties are synthesized by ring opening polymerization using diethyl‐N,N‐bis(2‐hydroxyethyl) aminomethyl phosphonate (Fyrol‐6) as initiator. The influence of the catalyst type and its concentration on the polymerization rate are studied. The catalyst system formed by potassium methoxide (MeOK) in DMSO as a solvent presents the highest polymerization rate and allows reducing the polydispersity. The thermal resistance of the synthesized polyols is confirmed by the char residues formation. Finally, PU foams are synthesized containing up to a 50 pph of PFyCs[1:1], preserving good cellular structure up to a 25 pph content and improving the fire resistance by increasing the char residue from 7.79 to 22.13 wt % and decreasing the PHRR and the smoke production according to TGA and cone calorimeter tests, respectively. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47780.
A Machine Learning Classifier for Assigning Individual Patients With Systemic Sclerosis to Intrinsic Molecular Subsets
Authors: Franks Jennifer M. , Martyanov Viktor , Cai Guoshuai , Wang Yue , Li Zhenghui , Wood Tammara A. , Whitfield Michael L.
Published: March 2019

Objective

High‐throughput gene expression profiling of tissue samples from patients with systemic sclerosis (SSc) has identified 4 “intrinsic” gene expression subsets: inflammatory, fibroproliferative, normal‐like, and limited. Prior methods required agglomerative clustering of many samples. In order to classify individual patients in clinical trials or for diagnostic purposes, supervised methods that can assign single samples to molecular subsets are required. We undertook this study to introduce a novel machine learning classifier as a robust accurate intrinsic subset predictor.

Methods

Three independent gene expression cohorts were curated and merged to create a data set covering 297 skin biopsy samples from 102 unique patients and controls, which was used to train a machine learning algorithm. We performed external validation using 3 independent SSc cohorts, including a gene expression data set generated by an independent laboratory on a different microarray platform. In total, 413 skin biopsy samples from 213 individuals were analyzed in the training and testing cohorts.

Results

Repeated cross‐fold validation identified consistent and discriminative markers using multinomial elastic net, performing with an average classification accuracy of 87.1% with high sensitivity and specificity. In external validation, the classifier achieved an average accuracy of 85.4%. Reanalyzing data from a previous study, we identified subsets of patients that represent the canonical inflammatory, fibroproliferative, and normal‐like subsets.

Conclusion

We developed a highly accurate classifier for SSc molecular subsets for individual patient samples. The method can be used in SSc clinical trials to identify an intrinsic subset on individual samples. Our method provides a robust data‐driven approach to aid clinical decision‐making and interpretation of heterogeneous molecular information in SSc patients.
Inca astronomy: Horizon, light, and shadow
Authors: Gullberg S. R.
Published: March 2019

The Incas worshipped the Sun, with light and shadow effects in their constructs commonly denoting such events as the solstices and equinoxes. They also honored and venerated many features of both natural and man‐made landscapes, which they felt to be endowed with superhuman powers. In Quechua, these shrines were known ashuacas, and at the time of the Spanish conquest there were thousands of them. Soon after subduing the Inca empire, the Spaniards began a campaign against the indigenous religion, which included a systematic eradication of huacas. Shrines that were large carved stones and outcroppings survived, however, and were subjects of this research for astronomical orientations marking significant solar events. Examples of Inca astronomy are explored in this paper. The approach is a holistic one in that it considers multiples levels of meaning including cultural motifs, topographic and astronomical contexts, sightlines, as well as light and shadow effects throughout the year, especially at times of the solstice, equinox, zenith, and anti‐zenith suns. Astronomy was thoroughly interwoven throughout many facets of Inca society.
Relativistic X‐ray jets at high redshift
Authors: Schwartz Daniel , Siemiginowska Aneta , Worrall Diana , Birkinshaw Mark , Cheung Teddy , Marshall Herman , Migliori Giulia , Wardle John , Gobeille Doug
Published: March 2019

