bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of cell culture medium additives on color and acidic charge variants of a monoclonal antibody
Authors: Vijayasankaran Natarajan , Varma Sharat , Yang Yi , Meier Steven , Kiss Robert
Published: June 2018

This manuscript summarizes the effect of certain cell culture medium additives on antibody drug substance coloration and acidic charge variants. It has been shown previously that B‐vitamins and iron in the cell culture medium could significantly impact color intensity. In this manuscript, we detail the effect of several other cell culture components that have been shown to impact coloration. It is shown that if cystine is used instead of cysteine in the cell culture medium, coloration was reduced. Hydrocortisone has been shown to reduce coloration and boost specific productivity. The effect of a peptone/hydrolysate on coloration was investigated in cell culture experiments, which showed its use can lead to reduced coloration. Mechanisms by which these compounds influence coloration will be briefly discussed. Since it has been previously shown that antibody oxidation could potentially lead to coloration, the current effort was focused on screening for specific antioxidant additives to the culture medium to reduce coloration. An in‐vitro incubation model was used to screen antioxidant compounds, several of which were found to significantly reduce antibody color, while some led to significantly increased color. Hypotaurine and carboxymethylcysteine, which had the most significant color reducing effect in the incubation study, were further tested in small‐scale bioreactor cell culture experiments. These studies demonstrated that these compounds lead to reduced coloration in cell culture without affecting cell growth and titer. Hypotaurine, hydrocortisone, peptone, and cystine were also shown to reduce the acidic charge variant levels, which was previously shown to correlate with color. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018 © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1298–1307, 2018
Extending the Applicability of Exact Nuclear Overhauser Enhancements to Large Proteins and RNA
Authors: Nichols Parker J. , Born Alexandra , Henen Morkos A. , Strotz Dean , Celestine Chi N. , Güntert Peter , Vögeli Beat
Published: June 2018

Distance‐dependent nuclear Overhauser enhancements (NOEs) are one of the most popular and important experimental restraints for calculating NMR structures. Despite this, they are mostly employed as semiquantitative upper distance bounds, and this discards the wealth of information that is encoded in the cross‐relaxation rate constant. Information that is lost includes exact distances between protons and dynamics that occur on the sub‐millisecond timescale. Our recently introduced exact measurement of the NOE (eNOE) requires little additional experimental effort relative to other NMR observables. So far, we have used eNOEs to calculate multistate ensembles of proteins up to approximately 150 residues. Here, we briefly revisit eNOE methodology and present two new directions for the use of eNOEs: applications to large proteins and RNA.
Chromium Complexes with Oxido and Corrolato Ligands: Metal‐Based Redox Processes versus Ligand Non‐Innocence
Authors: Garai Antara , Sobottka Sebastian , Schepper Rahel , Sinha Woormileela , Bauer Matthias , Sarkar Biprajit , Kar Sanjib
Published: June 2018

Metal‐ versus ligand‐centered redox processes and the effects of substituents on the ligands on the spectroscopic properties of the metal complexes are at the heart of research on metal complexes with non‐innocent ligands. This work presents three examples of chromium complexes that contain both oxido and corrolato ligands, with the substituents on the corrolato ligands being different in the three cases. Combined X‐ray crystallographic, electrochemical, UV/Vis/NIR/EPR spectroelectrochemical, and EXAFS/XANES measurements, together with DFT calculations, have been used to probe the complexes in three different redox forms. This combined approach makes it possible to address questions related to chromium‐ versus corrolato‐centered redox processes, and the accessibility (or not) of CrIV, CrV, and CrVI in these complexes, as well as their spin states. To the best of our knowledge, these are the first EXAFS/XANES investigations on Cr‐corrolato complexes in different redox forms, and hence these data should set benchmarks for future investigations on such complexes by this method.
Direct Amination of Alcohols Catalyzed by Aluminum Triflate: An Experimental and Computational Study
Authors: Payard Pierre‐Adrien , Gu Qingyi , Guo Wenping , Wang Qianran , Corbet Matthieu , Michel Carine , Sautet Philippe , Grimaud Laurence , Wischert Raphael , Pera‐Titus Marc
Published: June 2018

Among the best‐performing homogeneous catalysts for the direct amination of activated secondary alcohols with electron‐poor amine derivatives, metal triflates, such as aluminum triflate, Al(OTf)3, stand out. Herein we report the extension of this reaction to electron‐rich amines and activated primary alcohols. We provide detailed insight into the structure and reactivity of the catalyst under working conditions in both nitromethane and toluene solvent, through experiment (cyclic voltammetry, conductimetry, NMR spectroscopy), and density functional theory (DFT) simulations. Competition between aniline and benzyl alcohol for Al in the two solvents explains the different reactivities. The catalyst structures predicted from the DFT calculations were validated by the experiments. Whereas a SN1‐type mechanism was found to be active in nitromethane, we propose a SN2 mechanism in toluene to rationalize the much higher selectivity observed when using this solvent. Also, unlike what is commonly assumed in homogeneous catalysis, we show that different active species may be active instead of only one.
Phenothiazine‐Based Oligo(p‐phenylenevinylene)s: Substituents Affected Self‐Assembly, Optical Properties, and Morphology‐Induced Transport
Authors: Arivazhagan C. , Satapathy Sitakanta , Jana Arijit , Malakar Partha , Prasad Edamana , Ghosh Sundargopal
Published: June 2018

