bluuebunny/crossref_metadata_2025 huggingface dataset:
N‐Heterocyclic‐Carbene‐Catalyzed Stereoselective Annulations: An Efficient Strategy for the Synthesis of Chromeno[4,3‐b]pyrrolidine Derivatives
Authors: Qi Jing , Duan Xiao‐Yong , Cao Li‐Li , Wang Wen‐Ying
Published: September 2015

An N‐heterocyclic‐carbene‐catalyzed annulation of alkynyl aldehydes and o‐hydroxy aromatic aldimines for the construction of chromeno[4,3‐b]pyrrolidine derivatives has been developed. This cascade Michael/Mannich/lactonization process constructs three new bonds and three consecutive stereogenic centers in a single step with excellent diastereoselectivity and low catalyst loading.
Rhodium(III)‐Catalyzed Allylic C(sp3)–H Activation of Alkenyl Sulfonamides: Unexpected Formation of Azabicycles
Authors: Archambeau Alexis , Rovis Tomislav
Published: September 2015

Unsaturated N‐sulfonamides undergo a RhIII‐ catalyzed allylic C(sp3)H activation followed by insertion with an exogenous internal alkyne. The reaction generates [3.3.0], [4.3.0], and [5.3.0] azabicyclic structures with excellent diastereoselectivity. Deuterium labeling experiments implicate a 1,3‐Rh shift as a key step in the mechanism.
Rerouting Electron Transfer in Molecular Assemblies by Redox‐Pair Matching
Authors: Balgley Renata , Shankar Sreejith , Lahav Michal , van der Boom Milko E.
Published: September 2015

We demonstrate how the distance over which electron transfer occurs through organic materials can be controlled and extended. Coating of conductive surfaces with nanoscale layers of redox‐active metal complexes allows the electrochemical addressing of distant layers that are otherwise electrochemically silent. Our materials can pass electrons selectively in directions that are determined by positioning of layers of metal complexes and the distances between them. These electron‐transfer processes can be made dominantly uni‐ or bidirectional. The design involves 1) a set of isostructural metal complexes with different electron affinities, 2) a scalable metal–organic spacer, and 3) a versatile assembly approach that allows systematic variation of composition, structure, and electron‐transfer properties. We control the electrochemical communication between interfaces by the deposition sequence and the spacer length, therefore we are able to program the bulk properties of the assemblies.
Activity‐Directed Synthesis with Intermolecular Reactions: Development of a Fragment into a Range of Androgen Receptor Agonists
Authors: Karageorgis George , Dow Mark , Aimon Anthony , Warriner Stuart , Nelson Adam
Published: September 2015

Activity‐directed synthesis (ADS), a novel discovery approach in which bioactive molecules emerge in parallel with associated syntheses, was exploited to develop a weakly binding fragment into novel androgen receptor agonists. Harnessing promiscuous intermolecular reactions of carbenoid compounds enabled highly efficient exploration of chemical space. Four substrates were prepared, yet exploited in 326 reactions to explore diverse chemical space; guided by bioactivity alone, the products of just nine of the reactions were purified to reveal diverse novel agonists with up to 125‐fold improved activity. Remarkably, one agonist stemmed from a novel enantioselective transformation; this is the first time that an asymmetric reaction has been discovered solely on the basis of the biological activity of the product. It was shown that ADS is a significant addition to the lead generation toolkit, enabling the efficient and rapid discovery of novel, yet synthetically accessible, bioactive chemotypes.
Palladium‐Catalyzed Heteroarylation and Concomitant ortho‐Alkylation of Aryl Iodides
Authors: Lei Chuanhu , Jin Xiaojia , Zhou Jianrong (Steve)
Published: September 2015

Three‐component couplings were achieved from common aryl halides, alkyl halides, and heteroarenes under palladium and norbornene co‐catalysis. The reaction forges hindered aryl–heteroaryl bonds and introduces ortho‐alkyl groups to aryl rings. Various heterocycles such as oxazoles, thiazoles and thiophenes underwent efficient coupling. The heteroarenes were deprotonated in situ by bases without the assistance of palladium catalysts.
Copper‐Mediated Formation of Aryl, Heteroaryl, Vinyl and Alkynyl Difluoromethylphosphonates: A General Approach to Fluorinated Phosphate Mimics
Authors: Ivanova Maria V. , Bayle Alexandre , Besset Tatiana , Poisson Thomas , Pannecoucke Xavier
Published: September 2015

A general and efficient access to aryl, heteroaryl, vinyl and alkynyl difluoromethylphosphonates is described. The developed methodology using TMSCF2PO(OEt)2, iodonium salts and a copper salt provided a straightforward manifold to reach these highly relevant products. The reaction proved to be highly functional group tolerant and proceeded under mild conditions, giving the corresponding products in good to excellent yields. This method represents the first general synthetic route to this important class of fluorinated scaffolds, which are well‐recognized as in vivo stable phosphate surrogates.
Bioorthogonal Enzymatic Activation of Caged Compounds
Authors: Ritter Cornelia , Nett Nathalie , Acevedo‐Rocha Carlos G. , Lonsdale Richard , Kräling Katja , Dempwolff Felix , Hoebenreich Sabrina , Graumann Peter L. , Reetz Manfred T. , Meggers Eric
Published: September 2015

Engineered cytochrome P450 monooxygenase variants are reported as highly active and selective catalysts for the bioorthogonal uncaging of propargylic and benzylic ether protected substrates, including uncaging in living E. coli. observed selectivity is supported by induced‐fit docking and molecular dynamics simulations. This proof‐of‐principle study points towards the utility of bioorthogonal enzyme/protecting group pairs for applications in the life sciences.
Endothelial Cells Expressing Endothelial and Mesenchymal Cell Gene Products in Lung Tissue From Patients With Systemic Sclerosis–Associated Interstitial Lung Disease
Authors: Mendoza Fabian A. , Piera‐Velazquez Sonsoles , Farber John L. , Feghali‐Bostwick Carol , Jiménez Sergio A.
Published: September 2015

Objective

To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)–associated interstitial lung disease (ILD) express mesenchymal cell–specific proteins and gene transcripts, indicative of the occurrence of endothelial‐to‐mesenchymal phenotypic transition (EndoMT).