Powerful radio sources and quasars emit relativistic jets of plasma and magnetic fields that travel hundreds of kiloparsecs, ultimately depositing energy into the intra‐ or inter‐cluster medium. In the rest frame of the jet, the energy density of the cosmic microwave background is enhanced by the bulk Lorentz factor as Γ2, and when this exceeds the magnetic energy density the primary loss mechanism of the relativistic electrons is via inverse Compton scattering. The microwave energy density
is also enhanced by a factor (1 + z)4, which becomes important at large redshifts. We are surveying a z > 3 subsample of radio sources selected with centimeter‐wavelength flux density >70 mJy, and with a spectroscopic redshift. Out of the first 12 objects observed, there are two clear cases of the X‐rays extending beyond the detectable radio jet.
CoLiTecVS – A new tool for the automated reduction of photometric observations
Authors: Kudzej I. , Savanevych V. E. , Briukhovetskyi O. B. , Khlamov S. V. , Pohorelov A. V. , Vlasenko V. P. , Dubovský P. A. , Parimucha Š.
Published: March 2019

The capabilities of telescopes allow the plotting of light curves a routine task. This one shifts the main attention of the astronomer from plotting to research. To achieve this goal, we developed a new tool for the automated reduction of photometric observations, which includes the computational method for the brightness assessment of the investigated and comparison stars, brightness equalization of astronomical images using an inverse median filter, as well as light curve plotting and processing using different tools.
Regge–Wheeler and Zerilli equations within a modified theory of general relativity
Authors: Hess Peter O. , López‐Moreno Enrique
Published: March 2019

An r‐dependent term is added to the metric for the study of extensions of the Theory of General Relativity (GR). The stability of the Schwarzschild solution is investigated with and without the presence of this additional term. Polar (Zerilli) and axial (Regge–Wheeler) modes are studied and the differences discussed. The main conclusion is that, with an r‐dependent term in the metric, the axial and polar modes remain stable. Assuming that GR describes the data of the gravitational wave events, in the modified theory, axial modes involve larger masses, which might change the interpretation of the source of the gravitational wave events observed.
Neutrino emissivity in the color superconducting quark‐hadron‐mixed phase
Authors: Freeman A. , Farrell D. , Weber F. , Spinella W. M. , Orsaria M. G. , Contrera G. A.
Published: March 2019

The tremendously high pressures that exist in the cores of neutron stars may break up neutrons, protons plus other hadronic particles into their quark constituents. This transition from hadronic matter to quark matter could lead to an extended quark‐hadron‐mixed phase region in the cores of neutron stars that would segregate phases by net charge to minimize the total energy of the phase, leading to the formation of a crystalline quark‐hadron Coulomb lattice. The neutrino emissivity due to the elastic scattering of electrons off the lattice was previously studied where it was assumed that the quark lattice sites are made of ordinary (i.e., nonsuperconducting) quark structures (blobs, rods, and slabs). In the present study, we extend these calculations to the elastic scattering of electrons off quark blobs that are in the color superconducting color‐flavor‐locked (CFL) phase. As this phase reduces the electric charge carried by quark blobs, the electric charge density of CFL blobs is smaller than that of non‐CFL blobs. The neutrino emission rates, however, change only minimally.
Contribution of quantum chromodynamics condensates to the operator product expansion of Green functions of chiral currents
Authors: Kadavý T. , Kampf K. , Novotný J.
Published: March 2019

In this paper, the basic properties of quantum chromodynamics (QCD) condensates are presented, together with theirs relation to the operator product expansion (OPE) and the two‐point and three‐point Green functions constructed of chiral currents. Next, our newest results for the contribution of the QCD condensates with dimension D < 6 to the Green functions calculated within the framework of χPT/RχT, i.e. chiral perturbation theory or resonance chiral theory, are discussed. This matching of the OPE and such effective theories can lead to some constraints on the coupling constants, thus allowing us to obtain some unknown parameters of the chiral/resonance Lagrangian.
Effective field theory with genuine many‐body forces and tidal effects on neutron stars
Authors: Razeira M. , Hadjimichef D. , Machado M. V. T. , Köpp F. , Volkmer G. , Bodmann B. , Degrazia G. A. , Vasconcellos C. A. Z.
Published: March 2019

Neutron stars are characterized by their masses, radii, spinning speeds (associated with their moments of inertia), and degree of deformation. Under the action of an external static tidal quadrupole field ℰij, the neutron star undergoes a deformation measured in terms of the ratio between the quadrupole moment induced in the star and the field ℰij, which defines, in turn, the tidal deformability parameter. In this contribution, we combine our recent predictions for the neutron stars' tidal parameter with recent gravitational wave observations of merging the binary system GW170817 with quasiuniversal relations between the maximum mass of rotating and nonrotating neutron stars. Our results indicate that predictions of the tidal parameter represent a useful constraint of the Equation of State (EoS) of neutron stars.
The complex phenomena of young stellar objects revealed by their X‐ray variability
Authors: Sciortino S. , Flaccomio E. , Pillitteri I. , Reale F.
Published: March 2019