Designing intramolecular charge‐transfer (ICT)‐based luminogenic ordered assemblies exhibiting significant electrical transport is a challenging task in the field of organic optoelectronics. In this context, a series of novel phenothiazine‐based oligo(p‐phenylenevinylene) (OPV1‐6) derivatives were designed and their structure–property relationship was investigated. Upon examining their photophysical properties, all the OPVs were found to exhibit significant intramolecular charge‐transfer characteristics in organic solvents. While inspecting the self‐assembly behaviour, the OPV with a long alkyl chain on the central phenyl core (OPV4) underwent gelation in organic solvent mixtures through strong hydrophobic interactions of the long hexadecyl chains and π‐interactions from their aromatic counterparts. Computational studies revealed a lamellar packing of molecules in the assembly. Interestingly, the degree of ICT and the gelation abilities of OPVs were significantly influenced by the electronic nature of the substituents appended to the peripheral phenothiazines. Further, the AC impedance results revealed an increase in storage and electronic transport for the fluorescent thin films prepared by an increase in the content of OPV4 in PMMA.
In Silico Design and Enantioselective Synthesis of Functionalized Monocyclic 3‐Amino‐1‐carboxymethyl‐β‐lactams as Inhibitors of Penicillin‐Binding Proteins of Resistant Bacteria
Authors: Decuyper Lena , Deketelaere Sari , Vanparys Lore , Jukič Marko , Sosič Izidor , Sauvage Eric , Amoroso Ana Maria , Verlaine Olivier , Joris Bernard , Gobec Stanislav , D'hooghe Matthias
Published: June 2018

As a complement to the renowned bicyclic β‐lactam antibiotics, monocyclic analogues provide a breath of fresh air in the battle against resistant bacteria. In that framework, the present study discloses the in silico design and unprecedented ten‐step synthesis of eleven nocardicin‐like enantiomerically pure 2‐{3‐[2‐(2‐aminothiazol‐4‐yl)‐2‐(methoxyimino)acetamido]‐2‐oxoazetidin‐1‐yl}acetic acids starting from serine as a readily accessible precursor. The capability of this novel class of monocyclic 3‐amino‐β‐lactams to inhibit penicillin‐binding proteins (PBPs) of various (resistant) bacteria was assessed, revealing the potential of α‐benzylidenecarboxylates as interesting leads in the pursuit of novel PBP inhibitors. No deactivation by representative enzymes belonging to the four β‐lactamase classes was observed, while weak inhibition of class C β‐lactamase P99 was demonstrated.
Deactivation of Excited States in Transition‐Metal Complexes: Insight from Computational Chemistry
Authors: Sousa Carmen , Alías Marc , Domingo Alex , de Graaf Coen
Published: June 2018

Investigation of the excited‐state decay dynamics of transition‐metal systems is a crucial step for the development of photoswitchable molecular based materials with applications in growing fields as energy conversion, data storage, or molecular devices. The photophysics of these systems is an entangled problem arising from the interplay of electronic and geometrical rearrangements that take place on a short time scale. Several factors play a role in the process: various electronic states of different spin and chemical character are involved, the system undergoes important structural variations and several nonradiative processes can occur. Computational chemistry is a useful tool to get insight into the microscopic description of the photophysics of these materials, since it provides unique information about the character of the electronic spin states involved, the energetics and time evolution of the system. In this review article, we present an overview of the state of the art methodologies available to address the several aspects that have to be incorporated to properly describe the deactivation of excited states in transition‐metal complexes. The most recent developments in theoretical methods are discussed and illustrated with examples.
Benzylic Functionalisation of Phenyl all‐cis‐2,3,5,6‐Tetrafluorocyclohexane Provides Access to New Organofluorine Building Blocks
Authors: Bykova Tetiana , Al‐Maharik Nawaf , Slawin Alexandra M. Z. , Bühl Michael , Lebl Tomas , O'Hagan David
Published: June 2018

Selectively fluorinated hydrocarbons continue to attract attention for tuning pharmacokinetic properties in agrochemical and pharmaceutical discovery programmes. This study identifies benzylic bromination of phenyl all‐cis‐2,3,5,6‐tetrafluorocyclohexane 2 as a key reaction for accessing building blocks containing the all‐cis‐2,3,5,6‐tetrafluorocyclohexane ring system. These cyclohexanes are of interest as the fluorines are only on one face of the cyclohexane, and this imparts an unusual polar aspect, very different to an otherwise hydrophobic cyclohexane. Ritter type reactions of benzyl bromide 4 with DMF and acetonitrile generated the corresponding benzyl alcohol 6 and benzylacetamide 7 respectively. Benzylacetamide 7 was hydrolysed to benzyl amine 8 and syn‐amino‐alcohol 9, and separately the phenyl ring was oxidatively cleaved to furnish carboxylic acid acetamide 10, which after hydrolysis gave the tetrafluorocyclohexyl amino acid 11. A trans‐halogenation of benzylbromide 4 with AgF2 gave benzyl fluoride 13. Oxidative cleavage of the aryl ring then gave pentafluorocyclohexyl carboxylic acid 14. This carboxylic acid was readily converted to amides 23–26 and the preferred conformations of these α‐fluoroamides were explored by DFT, X‐ray structure and 1H–19F HOESY NMR analysis.
Donor–Acceptor Complexes between 1,2,5‐Chalcogenadiazoles (Te, Se, S) and the Pseudohalides CN−and XCN−(X=O, S, Se, Te)
Authors: Semenov Nikolay A. , Gorbunov Dmitry E. , Shakhova Margarita V. , Salnikov Georgy E. , Bagryanskaya Irina Y. , Korolev Valery V. , Beckmann Jens , Gritsan Nina P. , Zibarev Andrey V.
Published: June 2018