Methods

Lung tissue from 6 patients with SSc‐associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc‐associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed by quantitative polymerase chain reaction, immunofluorescence microscopy, and Western blotting.

Results

Immunohistochemical staining revealed cells expressing the EC‐specific marker CD31 in the subendothelial, perivascular, and parenchymal regions of the lungs from all SSc patients. Confocal microscopy identified cells displaying simultaneous expression of von Willebrand factor and α‐smooth muscle actin in small and medium‐sized arterioles in the SSc lung tissue but not in normal control lungs. CD31+CD102+ ECs isolated from SSc lungs expressed high levels of mesenchymal cell–specific genes (type I collagen, type III collagen, and fibronectin), EC‐specific genes (type IV collagen and VE‐cadherin), profibrotic genes (transforming growth factor β1 and connective tissue growth factor), and genes encoding EndoMT‐related transcription factors (TWIST1 and SNAI2).

Conclusion

Cells coexpressing EC‐ and mesenchymal cell–specific molecules are present in the lungs of patients with SSc‐associated ILD. CD31+CD102+ ECs isolated from SSc lungs simultaneously expressed mesenchymal cell– and EC‐specific transcripts and proteins. Collectively, these observations demonstrate the occurrence of EndoMT in the lungs of patients with SSc‐associated ILD.
Short‐Term Total Hip Arthroplasty Outcomes in Patients With Psoriatic Arthritis or Psoriatic Skin Disease Compared to Patients With Osteoarthritis
Authors: Mandl Lisa A. , Zhu Rebecca , Huang Wei‐Ti , Zhang Meng , Alexiades Michael M. , Figgie Mark P. , Goodman Susan M.
Published: September 2015

Objective

Outcomes of total hip arthroplasty (THA) in patients with psoriasis have been poorly studied. This study was undertaken to assess whether patients with psoriatic arthritis (PsA) or those with cutaneous psoriasis (PsC) without evidence of inflammatory joint disease are at an increased risk for worse outcomes after THA as compared to patients with osteoarthritis (OA).

Methods

Among subjects in a prospective THA registry, PsA and PsC cases were identified by International Classification of Diseases, Ninth Revision codes, and all cases were matched with patients with OA as controls. Analyses were performed to identify predictors of poor postoperative pain or function.

Results

Of the 289 potential cases of PsA or PsC, 63 with PsA and 153 with PsC were validated. Self‐report data were available postoperatively from 75% of PsA patients, 69% of PsC patients, and 94% of OA controls. In total, 51% of PsA patients and 56% of PsC patients were male, compared to 45% of OA controls (P = 0.04). Body mass index was higher in those with PsA or PsC (P = 0.002 versus controls). There were no differences in race or education between the 3 groups. PsA patients and PsC patients had more comorbidities than OA controls. PsA patients were more likely than PsC patients and OA controls to be current or previous smokers. Moreover, 54% of PsA patients were being treated with biologics or nonbiologic disease‐modifying antirheumatic drugs, compared to 8% of PsC patients. There were no significant differences in pre‐ or postoperative Western Ontario and McMaster Universities OA Index scores for pain or function between the 3 groups. Short‐Form 36 mental component summary scores were significantly better in the OA controls, both pre‐ and postoperatively (P = 0.006 and P < 0.001, respectively, versus PsA or PsC). EuroQol 5‐domain health‐related quality of life scores were significantly worse postoperatively for those with PsA or PsC (P < 0.0001 versus OA controls). In regression analyses, neither PsA nor PsC were risk factors for worse THA outcomes. Satisfaction with the outcomes of THA was similarly high among all 3 groups (P = 0.54).

Conclusion

Neither PsA nor PsC are risk factors for poor outcomes after THA. This is important information to convey to patients with either PsA or PsC who are contemplating surgical intervention with THA.
Variable stars in the Bochum Galactic Disk Survey
Authors: Kaderhandt L. , Barr Domínguez A. , Chini R. , Hackstein M. , Haas M. , Pozo Nuñez F. , Murphy M.
Published: September 2015