X‐ray observations of young stellar objects (YSOs) have shown several complex phenomena at work. In recent years, a few X‐ray programs based on long, continuous, and, sporadically, simultaneous coordinated multiwavelength observations have paved the way to our current understanding of the physical processes at work, which very likely regulates the interaction between the star and its circumstellar disk. We will present and discuss some recent results based on a novel analysis of a few selected very large flares observed with the Chandra Orion Ultradeep Pointing, on the systematic analysis of a large collection of flares observed with the Coordinated Synoptic Investigation of NGC 2264 (CSI 2264) as well as on the Class I/II YSO Elias 29, in the rho Oph star forming region, whose data have been recently gathered as part of a joint simultaneous XMM‐Newton and NuSTAR large program.
Metal−Organic Frameworks for High‐Energy Lithium Batteries with Enhanced Safety: Recent Progress and Future Perspectives
Authors: Zhang Xiahui , Dong Panpan , Song Min‐Kyu
Published: March 2019

Metal−organic frameworks (MOFs) are a relatively new class of crystalline, highly‐porous organic‐inorganic hybrid materials that have been attracting increasing attention in the field of high‐energy lithium batteries. In this review, recent achievements are detailed regarding the innovative design and processing of pristine MOFs and their nanocomposites for lithium−sulfur and lithium−oxygen batteries with high specific energy. Furthermore, the benefits and challenges associated with the applications of MOF‐based materials in solid‐state lithium‐metal batteries are discussed. Lastly, future prospects for the rational design and manufacturing of MOF‐based materials are provided.
Risk factors associated with the development of double‐inlet ventricle congenital heart disease
Authors: Paige Sharon L. , Yang Wei , Priest James R. , Botto Lorenzo D. , Shaw Gary M. , Collins Ronnie Thomas ,   the National Birth Defects Prevention Study
Published: March 2019

Background

Congenital heart disease (CHD) is the most common birth defect group and a significant contributor to neonatal and infant death. CHD with single ventricle anatomy, including hypoplastic left heart syndrome (HLHS), tricuspid atresia (TA), and various double‐inlet ventricle (DIV) malformations, is the most complex with the highest mortality. Prenatal risk factors associated with HLHS have been studied, but such data for DIV are lacking.

Methods

We analyzed DIV cases and nonmalformed controls in the National Birth Defects Prevention Study, a case‐control, multicenter population‐based study of birth defects. Random forest analysis identified potential predictor variables for DIV, which were included in multivariable models to estimate effect magnitude and directionality.

Results

Random forest analysis identified pre‐pregnancy diabetes, history of maternal insulin use, maternal total lipid intake, paternal race, and intake of several foods and nutrients as potential predictors of DIV. Logistic regression confirmed pre‐pregnancy diabetes, maternal insulin use, and paternal race as risk factors for having a child with DIV. Additionally, higher maternal total fat intake was associated with a reduced risk.

Conclusions

Maternal pre‐pregnancy diabetes and history of insulin use were associated with an increased risk of having an infant with DIV, while maternal lipid intake had an inverse association. These novel data provide multiple metabolic pathways for investigation to identify better the developmental etiologies of DIV and suggest that public health interventions targeting diabetes prevention and management in women of childbearing age could reduce CHD risk.
Extracellular Vesicles from Mesenchymal Stem Cells Exert Pleiotropic Effects on Amyloid‐β, Inflammation, and Regeneration: A Spark of Hope for Alzheimer's Disease from Tiny Structures?
Authors: Elia Chiara A. , Losurdo Morris , Malosio Maria L. , Coco Silvia
Published: March 2019