Donor–acceptor (D–A) complexes between 3,4‐dicyano‐1,2,5‐chalcogenadiazoles [chalcogen=Te (1 a), Se (1 b), S (1 c)] and the pseudohalides CN−and XCN−(X=O, S, Se, Te) were studied experimentally and theoretically. For1 a, they were isolated as [K(18‐crown‐6)][1 a‐CN] (2), [K(18‐crown‐6)][1 a‐NCO] (3), [K(18‐crown‐6)][1 a‐SCN] (4), [K(18‐crown‐6)][1 a‐SeCN] (5), and [K][1 a‐NCSe] (6) and characterized by X‐ray diffraction (XRD), UV/Vis and NMR spectroscopy, and DFT and QTAIM calculations. For1 band1 c, the complexes were not isolated due to unfavorable thermodynamics. In all isolated complexes, the D–A bonds, stabilized by negative hyperconjugation, were longer than the sum of the covalent radii and shorter than the sum of the van der Waals radii of the bonded atoms. In mixtures of1 a, F−, and SeCN−, the complex [1 a‐F]−was selectively formed in accordance with thermodynamics. The reaction of1 awith SeCN−and the cyclic trimeric perfluoro‐ortho‐phenylene mercury afforded the complex [K(18‐crown‐6)][SCN]⋅(o‐C6F4Hg)3, which was characterized by XRD.
Hydrogen Bonding of N‐Heterocyclic Carbenes in Solution: Mechanisms of Solvent Reorganization
Authors: Gehrke Sascha , Hollóczki Oldamur
Published: June 2018

The hydrogen‐bond dynamics of N‐heterocyclic carbenes plays a central role in their proton‐transfer reactions, and the effects of hydrogen bonding are also often invoked in corresponding organocatalytic applications. In the present study, the structures and lifetimes of hydrogen bonds have been investigated for several carbenes in alcohol‐containing solutions by classical molecular dynamics simulations. The basicity of the carbene was found to be of major importance; while the least basic carbenes are often in their free form in the solvent, by increasing the basicity the simulations show increased hydrogen bonding, often even with two alcohol molecules at a time. In the latter structure the single lone pair of the carbene is in interplay with two hydrogen bond donors. The exchange mechanism is different for carbenes with different basicities, with different substituents, and in different solvents, occurring through the free carbene for the least basic compounds, and through the aforementioned doubly‐hydrogen‐bonded structure in case of the most basic derivatives. Since this process plays a central role also in H/D exchange reactions, we argue that the pK values calculated from the related measurements have a varying physical meaning for the different carbenes. The lifetimes of the hydrogen bonds are apparently also clearly related to the basicity of the carbene, with gradually increasing lifetimes for the most basic compounds.
Diversity Driven Decoration and Ligation of Fullerene by Ugi and Passerini Multicomponent Reactions
Authors: Ravanello Bruno B. , Seixas Nalin , Rodrigues Oscar E. D. , da Silva Rafael S. , Villetti Marcos A. , Frolov Andrej , Rivera Daniel G. , Westermann Bernhard
Published: June 2018

Aiming at providing an efficient and versatile method for the diversity‐oriented decoration and ligation of fullerenes, we report the first C60 derivatization strategy based on isocyanide‐multicomponent reactions (I‐MCRs). The approach comprises the use of Passerini and Ugi reactions for assembling pseudo‐peptidic scaffolds (i.e., N‐alkylated and depsipeptides, peptoids) on carboxylic acid‐functionalized fullerenes. The method showed wide substrate scope for the oxo and isocyanide components, albeit the Ugi reaction proved efficient only for aromatic amines. The approach was successfully employed for the ligation of oligopeptides and polyethyleneglycol chains (PEG) to C60, as well as for the construction of bis‐antennary as well as PEG‐tethered dimeric fullerenes. The quantum yields for the formation of 1O2 was remarkable for the selected compounds analyzed.
A Porous Framework as a Variable Chemosensor: From the Response of a Specific Carcinogenic Alkyl‐Aromatic to Selective Detection of Explosive Nitroaromatics
Authors: Xue Hui , Song Danhua , Liu Caiping , Lyu Guangxun , Yuan Daqiang , Jiang Feilong , Chen Qihui , Hong Maochun
Published: June 2018

Selective probing of one molecule from one class of similar molecules is highly challenging due to their similar chemical and physical properties. Herein, a novel metal–organic framework FJI‐H15 with flexible porous cages has been designed and synthesized, which can specifically recognize ethylbenzene with ultrahigh enhancement efficiency from a series of alkyl‐aromatics, in which an unusual size‐dependent interaction has been found and proved. It can also selectively detect phenolic‐nitroaromatics among a series of nitroaromatics based on energy transfer and electrostatic interactions. Such unusual specificity and variable mechanisms responding to different types of molecules have not yet been reported, which will provide a new strategy for the development of more effective chemosensors based on MOFs for probing small structural differences in molecules.
Reaction Kinetics Direct a Rational Synthesis of an HIV‐1 Inactivator of Nucleocapsid Protein 7 and Provide Mechanistic Insight into Cellular Metabolism and Antiviral Activity
Authors: Nikolayevskiy Herman , Scerba Michael T. , Deschamps Jeffrey R. , Appella Daniel H.
Published: June 2018