We present a first overview of variable stars in the Bochum Galactic Disk Survey (GDS) with emphasis on eclipsing binaries (EBs). This ongoing survey is performed by a robotic twin refractor at the Universitätssternwarte Bochum located near Cerro Armazones in Chile. It comprises a mosaic of 268 fields in a stripe of Δb = ±3° along the Galactic plane observed once per month simultaneously in the Sloan r and i filters with a detection limit of rs ∼ 16 mag and is ∼ 15 mag. The data from the first three years until the end of February 2014 yields a total of 41718 variable stars with variability amplitudes between 0.1–6 mag. A cross‐match with SIMBAD identified 11 465 of these variables unambiguously, while 2184 had multiple matches; most of the remaining stars could be matched with 2MASS objects. Among the SIMBAD‐listed objects with single matches, only 1982 turned out as known variables while a further 256 are suspected of variability. That leaves a total of 39480 potentially new variables. The group of known variables comprises 419 stars (21 %) that are classified as EBs while 443 (22%) are of other types; for the remaining 1120 catalogued variables (57 %) the type is unknown. Investigating variability as a function of spectral type, we find that SIMBAD provides spectral types for 2811 (25 %) of the identified stars. Spectral classes B (26 %), A (20 %), and M (25%) contain the most numerous variables, while all other classes contribute less than 10% each. More than half of the B (55 %) and A (56%) stars are designated as EBs, suggesting that hundreds of new B‐ and A‐type EBs may be contained in the GDS archive. In contrast, among the numerous M stars no EBs are known. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Formation of accretion centers in simulations of colliding uniform density H2 cores
Authors: Arreaga‐García G. , Klapp J.
Published: September 2015

We test here the first stage of a route of modifications to be applied to the public GADGET2 code for dynamically identifying accretion centers during the collision process of two adjacent and identical gas cores. Each colliding core has a uniform density profile and rigid body rotation; its mass and size have been chosen to represent the observed core L1544; for the thermal and rotational energy ratios with respect to the potential energy, we assume the values α = 0.3 and β = 0.1, respectively. These values favor the gravitational collapse of the core. We here study cases of both head‐on and off‐center collisions, in which the pre‐collision velocity increases the initial sound speed of the barotropic gas by up to several times. In a simulation the accretion centers are formed by the highest density particles, so we here report their location and properties in order to realize the collision effects on the collapsing and colliding cores. In one of the models, we observe a roughly spherical distribution of accretion centers located at the front wave of the collision. In a forthcoming publication we will apply the full modified GADGET code to study the collision of turbulent cores. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Bivariate correlation coefficients in family‐type clustered studies
Authors: Luo Jingqin , D'Angelo Gina , Gao Feng , Ding Jimin , Xiong Chengjie
Published: September 2015

We propose a unified approach based on a bivariate linear mixed effects model to estimate three types of bivariate correlation coefficients (BCCs), as well as the associated variances between two quantitative variables in cross‐sectional data from a family‐type clustered design. These BCCs are defined at different levels of experimental units including clusters (e.g., families) and subjects within clusters and assess different aspects on the relationships between two variables. We study likelihood‐based inferences for these BCCs, and provide easy implementation using standard software SAS. Unlike several existing BCC estimators in the literature on clustered data, our approach can seamlessly handle two major analytic challenges arising from a family‐type clustered design: (1) many families may consist of only one single subject; (2) one of the paired measurements may be missing for some subjects. Hence, our approach maximizes the use of data from all subjects (even those missing one of the two variables to be correlated) from all families, regardless of family size. We also conduct extensive simulations to show that our estimators are superior to existing estimators in handling missing data or/and imbalanced family sizes and the proposed Wald test maintains good size and power for hypothesis testing. Finally, we analyze a real‐world Alzheimer's disease dataset from a family clustered study to investigate the BCCs across different modalities of disease markers including cognitive tests, cerebrospinal fluid biomarkers, and neuroimaging biomarkers.
Network meta‐analysis with integrated nested Laplace approximations
Authors: Sauter Rafael , Held Leonhard
Published: September 2015

Analyzing the collected evidence of a systematic review in form of a network meta‐analysis (NMA) enjoys increasing popularity and provides a valuable instrument for decision making. Bayesian inference of NMA models is often propagated, especially if correlated random effects for multiarm trials are included. The standard choice for Bayesian inference is Markov chain Monte Carlo (MCMC) sampling, which is computationally intensive. An alternative to MCMC sampling is the recently suggested approximate Bayesian method of integrated nested Laplace approximations (INLA) that dramatically saves computation time without any substantial loss in accuracy. We show how INLA apply to NMA models for summary level as well as trial‐arm level data. Specifically, we outline the modeling of multiarm trials and inference for functional contrasts with INLA. We demonstrate how INLA facilitate the assessment of network inconsistency with node‐splitting. Three applications illustrate the use of INLA for a NMA.
Engineering the hematopoietic stem cell niche: Frontiers in biomaterial science
Authors: Choi Ji Sun , Mahadik Bhushan P. , Harley Brendan A. C.
Published: September 2015

Hematopoietic stem cells (HSCs) play a crucial role in the generation of the body's blood and immune cells. This process takes place primarily in the bone marrow in specialized 'niche' microenvironments, which provide signals responsible for maintaining a balance between HSC quiescence, self‐renewal, and lineage specification required for life‐long hematopoiesis. While our understanding of these signaling mechanisms continues to improve, our ability to engineer them in vitro for the expansion of clinically relevant HSC populations is still lacking. In this review, we focus on development of biomaterials‐based culture platforms for in vitro study of interactions between HSCs and their local microenvironment. The tools and techniques used for both examining HSC‐niche interactions as well as applying these findings towards controlled HSC expansion or directed differentiation in 2D and 3D platforms are discussed. These novel techniques hold the potential to push the existing boundaries of HSC cultures towards high‐throughput, real‐time, and single‐cell level biomimetic approaches that enable a more nuanced understanding of HSC regulation and function. Their application in conjunction with innovative biomaterial platforms can pave the way for engineering artificial bone marrow niches for clinical applications as well as elucidating the pathology of blood‐related cancers and disorders.
Minimal genome: Worthwhile or worthless efforts toward being smaller?
Authors: Choe Donghui , Cho Suhyung , Kim Sun Chang , Cho Byung‐Kwan
Published: September 2015