No cure yet exists for devastating Alzheimer's disease (AD), despite many years and humongous efforts to find efficacious pharmacological treatments. So far, neither designing drugs to disaggregate amyloid plaques nor tackling solely inflammation turned out to be decisive. Mesenchymal stem cells (MSCs) and, in particular, extracellular vesicles (EVs) originating from them could be proposed as an alternative, strategic approach to attack the pathology. Indeed, MSC‐EVs—owing to their ability to deliver lipids/proteins/enzymes/microRNAs endowed with anti‐inflammatory, amyloid‐β degrading, and neurotrophic activities—may be exploited as therapeutic tools to restore synaptic function, prevent neuronal death, and slow down memory impairment in AD. Herein the results presented in the most recently published studies on this topic are critically evaluated, providing a strong rationale for possible employment of MSC‐EVs in AD. Also see the video abstract here https://youtu.be/tBtDbnlRUhg.
Hypercapnia downregulates hypoxia‐induced lysyl oxidase expression in pulmonary artery smooth muscle cells via inhibiting transforming growth factor β1 signalling
Authors: Xia Xiao‐dong , Peng Yan‐ping , Lei Dan , Chen Wei‐qian
Published: March 2019

Hypoxic pulmonary arterial hypertension is characterized by elevated pulmonary vascular resistance and remodelling. Transforming growth factor‐β1 (TGF‐β1) is the master regulator in cellular response to hypoxia which can directly target lysyl oxidase (LOX). This study aimed to determine whether hypercapnia attenuates hypoxic pulmonary hypertension via regulating TGF‐β1 and LOX signalling. We found that exposure to hypercapnia ameliorated the increase in mean pulmonary artery pressure (mPAP) and ratio of right ventricle to left ventricle plus septum (RV/(LV + S)) induced by hypoxia but had no effect on mPAP and RV/(LV + S) in normoxia‐exposed control. In addition, exposure to hypoxia upregulated the mRNA and protein levels of LOX and TGF‐β1 in rat PASMCs both in vivo and in vitro, but these effects were abrogated by concurrent exposure to hypercapnia. The downregulation of LOX in rat PASMCs induced by hypercapnia was reversed by the administration with TGF‐β1, while TGF‐β1 knockdown repressed the upregulation of LOX in hypoxia‐exposed rat PASMCs. In conclusion, hypoxia upregulates LOX and TGF‐β1 expression in PASMCs and contributes to pulmonary hypertension. Hypercapnia downregulates hypoxia‐induced LOX expression and alleviates hypoxia‐associated pulmonary hypertension via inhibiting TGF‐β1 signalling.

Significance of the Study

Hypoxia‐induced upregulation of TGF‐β1, PDGF, and HIF‐1α plays a pivotal role in PAH, but molecular mechanism of how hypoxia regulates LOX expression is not clear. In the present study, we showed that mRNA and protein expression levels of LOX were substantially increased when TGF‐β1 was induced by hypoxia, and the effects were reversed by TGF‐β1 knockdown. Our study indicates that TGF‐β1 is implicated in the regulation of LOX.
Oxygen‐Deficient Ti0.9Nb0.1O2‐x as an Efficient Anodic Catalyst Support for PEM Water Electrolyzer
Authors: Lv Hong , Wang Sen , Hao Chuanpu , Zhou Wei , Li Jiakun , Xue Mingzhe , Zhang Cunman
Published: March 2019

Herein, the low cost and efficient oxygen‐deficient Ti0.9Nb0.1O2‐x as support of IrO2 (noted as IrO2/TNO) anode catalyst for the PEM water electrolyzer is synthesized and then characterized using a series of techniques. Oxygen vacancies are introduced by hydrogenation treatment. The IrO2/TNO sample after hydrogenation (noted as IrO2/TNO−Hx, x corresponds to the hydrogenation temperature) exhibits enhanced electronic conductivity and increased surface active sites relative to that of the pristine IrO2/TNO sample. A single cell is assembled by IrO2/TNO−Hx as anode catalyst, commercial Pt/C as cathode catalytic and Nafion 117 membrane as electrolyte. At a low loading mass of IrO2, the IrO2/TNO−H750 sample shows the optimum oxygen evolution reaction (OER) activity (1.832 V at 1 A ⋅ cm−2), which is superior to that of unsupported IrO2 (1.858 eV at 1 A ⋅ cm−2), and remains stable for 100 h operating at a current density of 1 A cm−2. This work provides a rational design strategy for developing low cost and efficient anode catalysts support.
Ti−Pd Alloys as Heterogeneous Catalysts for the Hydrogen Autotransfer Reaction and Catalytic Improvement by Hydrogenation Effects
Authors: Takahashi Yuya , Kondo Ryota , Utsunomiya Masayoshi , Suzuki Takeyuki , Takeshita Hiroyuki T. , Obora Yasushi
Published: March 2019