Invited for the cover of this issue is the group of Daniel Appella at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. The image depicts the critical role of both oxidative and acetylative mechanistic pathways as the thiolate of SAMT‐247 attempts to hold the viral particle at bay. Read the full text of the article at 10.1002/chem.201801253.
Novel Oxidative Ugi Reaction for the Synthesis of Highly Active, Visible‐Light, Imide‐Acridinium Organophotocatalysts
Authors: Gini Andrea , Uygur Mustafa , Rigotti Thomas , Alemán José , García Mancheño Olga
Published: June 2018

A newly designed class of acridinium‐based organophotocatalysts bearing an imide group at the C9‐position is presented. To achieve these unprecedented structures, a synthetic strategy based on a novel straightforward oxidative Ugi‐type reaction at the benzylic position of C9‐unsubstituted acridanes was developed. The introduction of the imide‐unit affords a notable photocatalytic activity enhancement, allowing efficient transformations in different oxidative and reductive visible‐light catalytic reactions.
OCT1 Deficiency Affects Hepatocellular Concentrations and Pharmacokinetics of Cycloguanil, the Active Metabolite of the Antimalarial Drug Proguanil
Authors: Matthaei Johannes , Seitz Tina , Jensen Ole , Tann Annabelle , Prukop Thomas , Tadjerpisheh Sina , Brockmöller Jürgen , Tzvetkov Mladen V.
Published: June 2018

Cycloguanil, the active metabolite of proguanil, acts on malaria schizonts in erythrocytes and hepatocytes. We analyzed the impact of the organic cation transporter OCT1 on hepatocellular uptake and pharmacokinetics of proguanil and cycloguanil. OCT1 transported both proguanil and cycloguanil. Common variants OCT1*3 and OCT1*4 caused a substantial decrease and OCT1*5 and OCT1*6 complete abolishment of proguanil uptake. In 39 healthy subjects, low‐activity variants OCT1*3 and OCT1*4 had only minor effects on proguanil pharmacokinetics. However, both, cycloguanil area under the time‐concentration curve and the cycloguanil‐to‐proguanil ratio were significantly dependent on number of these low‐functional alleles (P = 0.02 for both). Together, CYP2C19, CYP3A5, OCT1 polymorphisms, and sex accounted for 61% of the variation in the cycloguanil‐to‐proguanil ratio. Most importantly, in vitro OCT1 inhibition caused a fivefold decrease of intracellular cycloguanil concentrations in primary human hepatocytes. In conclusion, OCT1‐mediated uptake is a limiting step in bioactivation of proguanil, and OCT1 polymorphisms may affect proguanil efficacy against hepatic malaria schizonts.
“…Not Intended to Diagnose, Treat, Cure or Prevent Any Disease.” 25 Years of Botanical Dietary Supplement Research and the Lessons Learned
Authors: Gurley Bill J. , Yates Charles R. , Markowitz John S.
Published: June 2018

Botanical dietary supplements (BDS) are complex mixtures of phytochemicals exhibiting complex pharmacology and posing complex research challenges. For 25 years, clinical pharmacologists researching BDS have confronted a litany of issues unlike those encountered with conventional medications. Foundational to these concerns is the Dietary Supplement Health and Education Act of 1994, which exempted BDS from premarket safety and efficacy trials. In the ensuing period, safety concerns regarding multi‐ingredient products formulated as “proprietary blends” and herb‐drug interactions have garnered significant attention. Idiosyncrasies unique to BDS can affect the outcome and interpretation of in vitro and in vivo studies, and although “omics” approaches hold promise in uncovering BDS efficacy mechanisms, purposeful adulteration threatens their safety. Despite a quarter century of public use, healthcare professionals still know little about BDS, thus it falls to industry, government, and academia to join forces in promoting a new paradigm for BDS research and product development.
CYP2D6 Genotype Phenotype Discordance Due to Drug‐Drug Interaction
Authors: Monte Andrew A. , West Kelsey , McDaniel Kyle T. , Flaten Hania K. , Saben Jessica , Shelton Shelby , Abdelmawla Farah , Bushman Lane R. , Williamson Kayla , Abbott Diana , Anderson Peter L.
Published: June 2018

Drug‐drug interactions have been demonstrated to alter cytochrome 2D6 (CYP2D6) enzyme phenotype due to inhibitor ingestion, although it is unclear how substrate interactions affect phenotype. This was a pragmatic clinical trial examining the kinetics of a CYP2D6 enzyme probe drug with and without CYP2D6‐dependent substrates. Patients were enrolled into an inpatient study unit, and orally administered a 2 mg microdose of dextromethorphan (DM) to probe enzyme activity with and without CYP2D6‐dependent drug‐drug interactions. Thirty‐nine subjects were enrolled in this trial. Twelve subjects were on no CYP2D6‐dependent drugs and 27 were on one or more CYP2D6‐dependent drugs. There were 1 poor metabolizer, 5 intermediate metabolizers, 31 normal metabolizers, and 2 ultra‐rapid metabolizers. Those with co‐ingestion of another CYP2D6‐dependent drug were 9.49 (95% confidence interval (CI): 1.54–186.41; P = 0.01) times more likely to have genotype‐phenotype discordance based upon the 3 hours dextrophan/dextromethorphan (DX/DM) ratio. CYP2D6 substrate co‐ingestions can cause genotype‐phenotype discordance.
Electrochemically Deposited Nickel Oxide from Molecular Complexes for Efficient Water Oxidation Catalysis
Authors: Tong Lianpeng , Wu Wenling , Kuepper Karsten , Scheurer Andreas , Meyer Karsten
Published: June 2018