Microbial cells are versatile hosts for the production of value‐added products due to the well‐established background knowledge, various genetic tools, and ease of manipulation. Despite those advantages, efficiency of newly incorporated synthetic pathways in microbial cells is frequently limited by innate metabolism, product toxicity, and growth‐mediated genetic instability. To overcome those obstacles, a minimal genome harboring only the essential set of genes was proposed, which is a fascinating concept with potential for use as a platform strain. Here, we review the currently available artificial reduced genomes and discuss the prospects for extending use of the genome‐reduced strains as programmable chasses. The genome‐reduced strains generally showed comparable growth to and higher productivity than their ancestral strains. In Escherichia coli, about 300 genes are estimated as the minimal number of genes under laboratory conditions. However, recent advances revealed that there are non‐essential components in essential genes, suggesting that the design principle of minimal genomes should be reconstructed. Current technology is not efficient enough to reduce large amount of interspaced genomic regions or to synthesize the genome. Furthermore, construction of minimal genome frequently has failed due to lack of genomic information. Technological breakthroughs and intense systematic studies on genomes remain tasks.
Polyphosphate as a metabolic fuel in Metazoa: A foundational breakthrough invention for biomedical applications
Authors: Wang Xiaohong , Schröder Heinz C. , Müller Werner E. G.
Published: September 2015

In animals, energy‐rich molecules like ATP are generated in the intracellular compartment from metabolites, e.g. glucose, taken up by the cells. Recent results revealed that inorganic polyphosphates (polyP) can provide an extracellular system for energy transport and delivery. These polymers of multiple phosphate units, linked by high‐energy phosphoanhydride bonds, use blood platelets as transport vehicles to reach their target cells. In this review it is outlined how polyP affects cell metabolism. It is discussed that polyP influences cell activity in a dual way: (i) as a metabolic fuel transferring metabolic energy through the extracellular space; and (ii) as a signaling molecule that amplifies energy/ATP production in mitochondria. Several metabolic pathways are triggered by polyP, among them biomineralization/hydroxyapatite formation onto bone cells. The accumulation of polyP in the platelets allows long‐distance transport of the polymer in the extracellular space. The discovery of polyP as metabolic fuel and signaling molecule initiated the development of novel techniques for encapsulation of polyP into nanoparticles. They facilitate cellular uptake of the polymer by receptor‐mediated endocytosis and allow the development of novel strategies for therapy of metabolic diseases associated with deviations in energy metabolism or mitochondrial dysfunctions.
Epigenetic Alterations Associated with War Trauma and Childhood Maltreatment
Authors: Ramo‐Fernández Laura , Schneider Anna , Wilker Sarah , Kolassa Iris‐Tatjana
Published: September 2015

Survivors of war trauma or childhood maltreatment are at increased risk for trauma‐spectrum disorders such as post‐traumatic stress disorder (PTSD). In addition, traumatic stress has been associated with alterations in the neuroendocrine and the immune system, enhancing the risk for physical diseases. Traumatic experiences might even affect psychological as well as biological parameters in the next generation, i.e. traumatic stress might have transgenerational effects. This article outlines how epigenetic processes, which represent a pivotal biological mechanism for dynamic adaptation to environmental challenges, might contribute to the explanation of the long‐lasting and transgenerational effects of trauma. In particular, epigenetic alterations in genes regulating the hypothalamus–pituitary–adrenal axis as well as the immune system have been observed in survivors of childhood and adult trauma. These changes could result in enduring alterations of the stress response as well as the physical health risk. Furthermore, the effects of parental trauma could be transmitted to the next generation by parental distress and the pre‐ and postnatal environment, as well as by epigenetic marks transmitted via the germline. While epigenetic research has a high potential of advancing our understanding of the consequences of trauma, the findings have to be interpreted with caution, as epigenetics only represent one piece of a complex puzzle of interacting biological and environmental factors. Copyright © 2015 John Wiley & Sons, Ltd.
Epigenetics and Child Psychiatry: Ethical and Legal Issues
Authors: Thomas Christopher R.
Published: September 2015

Epigenetics has the potential to revolutionize diagnosis and treatment in psychiatry, especially child psychiatry, as it may offer the opportunity for early detection and prevention, as well as development of new treatments. As with the previous introduction of genetic research in psychiatry, there is also the problem of unrealistic expectations and new legal and ethical problems. This article reviews the potential contributions and problems of epigenetic research in child psychiatry. Previous legal and ethical issues in genetic research serve as a guide to those in epigenetic research. Recommendations for safeguards and guidelines on the use of epigenetics with children and adolescents are outlined based on the identified issues. Copyright © 2015 John Wiley & Sons, Ltd.
Involvement of Lipocalin‐like CghA in Decalin‐Forming Stereoselective Intramolecular [4+2] Cycloaddition
Authors: Sato Michio , Yagishita Fumitoshi , Mino Takashi , Uchiyama Nahoko , Patel Ashay , Chooi Yit‐Heng , Goda Yukihiro , Xu Wei , Noguchi Hiroshi , Yamamoto Tsuyoshi , Hotta Kinya , Houk Kendall N. , Tang Yi , Watanabe Kenji
Published: September 2015