Ti−Pd alloys were investigated as heterogeneous catalysts for hydrogen autotransfer reactions. This is the first reported study of alloys as catalysts for hydrogen‐borrowing reactions using alcohols. We improved the catalytic activities of alloys by increasing their specific surface areas via a hydrogenation−powdering process. The reactivities and selectivities of hydrogenated Ti−Pd alloys [Ti−Pd(Hy)] were higher than those of non‐hydrogenated alloy catalysts in N‐alkylation by hydrogen autotransfer using alcohols. A plausible catalytic cycle is proposed based on control studies and deuterium labelling experiments.
Progressive Freeze Concentration for Volume Reduction of Produced Water and Biodiesel Wastewater
Authors: Samsuri Shafirah , Rizan Nor Aman Nor , Hung Siew Hzien , Amran Nurul Aini , Sambudi Nonni Soraya
Published: March 2019

One way to conserve fresh water resources is by reusing water from wastewater. For instance, water can be removed from wastewater through formation of ice crystal layers by progressive freeze concentration (PFC). The application of PFC to remove water from produced water and biodiesel wastewater was assessed through the final concentration of concentrated wastewater and purity of melted ice crystals. No PFC study has been done on these applications. In order to evaluate the efficiency of PFC, the effective partition constant (K) and separation efficiency (SE) were calculated for the effect of stirring rate and coolant temperature. The results demonstrate that PFC is a more practical method for produced water, as compared to biodiesel wastewater which is based on the value of low K and high SE.
Engineering of Hierarchical and Three‐Dimensional Architectures Constructed by Titanium Nitride Nanowire Assemblies for Efficient Electrocatalysis
Authors: Liu Fangfang , Yang Xu , Dang Dai , Tian Xinlong
Published: March 2019

Electrocatalysts that exhibit both, high performance and durability are essential for the promotion and commercialization of energy conversion devices. Transition metal nitrides (TMNs) hold great potential in many electrochemical catalytic processes, whereas the rational syntheses of highly open and three‐dimensional titanium nitride‐based nanostructures through a facile and efficient strategy is still a challenge. Herein, a scalable and effective method is proposed for the rational synthesis of mono‐ or bi‐metallic titanium nitride with three‐dimensional urchin‐like porous structures, which exhibit high electrochemical stability and structure durability. When being used as the support, the resultant electrocatalyst possesses much higher activity and durability in oxygen reduction reaction as well as methanol oxidation reaction. This work provides a general approach for the rational design of TMN‐based electrocatalysts or devices for application in energy conversion and storage technologies.
Photochemical, Metal‐Free Sigmatropic Rearrangement Reactions of Sulfur Ylides
Authors: Yang Zhen , Guo Yujing , Koenigs Rene M.
Published: March 2019

Sigmatropic rearrangement reactions constitute one of the most fundamental reactions of carbenes. While state‐of‐the‐art synthetic methods require the use of expensive precious metal catalysts, the application of visible light for the photolysis of α‐aryldiazoacetates is much less investigated and provides an operationally simple entry to carbenes under mild reaction conditions. Herein, we report on blue‐light induced sigmatropic rearrangement reactions of sulfur compounds with α‐aryldiazoacetates. This process, depending on the substitution pattern of the sulfide, opens up formal insertion reactions of carbenes into S−N, S−C, or C−H bonds.
Mechanistic Insights into Statistical Co‐Assembly of Metal Complexes
Authors: Coelho Joao Paulo , Matern Jonas , Albuquerque Rodrigo Q. , Fernández Gustavo
Published: March 2019

Statistical copolymerization plays a key role in many biological and technological processes; however, mechanistic understanding of the formation of analogous supramolecular counterparts remains limited. Herein, we report detailed insights into the supramolecular co‐assembly of two π‐conjugated PdII and PtII complexes, which in isolation self‐assemble into flexible fibers and nanodisks, respectively. An efficient single‐step co‐assembly into only one type of nanostructure (fibers or nanodisks) takes place if any of the components is in excess. In contrast, equimolar mixtures lead to PdII‐rich fiber‐like co‐assemblies by a statistical co‐nucleation event along with a residual amount of self‐sorted nanodisks in a stepwise manner.
Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long‐term survival follow‐up from the randomized, phase 3 INO‐VATE study
Authors: Kantarjian Hagop M. , DeAngelo Daniel J. , Stelljes Matthias , Liedtke Michaela , Stock Wendy , Gökbuget Nicola , O’Brien Susan M. , Jabbour Elias , Wang Tao , Liang White Jane , Sleight Barbara , Vandendries Erik , Advani Anjali S.
Published: March 2019