A facile method for the electrodeposition of amorphous nickel oxyhydroxide is described and discussed in which well‐defined nickel complexes with pyridinedimethanol ligands are employed as single‐source molecular precursors. No buffering agent is required to assist the anodic deposition process. The deposited nickel oxyhydroxide shows high robustness and efficiency for electrocatalytic water oxidation.
Gouty tophi presenting as multinodular lateral inguinal swelling: A case report
Authors: Goel Nidhi , Khanna Venus , Jain Dileep Kumar , Gupta Vivek
Published: June 2018

Fine‐needle aspiration cytology (FNAC) is an important diagnostic tool which is replacing biopsy for the diagnosis of subcutaneous nodules. We present a case of 75 years old female with right sided multinodular lateral inguinal swelling since 2 years, without any clinical features of arthritis. FNAC of the lesion revealed negatively birefringent, long needle shaped monosodium urate crystals in the background of amorphous granular debris. Further investigations revealed high serum uric acid levels (9.36 mg/dL) and a confirmed diagnosis of gouty tophus was made. It is important that pathologist should be aware of the cytological features of gouty tophus, particularly in the case with unusual presentation. Gouty nodulosis has never been reported in literature at this site and we are first to report gouty tophus at this unique site.
Diagnosis of paraganglioma as a pancreatic mass: A case report
Authors: Nguyen Elise , Nakasaki Manando , Lee Thomas K. , Lu Di
Published: June 2018

Paragangliomas are rare neoplasms that arise from the chromaffin cells of the autonomic nervous system. Although paragangliomas can occur anywhere paraganglia are present, they tend to occur in the head, neck, and retroperitoneum. Rarely, paragangliomas can occur in the peripancreatic area and present as a pancreatic mass, creating a diagnostic challenge for the clinician, radiologist, and pathologist. Here, we present a case of a 70‐year‐old woman with history of breast carcinoma who presented with chronic constipation, early satiety, and an abdominal mass. Her first abdominal CT described a 3.6 cm × 5 cm × 4.5 cm cystic and solid mass involving the pancreatic tail that was suspicious for a pancreatic neoplasm. A subsequent abdominal CT described a 5.9 cm multilobulated solid and cystic lesion close to the pancreatic tail. Endoscopic ultrasound‐guided fine‐needle aspirate of the mass demonstrated scant to moderate cellularity of a heterogeneous population of atypical cells, some with epithelioid morphology and others appearing neuroendocrine‐like. By morphology and immunohistochemical stains, an extra‐adrenal paraganglioma or pheochromocytoma was considered as a possible diagnosis. The surgical resection specimen confirmed the diagnosis of paraganglioma. This case demonstrates the importance of awareness of paragangliomas in the differential diagnosis of a fine‐needle aspiration of a pancreatic mass to avoid erroneous diagnosis.
The Pivotal Role of Ru‐dmso Compounds in the Discovery of Well‐Behaved Precursors
Authors: Bratsos Ioannis , Alessio Enzo
Published: June 2018

This paper is a tribute to the rich chemistry and great versatility of ruthenium‐dmso precursors: over the years, from a handful of complexes we prepared literally hundreds of derivatives with all types of ligands, from mono‐ to polydentate, from pure σ‐donors (e.g. NH3) to phosphines and strong π‐acceptors such as CO and NO. This systematic and extensive investigation had a thread of thought running through it: the identification of compounds that might have functional roles, either because they possess peculiar physical‐chemical properties or because they undergo predictable and stereo‐controlled substitution reactions, that is, they are well‐behaved precursors. From a more fundamental point of view, this systematic investigation led us to get a deeper understanding of the subtle differences in the soft nature of ruthenium and osmium, as well as in the delicate balance between electronic and steric preferences of the dmso ligand and of its remarkable adaptability to the coordination environment.
Organic Synthesis without Conventional Solvents
Authors: Obst Martin , König Burkhard
Published: June 2018

Organic synthesis without an organic solvent is still the exception. In this microreview, we discuss and compare different synthetic methods that proceed in the absence of conventional organic solvents. This includes solvent‐free methods in solids (mechanochemistry and solid‐state photochemistry), and in neat liquids (thermal and photocatalytic), as well as the application of unconventional solvents, such as ionic liquids and deep‐eutectic solvents. The different approaches are briefly introduced and examples illustrate their specific advantages, followed by a critical discussion of their limitations. Some methods have the intrinsic benefits of solvent‐free operation, such as avoiding solubility problems and side‐reactions with the solvent. However, every method has specific advantages and the demand of the synthetic application is crucial for selecting the best technique.
The long‐term evolution of the Doruneh Fault region (Central Iran): A key to understanding the spatio‐temporal tectonic evolution in the hinterland of the Zagros convergence zone
Authors: Tadayon Meisam , Rossetti Federico , Zattin Massimiliano , Calzolari Gabriele , Nozaem Reza , Salvini Francesco , Faccenna Claudio , Khodabakhshi Pouria
Published: June 2018