Understanding enzymatic Diels–Alder (DA) reactions that can form complex natural product scaffolds is of considerable interest. Sch 210972 1, a potential anti‐HIV fungal natural product, contains a decalin core that is proposed to form through a DA reaction. We identified the gene cluster responsible for the biosynthesis of 1 and heterologously reconstituted the biosynthetic pathway in Aspergillus nidulans to characterize the enzymes involved. Most notably, deletion of cghA resulted in a loss of stereoselective decalin core formation, yielding both an endo (1) and a diastereomeric exo adduct of the proposed DA reaction. Complementation with cghA restored the sole formation of 1. Density functional theory computation of the proposed DA reaction provided a plausible explanation of the observed pattern of product formation. Based on our study, we propose that lipocalin‐like CghA is responsible for the stereoselective intramolecular [4+2] cycloaddition that forms the decalin core of 1.
Ion‐Transport Processes in Dual‐Ion Cells Utilizing a Pyr1,4TFSI/LiTFSI Mixture as the Electrolyte
Authors: Balabajew Marco , Kranz Tobias , Roling Bernhard
Published: September 2015

In dual‐ion cells, the extraction of ions from the electrolyte during charging leads to the formation of ion concentration gradients and to ion transport processes. In order to obtain information about these processes, we examine changes in the electrolyte resistance in an exemplary dual‐ion cell utilizing a Pyr1,4TFSI/LiTFSI mixture as electrolyte. The negative and the positive electrode are metallic lithium and graphite, respectively. The individual changes in the electrolyte resistance in both half‐cells are monitored in situ by means of three‐electrode electrochemical impedance spectroscopy. The results are compared to finite element simulations, for which concentration‐dependent diffusion and conductivity data of Pyr1,4TFSI/LiTFSI mixtures are used as input parameters. We show that differences in the mobilities of the three types of ions play a decisive role for the time evolution of the ion concentration gradients and the resulting resistance changes in the two half‐cells.
Mesoporous Silica Nanoparticles Decorated with Carbosilane Dendrons as New Non‐viral Oligonucleotide Delivery Carriers
Authors: Martínez Ángel , Fuentes‐Paniagua Elena , Baeza Alejandro , Sánchez‐Nieves Javier , Cicuéndez Mónica , Gómez Rafael , de la Mata F. Javier , González Blanca , Vallet‐Regí María
Published: September 2015

A novel nanosystem based on mesoporous silica nanoparticles covered with carbosilane dendrons grafted on the external surface of the nanoparticles is reported. This system is able to transport single‐stranded oligonucleotide into cells, avoiding an electrostatic repulsion between the cell membrane and the negatively charged nucleic acids thanks to the cationic charge provided by the dendron coating under physiological conditions. Moreover, the presence of the highly ordered pore network inside the silica matrix would make possible to allocate other therapeutic agents within the mesopores with the aim of achieving a double delivery. First, carbosilane dendrons of second and third generation possessing ammonium or tertiary amine groups as peripheral functional groups were prepared. Hence, different strategies were tested in order to obtain their suitable grafting on the outer surface of the nanoparticles. As nucleic acid model, a single‐stranded DNA oligonucleotide tagged with a fluorescent Cy3 moiety was used to evaluate the DNA adsorption capacity. The hybrid material functionalised with the third generation of a neutral dendron showed excellent DNA binding properties. Finally, the cytotoxicity as well as the capability to deliver DNA into cells, was tested in vitro by using a human osteoblast‐like cell line, achieving good levels of internalisation of the vector DNA/carbosilane dendron‐functionalised material without affecting the cellular viability.
Insertion/Rearrangement Reactivity of a Lutetacyclopentadiene towards N,N′‐Diphenylcarbodiimide: Cooperative Effect of the Metal Center, Concentration of LiCl, and Solvent
Authors: Xu Ling , Wei Junnian , Zhang Wen‐Xiong , Xi Zhenfeng
Published: September 2015

The reactivity of lutetacyclopentadiene towards N,N′‐diphenylcarbodiimide (DPC) was systematically investigated to efficiently construct three types of new N‐containing fused cyclic complexes. The outcome of these reactions significantly depended on the the metal center, the concentration of LiCl, the number of equivalents of DPC, and the solvent. Thus, two unexpected reaction modes of amidinate were discovered for the first time, which were ascribed to an unusual κ1 coordination mode of amidinate driven by a rigid seven‐membered ring. These results are in striking contrast with the previously well‐investigated zirconacyclopentadiene, which reacts with DPC to give azazirconacyclopentene and alkyne through β,β′ CC bond cleavage. The difference in reactivity between lutetacyclopentadiene and zirconacyclopentadiene can be attributed to the highly ionic character of the LuC(sp2) bonds. DFT calculations agreed well with the experimental results.
PdII‐Catalyzed Intermolecular Amination of Unactivated C(sp3)H Bonds
Authors: Gou Quan , Liu Gang , Liu Zi‐Ning , Qin Jun
Published: September 2015

PdII‐catalyzed intermolecular amination of unactivated C(sp3)H bonds has been successfully developed for the first time. This method provides a new way to achieve the challenging intermolecular amination of unactivated C(sp3)H bonds, producing a variety of unnatural β2‐amino carboxylic acid analogues. This C(sp3)H amination protocol is demonstrated with a broad substrate scope, good functional‐group tolerance, and chemoselectivity. It is operated without use of phosphine ligand or external oxidant.
Photocyclodehydrofluorination
Authors: Li Zhe , Twieg Robert J.
Published: September 2015