Background

Inotuzumab ozogamicin (InO) is an antibody‐drug conjugate used for adults with relapsed/refractory B‐cell precursor (BCP) acute lymphoblastic leukemia (ALL). The INotuzumab Ozogamicin trial to inVestigAte Tolerability and Efficacy (INO‐VATE) previously reported improved outcomes with InO versus standard‐of‐care (SoC) chemotherapy. This article reports the final INO‐VATE results (≥2 years of follow‐up) and additional analyses of patient characteristics associated with improved outcomes.

Methods

Between August 27, 2012, and January 4, 2015, this multicenter, parallel, open‐label, phase 3 trial randomized 326 adults with relapsed/refractory ALL to InO (n = 164) or SoC (n = 162); 307 received 1 or more doses of the study drug (164 in the InO arm and 143 in the SoC arm).

Results

The complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) rate was higher with InO versus SoC (73.8% vs 30.9%; 1‐sided P < .0001), with consistent CR/CRi rates across patient subgroups. The median overall survival (OS) was 7.7 months with InO and 6.2 months with SoC, with 2‐year OS rates of 22.8% and 10.0%, respectively (overall hazard ratio, 0.75; 97.5% confidence interval [CI], 0.57‐0.99; 1‐sided P = .0105). The predictors of OS with InO were the best minimal residual disease status, baseline platelet count, duration of first remission, achievement of CR/CRi, and follow‐up hematopoietic stem cell transplantation (HSCT; all 2‐sided P values < .05). More InO arm patients proceeded directly to HSCT after achieving CR/CRi before any follow‐up induction therapy (39.6% [95% CI, 32.1%‐47.6%] vs 10.5% [6.2%‐16.3%]; 1‐sided P < .0001). The most frequent all‐grade and grade 3 or higher adverse events in both arms were hematologic. Veno‐occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) was more frequent with InO (23 of 164 [14.0%] vs 3 of 143 [2.1%]).

Conclusions

In patients with relapsed/refractory BCP ALL in INO‐VATE, InO was associated with a greater likelihood of CR/CRi across key patient subgroups, and it served as a bridge to HSCT. Potential VOD/SOS risk factors must be considered when InO treatment decisions are being made.
Safety Profiles, Pharmacokinetics, and Changes in Bone Turnover Markers After Twice‐Weekly Subcutaneous Administration of Teriparatide in Healthy Japanese Postmenopausal Women: A Single‐Blind Randomized Study
Authors: Kumagai Yuji , Ose Atsushi , Tanaka Kosuke , Sugimoto Toshitsugu
Published: March 2019

Once‐weekly injection of 56.5‐μg teriparatide formulation is a potent therapeutic agent for osteoporosis treatment. However, this treatment has an issue of difficulty in continuing the treatment by its adverse side effects including nausea, vomiting, and headaches. To reduce these adverse side effects, we conducted a randomized, single‐blind, placebo‐controlled study to examine the pharmacokinetics, changes in bone turnover markers, and safety profiles of twice‐weekly 28.2‐μg teriparatide injections. Different dosing intervals of the twice‐weekly 28.2‐μg injections were also studied. A total of 100 healthy Japanese postmenopausal women were enrolled in this multiple‐dosing study. The systemic exposure of teriparatide acetate in the twice‐weekly 28.2‐μg injection was half that of the once‐weekly 56.5‐μg injection. Changes in bone turnover markers in the twice‐weekly 28.2‐μg injection were comparable to those in the once‐weekly 56.5‐μg injection. Incidences of adverse events including nausea, vomiting, and headaches were lower in the twice‐weekly 28.2‐μg injections than those in the once‐weekly 56.5‐μg injection. Findings were similar in the twice‐weekly 28.2‐μg injections regardless of the dosing interval. Thus, the new dosing regimen using twice‐weekly 28.2‐μg injections maintained comparable efficacy to the once‐weekly 56.5‐μg injections; however, it improved the safety profile and contributed to better continuity of care with teriparatide.
Enhancement of the Electrical Properties of DNA Molecular Wires through Incorporation of Perylenediimide DNA Base Surrogates
Authors: Lin Kuo‐Yao , Burke Anthony , King Nolan B. , Kahanda Dimithree , Mazaheripour Amir , Bartlett Andrew , Dibble David J. , McWilliams Marc A. , Taylor David W. , Jocson Jonah‐Micah , Minary‐Jolandan Majid , Gorodetsky Alon A. , Slinker Jason D.
Published: March 2019