A better understanding of intraplate deformation requires the knowledge of the space–time scales involved in its development and to decipher possible links with the dynamic evolution of the plate boundaries. Central Iran provides an ideal test site to approach this scientific issue, since it is characterised by a prolonged history of Mesozoic–Cenozoic intraplate deformation that has been interfering with the spatio‐temporal re‐organization of the Zagros convergence zone along the Eurasia plate boundary. This study focus on the Doruneh Fault (DF) region that is considered as the northern mechanical boundary of the Central East Iranian Microcontinent. By combining field investigations with apatite low‐temperature thermochronology, we present a revised tectono‐stratigraphic scenario for the DF region, typified by a punctuated history of fault‐related exhumation, burial and cooling history back to the Upper Cretaceous. When framed at regional scale, these results attest that the Zagros convergence zone, and its hinterland domain were fully mechanically coupled since ca. 40–35 Ma, a time lapse that is here referred as to the onset of continental collision along the Arabia–Eurasia plate boundary. In this scenario, the DF region operated throughout the Cenozoic as a major zone of residual stress accommodation and transfer in the hinterland domain of the Zagros convergence zone. Results of this study also suggest that the tectonic evolution along the Arabia–Eurasia plate boundary was modulated by the plate‐boundary dynamics and by the modes of tectonic reactivation of the intracontinental weak zones of Central Iran and at its tectonic boundaries.
Mississippian lithofacies and foraminiferal biozonation of the Alborz Mountains, Iran: Implications for regional geology
Authors: Zandkarimi Keyvan , Vachard Daniel , Najafian Bahram , Mosaddegh Hossein , Ehteshami‐Moinabadi Mohsen
Published: June 2018

The Mississippian rocks at 5 sections, Kalariz, Peyghambaran, Jaban, Naserabad, and Dozdehban, have been measured and sampled in a SE–NW direction across the Alborz Mountains. Foraminiferal zones recognized in those sections, as well as a revision of other foraminiferal assemblage previously published from the Alborz Mountains, allow to recognize 12 biozones: 5 in the Tournaisian: Unilocular (MFZ1–MFZ2? interval), Septabrunsiina krainica (MFZ3–MFZ5 interval), Eotextularia diversa (MFZ6), Darjella monilis (MFZ7), and primitive Eoparastaffella (MFZ8); 5 Viséan biozones: Eoparastaffella simplex (MFZ9), primitive archaediscids (MFZ10), Uralodiscus rotundus (MFZ11), Pojarkovella–Koskinotextularia (MFZ12), Neoarchaediscus (Upper Mikhailovian), Howchinia gibba–Archaediscus/Paraarchaediscus at angulatus‐tenuis stage–Neoarchaediscus akchimensis (Venevian substage); and 2 Serpukhovian biozones: Biseriella parva–Climacammina (Tarusian–Steshevian substages) and Turrispiroides multivolutus–Brenckleina–Eostaffellina protvae (Protvian substage) for the Mississippian rocks of Alborz. Analysis of foraminiferal assemblages indicates a noticeable age difference of the Mississippian rocks between the northern and southern flanks of Alborz. Accordingly, south‐eastern and east‐central Alborz (Kalariz, Peyghambaran, and Jaban sections) display complete Tournaisian deposits (MFZ1–MFZ8), whereas northern Alborz contains the strata dated from Late Tournaisian to Late Serpukhovian (MFZ8–MFZ16). The sedimentological studies also reveal sharp facies variations following the mentioned age variation. Previously, the age variations of these rocks were attributed to various events, such as the Mississippian glaciation phases. However, the age, facies, and thickness variations of lithostratigraphic units in the Alborz are not specific to the Mississippian and are reported during the entire Palaeozoic and even Mesozoic and Cenozoic. They can rather be attributed to the inherited basement and syn‐sedimentary E–W‐trending faults.
New basal synapsid discovery at the Permian outcrop of Torre del Porticciolo (Alghero, Italy)
Authors: Romano Marco , Citton Paolo , Maganuco Simone , Sacchi Eva , Caratelli Martina , Ronchi Ausonio , Nicosia Umberto
Published: June 2018

The Torre del Porticciolo fossil locality is notable for producing the first osteological material of a basal (i.e., non‐mammalian) synapsid in Italy, the giant herbivore Alierasaurus ronchii, which although known from fragmentary remains, likely represents the largest known late early to early middle Permian synapsid (6–7 m total length). Recently, a new productive site was discovered about 100 m from the Alierasaurus type locality, but roughly at the same stratigraphic level. The fragmentary nature of most of the recovered bones prompted a taphonomical analysis in order to define the type of find, the kind of burial, and the mode of preservation. The vertebrate remains allowed us to infer a complex taphonomical process involving a multiphase entombment. The recovered bones were subjected to both re‐exhumation and reworking. The last short and violent transportation phase before final entombment occurred as a high‐energy flow, probably caused by a river flood that carried sediment and bones together to be emplaced in a semi‐perennial pond in a crevasse splay deposit. Preliminary analysis of recovered material indicates the presence of a large carnivorous basal synapsid referable to the family Sphenacodontidae. This discovery represents the first carnivorous non‐therapsid synapsid from the Permian of Italy and one of only very few known from Europe.
Altered brain activation and connectivity during anticipation of uncertain threat in trait anxiety
Authors: Geng Haiyang , Wang Yi , Gu Ruolei , Luo Yue‐Jia , Xu Pengfei , Huang Yuxia , Li Xuebing
Published: June 2018