Mallory‐type photocyclization involves a series of photoreactions of stilbenes, o‐terphenyls and related derivatives, which undergo intramolecular cyclization via dihydrophenanthrene intermediates. In typical Mallory photocyclizations, oxidants are usually needed to produce the final phenanthrene‐containing product. In the research described here, appropriately fluorinated stilbenes and o‐terphenyls undergo ring closure and HF is eliminated. This photocyclodehydrofluorination (PCDHF) reaction is very useful to produce a wide range of selectively fluorinated polynuclear aromatic hydrocarbons that possess a phenanthrene (or heterocyclic analogue of phenanthrene) substructure. These fluorinated products are of great interest in various aspects of the materials science.
Prins Cyclization Catalyzed by a FeIII/Trimethylsilyl Halide System: The Oxocarbenium Ion Pathway versus the [2+2] Cycloaddition
Authors: Pérez Sixto J. , Purino Martín , Miranda Pedro O. , Martín Víctor S. , Fernández Israel , Padrón Juan I.
Published: September 2015

The different factors that control the alkene Prins cyclization catalyzed by iron(III) salts have been explored by means of a joint experimental–computational study. The iron(III) salt/trimethylsilyl halide system has proved to be an excellent promoter in the synthesis of crossed all‐cisdisubstituted tetrahydropyrans, minimizing the formation of products derived from side‐chain exchange. In this iron(III)‐catalyzed Prins cyclization reaction between homoallylic alcohols and non‐activated alkenes, two mechanistic pathways can be envisaged, namely the classical oxocarbenium route and the alternative [2+2] cycloaddition‐based pathway. It is found that the [2+2] pathway is disfavored for those alcohols having non‐activated and non‐substituted alkenes. In these cases, the classical pathway, via the key oxocarbenium ion, is preferred. In addition, the final product distribution strongly depends upon the nature of the substituent adjacent to the hydroxy group in the homoallylic alcohol, which can favor or hamper a side 2‐oxonia‐Cope rearrangement.
Hierarchical Mesoporous Metal–Organic Frameworks for Enhanced CO2 Capture
Authors: Mao Yiyin , Chen Danke , Hu Pan , Guo Yi , Ying Yulong , Ying Wen , Peng Xinsheng
Published: September 2015

Hierarchical porous materials are promising for catalyst, separation and sorption applications. A ligand‐assisted etching process is developed for template‐free synthesis of hierarchical mesoporous MOFs as single crystals and well‐intergrown membranes at 40 °C. At 223 K, the hierarchical porous structures significantly improve the CO2 capture capacity of HKUST‐1 by more than 44 % at pressures up to 20 kPa and 13 % at 100 kPa. Even at 323 K, the enhancement of CO2 uptake is above 25 % at pressures up to 20 kPa and 7 % at 100 kPa. The mesoporous structures not only enhance the CO2 uptake capacity but also improve the diffusion and mass transportation of CO2. Similarly, well‐intergrown mesoporous HKUST‐1 membranes are synthesized, which hold the potential for film‐like porous devices. Mesoporous MOF‐5 crystals are also obtained by a similar ligand‐assisted etching process. This may provide a facile way to prepare hierarchical porous MOF single crystals and membranes for wide‐ranging applications.
Magnesium(I) Dimers Bearing Tripodal Diimine–Enolate Ligands: Proficient Reagents for the Controlled Reductive Activation of CO2 and SO2
Authors: Boutland Aaron J. , Pernik Indrek , Stasch Andreas , Jones Cameron
Published: September 2015

The first examples of magnesium(I) dimers bearing tripodal ligands, [(Mg{κ3‐N,N′,O‐(ArNCMe)2(OCCPh2)CH})2] [Ar=2,6‐iPr2C6H3 (Dip) 7, 2,6‐Et2C6H3 (Dep) 8, or mesityl (Mes) 9] have been prepared by post‐synthetic modification of the β‐diketiminato ligands of previously reported magnesium(I) systems, using diphenylketene, OCCPh2. In contrast, related reactions between β‐diketiminato magnesium(I) dimers and the isoelectronic ketenimine, MesNCCPh2, resulted in reductive insertion of the substrate into the MgMg bond of the magnesium(I) reactant, and formation of [{(Nacnac)Mg}2{μ‐κ2‐N,C‐(Mes)NCCPh2}] (Nacnac=[(ArNCMe)2CH]−; Ar=Dep 10 or Mes 11). Reactions of the four‐coordinate magnesium(I) dimer 8 with excess CO2 are readily controlled, and cleanly give carbonate [(LMg)2(μ‐κ2:κ2‐CO3)] 12 (L=[κ3‐N,N′,O‐(DepNCMe)2(OCCPh2)CH]−; thermodynamic product), or oxalate [(LMg)2(μ‐κ2:κ2‐C2O4)] 13 (kinetic product), depending on the reaction temperature. Compound 12 and CO are formed by reductive disproportionation of CO2, whereas 13 results from reductive coupling of two molecules of the gas. Treatment of 8 with an excess of N2O cleanly gives the μ‐oxo complex [(LMg)2(μ‐O)] 14, which reacts facilely with CO2 to give 12. This result presents the possibility that 14 is an intermediate in the formation of 12 from the reaction of 8 and CO2. In contrast to its reactions with CO2, 8 reacts with SO2 over a wide temperature range to give only one product; the first example of a magnesium dithionite complex, [(LMg)2(μ‐κ2:κ2‐S2O4)] 16, which is formed by reductive coupling of two molecules of SO2, and is closely related to f‐block metal dithionite complexes derived from similar SO2 reductive coupling processes. On the whole, this study strengthens previously proposed analogies between the reactivities of magnesium(I) systems and low‐valent f‐block metal complexes, especially with respect to small molecule activations.
Access to Highly Functionalized Sulfonated Cyclopentanes by Acid‐Promoted Rauhut–Currier Reaction with Sulfinamides
Authors: Gigant Nicolas , Drège Emmanuelle , Retailleau Pascal , Joseph Delphine
Published: September 2015