DNA has long been viewed as a promising material for nanoscale electronics, in part due to its well‐ordered arrangement of stacked, pi‐conjugated base pairs. Within this context, a number of studies have investigated how structural changes, backbone modifications, or artificial base substitutions affect the conductivity of DNA. Herein, we present a comparative study of the electrical properties of both well‐matched and perylene‐3,4,9,10‐tetracarboxylic diimide (PTCDI)‐containing DNA molecular wires that bridge nanoscale gold electrodes. By performing current‐voltage measurements for such devices, we find that the incorporation of PTCDI DNA base surrogates within our macromolecular constructs leads to an approximately 6‐fold enhancement in the observed current levels. Together, these findings suggest that PTCDI DNA base surrogates may enable the preparation of designer DNA‐based nanoscale electronic components.
Light‐Powered Self‐Sustainable Macroscopic Motion for the Active Locomotion of Materials
Authors: Kageyama Yoshiyuki
Published: March 2019

The creation of small robots comprised of tiny molecules is an intriguing research theme for chemists. Recently, there have been remarkable reports of photoresponsive molecules that exhibit mechanical function. Light‐driven multimolecular robots will likely soon be a commercial reality. However, most light‐actuated materials do not move self‐continuously; thus, microrobots made of these materials must have external controls. To create a drone‐type molecular robot, a self‐governing mechanism for mechanical movements must be installed. This Minireview summarizes recent reports of light‐driven materials that are capable of locomotion. By proposing a very simple model and numerical analysis to describe strategies for continuous motion, this paper shows that the coupling of nonlinear phenomena is the key underlying the self‐regulation of reactions in these materials, offering important design insights for researchers.
OMIP‐056: Evaluation of Human Conventional T Cells, Donor‐Unrestricted T Cells, and NK Cells Including Memory Phenotype by Intracellular Cytokine Staining
Authors: Dintwe One , Rohith Shamiska , Schwedhelm Katharine V. , McElrath M. Juliana , Andersen‐Nissen Erica , De Rosa Stephen C.
Published: March 2019

A 26‐color staining panel was developed to profile human antigen‐specific T cells in an intracellular cytokine staining (ICS) assay using peptide pools to various antigens of interest. In addition to multiple functional markers, the panel includes differentiation/activation markers and markers to assess γδ, mucosal‐associated invariant T, and NK T cells as well as conventional NK cells. Panel optimization was performed using previously cryopreserved PBMC from healthy adults, and then, expression of key functional markers in the panel was cross‐validated against a validated ICS assay used in the HIV Vaccine Trials Network (HVTN). The panel is currently being used to evaluate the responses to tuberculosis and malaria vaccine candidates in volunteers from different geographic areas. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
Generation of Nppa‐tagBFP reporter knock‐in mouse line for studying cardiac chamber specification
Authors: Zhang Zhentao , Zhang Qinkun , Lal Hind , Nam Young‐Jae
Published: March 2019

Nppa is a cardiac hormone which plays critical roles in regulating salt–water balance. Its expression is restricted to the atria of the healthy post‐natal heart. During heart development, spatio‐temporal expression of Nppa is dynamically changed within the heart and becomes restricted to the atria upon birth. In contrast to its atrial specific expression after birth, Nppa is re‐expressed in the adult ventricles in response to cardiac hypertrophy. To study cardiac chamber specification during development and pathological cardiac remodeling during heart disease, we generated a novel Nppa reporter mouse line by knocking‐in a tagBFP reporter cassette into 3′‐UTR of the Nppa gene without disrupting the endogenous gene. Our results demonstrated dynamic tagBFP expression in the developing heart, recapitulating the spatiotemporal expression pattern of endogenous Nppa. We also found that Nppa‐tagBFP is induced in the ventricle during pathological remodeling. Taken together, Nppa‐tagBFP reporter knock‐in mouse model described in this article will serve as a valuable tool to study cardiac chamber specification during development as well as pathological cardiac remodeling.