In the research field of anxiety, previous studies generally focus on emotional responses following threat. A recent model of anxiety proposes that altered anticipation prior to uncertain threat is related with the development of anxiety. Behavioral findings have built the relationship between anxiety and distinct anticipatory processes including attention, estimation of threat, and emotional responses. However, few studies have characterized the brain organization underlying anticipation of uncertain threat and its role in anxiety. In the present study, we used an emotional anticipation paradigm with functional magnetic resonance imaging (fMRI) to examine the aforementioned topics by employing brain activation and general psychophysiological interactions (gPPI) analysis. In the activation analysis, we found that high trait anxious individuals showed significantly increased activation in the thalamus, middle temporal gyrus (MTG), and dorsomedial prefrontal cortex (dmPFC), as well as decreased activation in the precuneus, during anticipation of uncertain threat compared to the certain condition. In the gPPI analysis, the key regions including the amygdala, dmPFC, and precuneus showed altered connections with distributed brain areas including the ventromedial prefrontal cortex (vmPFC), dorsolateral prefrontal cortex (dlPFC), inferior parietal sulcus (IPS), insula, para‐hippocampus gyrus (PHA), thalamus, and MTG involved in anticipation of uncertain threat in anxious individuals. Taken together, our findings indicate that during the anticipation of uncertain threat, anxious individuals showed altered activations and functional connectivity in widely distributed brain areas, which may be critical for abnormal perception, estimation, and emotion reactions during the anticipation of uncertain threat.
R‐THP‐COP versus R‐CHOP in patients younger than 70 years with untreated diffuse large B cell lymphoma: A randomized, open‐label, noninferiority phase 3 trial
Authors: Hara Takeshi , Yoshikawa Takeshi , Goto Hideko , Sawada Michio , Yamada Toshiki , Fukuno Kenji , Kasahara Senji , Shibata Yuhei , Matsumoto Takuro , Mabuchi Ryoko , Nakamura Nobuhiko , Nakamura Hiroshi , Ninomiya Soranobu , Kitagawa Junichi , Kanemura Nobuhiro , Nannya Yasuhito , Katsumura Naoki , Takahashi Takeshi , Kito Yusuke , Takami Tsuyoshi , Miyazaki Tatsuhiko , Takeuchi Tamotsu , Shimizu Masahito , Tsurumi Hisashi
Published: June 2018

Pirarubicin (tetrahydropyranyl adriamycin [THP]) is an anthracyclin with less cardiotoxicity than doxorubicin (DOX). We previously reported the efficacy and safety of R‐THP‐COP consisting of rituximab (R), THP, cyclophosphamide (CPA), vincristine (VCR), and prednisolone (PSL) for diffuse large B cell lymphoma (DLBCL) in phase 2 studies. Here, we prospectively compared the efficacy and safety of the R‐THP‐COP and standard R‐CHOP regimen (consisting of R, CPA, DOX, VCR, and PSL) in a noninferiority phase 3 trial. This prospective, randomized phase 3 study included patients younger than 70 years of age with previously untreated DLBCL. The regimen consisted of R (day 1), DOX, or THP (day 3), CPA (day 3), VCR (day 3), and PSL for 5 days every 3 weeks for 6 to 8 cycles. Between July 5, 2006 and June 11, 2013, 81 patients were randomly assigned to the treatment groups (R‐CHOP group, 40 patients; R‐THP‐COP group, 41 patients). R‐THP‐COP was noninferior to R‐CHOP, as assessed by the primary endpoint of complete response rate (85% vs 85% respectively). With a median follow‐up of 75.2 months, the 5‐year overall survival was 87% in the R‐CHOP group and 82% in the R‐THP‐COP group (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.31‐2.49; P = .82). The 5‐year progression‐free survival was 74% in the R‐CHOP group and 79% in the R‐THP‐COP group (HR: 1.37, 95% CI: 0.56‐3.55; P = .49). No grade 3 cardiac side effects were observed in either group. No serious late adverse reactions were observed in either group, with the exception of therapy‐related acute myeloid leukemia in the R‐THP‐COP group. These data indicate that R‐THP‐COP is noninferior to R‐CHOP with regard to clinical response, and has an acceptable safety profile. Thus, this regimen may be an alternative therapy to R‐CHOP.
Inside Cover: Light sheet microscopy and SrAl2O4 nanoparticles codoped with Eu2+/Dy3+ ions for cancer cell tagging (J. Biophotonics 6/2018)
Authors: Can‐Uc Bonifacio , Montes‐Frausto Juana B. , Juarez‐Moreno Karla , Licea‐Rodriguez Jacob , Rocha‐Mendoza Israel , Hirata Gustavo A.
Published: June 2018

Optically‐sectioned image of a single MCF‐7 cancer cell taken under light‐sheet microscopy. Green color corresponds to the persistent luminescence signal, from internalized FA‐SrAl2O4: Eu2+, Dy3+ nanoparticles (NPs) through folate receptors, indicating the cytoplasmic localization. Blue color corresponds to DAPI fluorescence signal from the cell nucleus. The NPs and cell preparations were conducted at CNyN‐UNAM. The imaging was conducted at the Advanced Optical Microscopy Laboratory of CICESE.

Further details can be found in the article by Bonifacio Can‐Uc et al. (e201700301).

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Two gastroenteritis outbreaks caused by sapovirus in Shenzhen, China
Authors: Wang MD Jinjin , Li PhD Yuan , Kong MD Xiangxu , Li PhD Huiying , Zhang BA Qing , Jin PhD Miao , Wang PhD Yongjie , Duan PhD Zhaojun
Published: June 2018