An unexpected acid‐mediated cascade reaction induced by conjugate addition of sulfinamides to dienediones has been developed. This highly efficient Rauhut–Currier reaction enables the rapid, high‐yielding construction of sulfonated cyclopentanes with three contiguous stereogenic centers in a single operation starting from simple sulfinamides. This process constitutes the first example of sulfinamide‐promoted cycloisomerization.
Brain region‐dependent differential expression of alpha‐synuclein
Authors: Taguchi Katsutoshi , Watanabe Yoshihisa , Tsujimura Atsushi , Tanaka Masaki
Published: September 2015

α‐Synuclein, the major constituent of Lewy bodies (LBs), is normally expressed in presynapses and is involved in synaptic function. Abnormal intracellular aggregation of α‐synuclein is observed as LBs and Lewy neurites in neurodegenerative disorders, such as Parkinson's disease (PD) or dementia with Lewy bodies. Accumulated evidence suggests that abundant intracellular expression of α‐synuclein is one of the risk factors for pathological aggregation. Recently, we reported differential expression patterns of α‐synuclein between excitatory and inhibitory hippocampal neurons. Here we further investigated the precise expression profile in the adult mouse brain with special reference to vulnerable regions along the progression of idiopathic PD. The results show that α‐synuclein was highly expressed in the neuronal cell bodies of some early PD‐affected brain regions, such as the olfactory bulb, dorsal motor nucleus of the vagus, and substantia nigra pars compacta. Synaptic expression of α‐synuclein was mostly accompanied by expression of vesicular glutamate transporter‐1, an excitatory presynaptic marker. In contrast, expression of α‐synuclein in the GABAergic inhibitory synapses was different among brain regions. α‐Synuclein was clearly expressed in inhibitory synapses in the external plexiform layer of the olfactory bulb, globus pallidus, and substantia nigra pars reticulata, but not in the cerebral cortex, subthalamic nucleus, or thalamus. These results suggest that some neurons in early PD‐affected human brain regions express high levels of perikaryal α‐synuclein, as happens in the mouse brain. Additionally, synaptic profiles expressing α‐synuclein are different in various brain regions. J. Comp. Neurol. 524:1236–1258, 2016. © 2015 Wiley Periodicals, Inc.
In situ Formation of a Monodispersed Spherical Mesoporous Nanosilica–Torlon Hollow‐Fiber Composite for Carbon Dioxide Capture
Authors: Rownaghi Ali A. , Rezaei Fateme , Labreche Ying , Brennan Patrick J. , Johnson Justin R. , Li Fuyue Stephanie , Koros William J.
Published: September 2015

We describe a new template‐free method for the in situ formation of a monodispersed spherical mesoporous nanosilica–Torlon hollow‐fiber composite. A thin layer of Torlon hollow fiber that comprises silica nanoparticles was created by the in situ extrusion of a tetraethyl orthosilicate/N‐methyl‐2‐pyrrolidone solution in a sheath layer and a Torlon polymer dope in a core support layer. This new method can be integrated easily into current hollow‐fiber composite fabrication processes. The hollow‐fiber composites were then functionalized with 3‐aminopropyltrimethoxy silane (APS) and evaluated for their CO2‐capture performance. The resulting APS‐functionalized mesoporous silica nanoparticles/Torlon hollow fibers exhibited a high CO2 equilibrium capacity of 1.5 and 1.9 mmol g−1 at 35 and 60 °C, respectively, which is significantly higher than values for fiber sorbents without nanoparticles reported previously.
Cell surface markers and exogenously induced PpIX in synovial mesenchymal stem cells
Authors: Denkovskij Jaroslav , Rudys Romualdas , Bernotiene Eiva , Minderis Mindaugas , Bagdonas Saulius , Kirdaite Gailute
Published: September 2015

The aim of present study was to assess the expression of surface markers and the accumulation of protoporphyrin IX in synovial mesenchymal stem cells (SMSCs). SMSC from patients with rheumatoid arthritis (RA, n = 5) and osteoarthritis (OA, n = 5–6) were characterized and their PpIX accumulation rates were evaluated by flow cytometry. The expression of the 21 out of 24 tested surface markers, related to stem‐like features and aggressiveness of cells showed no statistically significant differences between RA and OA groups. However, the cells from RA group had the significantly lower levels of expression for the integrin‐associated protein CD47 and the grow factor receptor CD271 (P = 0.018), while the higher levels of cell membrane zinc‐dependent metalloproteinase CD10 (P = 0.006), as compared to the cells from OA group. Comparison of the mean intensities of PpIX fluorescence revealed no statistically significant differences between the RA and OA groups, as well as no relation to proliferation rates or cell size, although some conspicuous distinction in PpIX accumulation was observed in certain specimens within these groups, suggesting possibilities of this method application for characterization of individual SMSC populations. CD10, CD47, and CD271 were differently expressed in RA and OA SMSC, while had no direct association with the PpIX fluorescence intensity. © 2015 International Society for Advancement of Cytometry
Optimal spectrum sensing and transmission power allocation in energy‐efficiency multichannel cognitive radio with energy harvesting
Authors: Liu Xin , Jia Min , Gu Xue‐mai , Yan Jun‐hua , Zhou Jian‐jiang
Published: September 2015