Human sapoviruses (SaVs) are a common cause of the acute gastroenteritis epidemic worldwide, and SaV outbreaks and infections have become more frequent in recent years. Since the end of December, 2015 to December, 2016, 2 gastroenteritis outbreaks occurred in 2 kindergarten classes (outbreaks A and B) in the Baoan district, Shenzhen, China. Feces and swabs were collected for laboratory tests of causative agents, and no bacterial pathogens were detected. Both the outbreaks were positive for SaV with a detection rate of 75% of symptomatic cases (6/8) in outbreak A and 71% (10/14) in outbreak B. For outbreak B, 1 of 3 asymptomatic teachers was detected to be SaV positive. The genome of some of the strains in this study was obtained, and the strains from outbreak A were genotyped into GII.3, while those from outbreak B were genotyped into GI.2, according to the phylogenetic analysis of the polymerase and the capsid region. No recombination was identified in either the GII.3 or GI.2 strain. GI.2 strains experience chronological variation, and the GI.2 strain in this study belonged to the most recent variant, which was observed from 2008 to 2016. The variation mainly occurred in the P domain from 1990 to 2016. Meanwhile, GII.3 strains shared greater similarity (>98.2%) at the amino acid identities; from 1999 to 2015, only 5 of them were in the predicted P domain. Our results suggest that it is necessary to conduct routine SaV surveillance and molecular characterization to further understand the SaV epidemic.
An efficient modeling of series‐parallel structure for the digital downconversion of pulsar signals in astronomical observation system
Authors: Wan Guo Chun , Liu Wen Jing , Zhang Ying Qian , Tong Mei Song
Published: June 2018

This paper proposes an efficient modeling of series‐parallel structure for the digital downconversion (DDC) implemented in the field programmable gate array for astronomical observation system. The received signals by a radio telescope are of intermediate frequency, and they can be stored and analyzed only after having been converted into digital baseband signals. Although many algorithms have been proposed for the traditional DDC, it is still hard to balance the working frequency of signals and the hardware resources of field programmable gate array. The proposed series‐parallel structure can not only solve the problem but also provide a more compact size, lower consumption of power, and transplanting ability for the DDC module. The new structure has been used for the signal processing of pulsars in an astronomical observation system, and those merits have been validated.
Polarization‐resolved Raman modes of monoclinic SrAl2O4 ceramics
Authors: Dias Anderson , Moreira Roberto Luiz
Published: June 2018

SrAl2O4 materials were obtained by molten salt synthesis and sintered at high temperatures to produce a ceramic body suitable for polarization‐resolved Raman spectroscopy measurements. Optimized experimental conditions were employed to study the complex vibrational spectrum of these ceramics under polarized light. A reliable set of experimental bands was obtained: 69 Raman modes were in fact observed, out of the 81 bands foreseen for the stable monoclinic polymorph of the material, from which 38 could be assigned as totally symmetric A‐type modes, and 31 attributed as asymmetric B‐type ones. Significant differences between experimental data and theoretical predictions indicated that additional efforts are necessary to understand these two sets of vibrational information. The knowledge of the optical phonon features reported here can help to understand the exceptional luminescence properties of SrAl2O4 in its monoclinic phase.
Raman spectroscopy as a powerful technique for the identification of polymers used in cast sculptures from museum collections
Authors: Klisińska‐Kopacz Anna , Łydżba‐Kopczyńska Barbara , Czarnecka Monika , Koźlecki Tomasz , del Hoyo Mélendez Julio , Mendys Agata , Kłosowska‐Klechowska Anna , Obarzanowski Michał , Frączek Piotr
Published: June 2018

The chemical identification of materials is the first step for developing and implementing recommendations for the care and display of resin cast and plastic objects in museum collections. This paper presents advantages as well as limitations of portable Raman. Therefore, a comparative analysis of portable and benchtop Raman instruments was performed in the study of materials found in the contemporary art collections of the National Museum in Krakow. The results of the Raman study were complemented with those obtained using Fourier transform infrared, near infra‐red, and gas chromatography mass spectrometry, in order to verify their accuracy. The results of this study showed that portable Raman spectroscopy is a suitable technique for the identification plastics in museum collections.
Land‐use change structures carnivore communities in remaining tallgrass prairie
Authors: Wait Kyle R. , Ricketts Andrew M. , Ahlers Adam A.
Published: June 2018

The Flint Hills ecoregion is the largest remaining tract of native tallgrass prairie in North America. Contemporary landscape change (e.g., urbanization, agricultural production) in this region is likely affecting native biodiversity; however, we have a limited understanding of how these changes might affect carnivores. We used camera traps distributed across urban‐rural land‐use gradients, and multiseason occupancy models, to investigate the influence of landscape structure and composition on habitat occupancy dynamics of 3 native carnivores (coyote [Canis latrans]; bobcat [Lynx rufus]; and striped skunk [Mephitis mephitis]) and 1 nonnative carnivore (domestic cat) in the Flint Hills, Kansas, USA, during 2016–2017. Additionally, we assessed the potential for coyotes, the apex predator in the Flint Hills, to mediate habitat occupancy of domestic cats. We also examined the relative influence of landscape factors on native carnivore species richness and diversity. As predicted, coyotes were less likely to occupy and colonize sites, and more likely to leave sites, surrounded by urban landcover. Habitat occupancy by bobcats was positively associated with forest landcover and edge densities; however, bobcats seemed insensitive to urban landcover. Additionally, bobcats were more likely to colonize sites with more grassland and row‐crop agriculture landcover. Surprisingly, striped skunk occupancy and colonization rates at sites were negatively related to urban landcover. As expected, domestic cats were more likely to occur at and colonize sites with increased urban landcover and less likely at sites with high coyote occupancy probabilities. Carnivore species diversity and richness were negatively related to the urban landcover. Our results suggest that urban landcover may limit the spatial distributions of some native carnivores in the Flint Hills and contribute to reduced carnivore diversity. Moreover, urban landcover in the Flint Hills may provide domestic cats with refugia from intraguild pressures by coyotes. Our results provide wildlife managers with insights into how contemporary landscape change in this imperiled ecosystem may affect biodiversity conservation and maintenance. © 2018 The Wildlife Society.