We consider an energy‐efficiency multichannel cognitive radio (CR) where the secondary user (SU) can harvest the signal energy from the primary user (PU) to supply the power transmission. The goal of this paper is to determine an optimal joint spectrum sensing and transmission power allocation that maximizes the average throughput of the multichannel SU over all the subchannels subject to the constraints of subchannel sensing probabilities, interference power, and total transmission power. The SU harvests the PU energy, which is then converted into electrical energy and stored in the battery if the presence of the PU is detected, while consuming the stored energy to transmit data if the absence of the PU is detected. The allocation scheme is formulated as a joint optimization problem of spectrum sensing time and subchannel transmission power vector, whose optimal solution is obtained through the joint optimization algorithm based on alternating direction optimization. Analytical and numerical results show that the proposed energy‐efficiency CR outperforms the traditional CR without energy harvesting, and the transmission power of the energy‐efficiency CR improves both with the increasing of the spectrum sensing time and the presence probability of the PU. Copyright © 2015 John Wiley & Sons, Ltd.
Cytochrome P450‐mediated metabolism of the synthetic cannabinoids UR‐144 and XLR‐11
Authors: Nielsen Line Marie , Holm Niels Bjerre , Olsen Lars , Linnet Kristian
Published: September 2015

In recent years, synthetic cannabinoids have emerged in the illicit drug market, in particular via the Internet, leading to abuse of these drugs. There is currently limited knowledge about the specific enzymes involved in the metabolism of these drugs. In this study, we investigated the cytochrome P450 (CYP) enzymes involved in the metabolism of the two synthetic cannabinoids (1‐pentyl‐1H‐indol‐3‐yl)‐(2,2,3,3‐tetramethylcyclopropyl)methanone (UR‐144) and [1‐(5‐fluoropentyl)‐1H‐indol‐3‐yl)](2,2,3,3‐tetramethylcyclopropyl)methanone (XLR‐11). This study extends previous studies by identifying the specific CYP enzymes involved in the metabolism of UR‐144 and XLR‐11 utilizing a panel of nine recombinant enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 3A4, and 2E1). This is followed by an investigation of the effect of specific inhibitors targeted against CYP1A2, 2B6, 2C9, 2C19, 2D6 and 3A4 in human liver microsomes (HLM). Incubations of UR‐144 and XLR‐11 with recombinant CYP enzymes revealed that UR‐144 and XLR‐11 are extensively metabolized by CYP3A4 at the tetramethylcyclopropyl (TMCP) moiety, but also CYP1A2 and CYP2C19 showed activity. Inhibition of CYP3A4 in HLM attenuated the metabolism of UR‐144 and XLR‐11, while inhibition of the other CYP enzymes in HLM had only minor effects. Thus, CYP3A4 is the major contributor to the CYP mediated metabolism of UR‐144 and XLR‐11 with minor contributions from CYP1A2. Users of UR‐144 and XLR‐11 are thus subject to the influence of potential drug‐drug interactions, if they are concomitantly medicated with CYP3A4 inducers (e.g. some antiepileptics) or inhibitors (e.g. some antifungal drugs). Copyright © 2015 John Wiley & Sons, Ltd.
Powerful Antibacterial Activity of Phenyl‐Thiolatobismuth(III) Complexes Derived from Oxadiazolethiones
Authors: Luqman Ahmad , Blair Victoria L. , Brammananth Rajini , Crellin Paul K. , Coppel Ross L. , Andrews Philip C.
Published: September 2015

Seven novel 5‐substituted phenylthiazole oxadiazolethiones: [Me‐PTOT(H)], [MeO‐PTOT(H)], [MeS‐PTOT(H)], [F‐PTOT(H)], [Cl‐PTOT(H)], [Br‐PTOT(H)], and [CF3‐PTOT(H)], {where X‐PTOT(H) = 5‐[2‐(4‐X)thiazol‐4‐yl]‐1,3,4‐oxadiazole‐2(3H)‐thione, 4‐X = C6H4}, were synthesised from their corresponding thioamides. From these seven heteroleptic thiolatobismuth complexes: BiPh(Me‐PTOT)2 6, BiPh(MeO‐PTOT)2 7, BiPh(MeS‐PTOT)2 8, BiPh(F‐PTOT)2 9, BiPh(Cl‐PTOT)2 10, BiPh(Br‐PTOT)2 11 and BiPh(CF3‐PTOT)2 12 were synthesised and characterised. Complexes [10(DMSO)2] and [11(DMSO)2] were structurally characterised using X‐ray diffraction. Evaluation of the antibacterial properties of the thiones and their BiIII complexes against Mycobacterium smegmatis, Staphylococcus aureus (S. aureus), Methicillin‐resistant Staphylococcus aureus (MRSA), Vancomycin‐resistant Enterococcus (VRE), Enterococcus faecalis (E. faecalis) and Escherichia coli (E. coli) showed that all bismuth(III) complexes were highly effective against all the bacteria, as demonstrated by very low MIC values (1.1–2.1 μM). Complexes BiPh(Me‐PTOT)2 6, BiPh(Cl‐PTOT)2 10 and BiPh(Br‐PTOT)2 11, showed best activity against the multi‐drug resistant bacteria VRE and MRSA with an MIC value of 1.0 μM. All these complexes and their corresponding thiones failed to show any prominent activity against M. smegmatis and E. coli, even at high concentrations. These complexes showed little or no toxicity towards mammalian COS‐7 cells at 20 μg/mL.