bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolomics in patients with psychosis: A systematic review
Authors: Li Christopher , Wang Aviva , Wang Chloe , Ramamurthy Janani , Zhang Edlyn , Guadagno Elena , Trakadis Yannis
Published: August 2018

The purpose of this article is to provide a comprehensive review of metabolomics studies for psychosis, as a means of biomarker discovery. Manuscripts were selected for review if they involved discovery of metabolites using high‐throughput analysis in human subjects and were published in the last decade. The metabolites identified were searched in Human Metabolome Data Base (HMDB) for a link to psychosis. Metabolites associated with psychosis based on evidence in HMBD were then searched using PubMed to explore the availability of further evidence. Almost all of the studies which underwent full review involved patients with schizophrenia. Ten biomarkers were identified. Six of them were reported in two or more independent metabolomics studies: N‐acetyl aspartate, lactate, tryptophan, kynurenine, glutamate, and creatine. Four additional metabolites were encountered in a single metabolomics study but had significant evidence (two supporting articles or more) for a link to psychosis based on PubMed: linoleic acid, D‐serine, glutathione, and 3‐hydroxybutyrate. The pathways affected are discussed as they may be relevant to the pathophysiology of psychosis, and specifically of schizophrenia, as well as, constitute new drug targets for treatment of related conditions. Based on the biomarkers identified, early diagnosis of schizophrenia and/or monitoring may be possible.
A rare exonic NRXN3 deletion segregating with neurodevelopmental and neuropsychiatric conditions in a three‐generation Chinese family
Authors: Yuan Haiming , Wang Qingming , Liu Yanhui , Yang Wei , He Yi , Gusella James F. , Song Jiage , Shen Yiping
Published: August 2018

Members of the neurexin gene family, neurexin 1 (NRXN1), neurexin 2 (NRXN2), and neurexin 3 (NRXN3) encode important components of synaptic function implicated in autism and other neurodevelopmental/neuropsychiatric disorders. Loss of function variants have been reported predominantly in NRXN1, with fewer such variants detected in NRXN2 and NRXN3. Evidence for segregating NRNX3 variants has particularly been lacking. Here, we report identification by chromosomal microarray analysis of a rare exonic deletion affecting the NRXN3 alpha isoform in a three‐generation Chinese family. The proband, a 7‐year‐old boy, presented with motor and language delay and met the clinical diagnostic criteria for autism. He also presented with moderate intellectual disability, attention‐deficit hyperactivity disorder and facial dysmorphic features. The mother and maternal grandfather, both deletion carriers, presented with variable degrees of language and communication difficulties, as well as neuropsychiatric problems such as schizophrenia and temper tantrums. A compilation of sporadic cases with deletions involving part or all of NRXN3 revealed that 9 of 23 individuals (39%) displayed features of autism. The evidence for cosegregation in our family further supports a role for NRXN3 in autism and neurodevelopmental/neuropsychiatric disorders but demonstrates intrafamily variable expressivity due to this NRXN3 deletion, with schizophrenia and facial dysmorphism being potential novel features of NRXN3 haploinsufficiency.
Direkter Zugang zu Azulenen über eine Gold‐katalysierte Dimerisierung von Diarylalkinen
Authors: Claus Vanessa , Schukin Michael , Harrer Siegfried , Rudolph Matthias , Rominger Frank , Asiri Abdullah M. , Xie Jin , Hashmi A. Stephen K.
Published: August 2018

Eine einfache Gold‐katalysierte Methode für die Synthese von substituierten und modifizierbaren Azulenen wurde entwickelt. Die Azulene werden entweder über die Dimerisierung von Push‐Pull‐Diarylalkinen mit Fluor‐Substituenten in ortho‐ oder para‐Position, oder über die Dimerisierung eines symmetrischen elektronenreichen Diarylalkins gebildet. In Anwesenheit eines kationischen Gold‐Katalysators bilden die zwei Alkine ein hoch reaktives Vinyl‐Kation. Diese energiereiche Zwischenstufe wird durch eine passende Aryl‐Einheit abgefangen, sodass liefert in einem einzigen, perfekt atomökonomischen Schritt substituierte Azulene erhalten werden.
Applications of Selenonium Cations as Lewis Acids in Organocatalytic Reactions
Authors: He Xinxin , Wang Xinyan , Tse Ying‐Lung (Steve) , Ke Zhihai , Yeung Ying‐Yeung
Published: August 2018

The use of trisubstituted selenonium salts as organic Lewis acids in electrophilic halogenation and aldol‐type reactions has been developed. The substrate scope is broad. The reaction conditions are mild and compatible with various functionalities. This study opens a new avenue for the development of nonmetallic Lewis acid catalysis.
Nitrogen‐Doped Graphene Quantum Dots Enhance the Activity of Bi2O3 Nanosheets for Electrochemical Reduction of CO2 in a Wide Negative Potential Region
Authors: Chen Zhipeng , Mou Kaiwen , Wang Xiaohan , Liu Licheng
Published: August 2018

Large numbers of catalysts have been developed for the electrochemical reduction of CO2 to value‐added liquid fuels. However, it remains a challenge to maintain a high current efficiency in a wide negative potential range for achieving a high production rate of the target products. Herein, we report a 2D/0D composite catalyst composed of bismuth oxide nanosheets and nitrogen‐doped graphene quantum dots (Bi2O3‐NGQDs) for highly efficient electrochemical reduction of CO2 to formate. Bi2O3‐NGQDs demonstrates a nearly 100 % formate Faraday efficiency (FE) at a moderate overpotential of 0.7 V with a good stability. Strikingly, Bi2O3‐NGQDs exhibit a high activity (average formate FE of 95.6 %) from −0.9 V to −1.2 V vs. RHE. Additionally, DFT calculations reveal that the origin of enhanced activity in this wide negative potential range can be attributed to the increased adsorption energy of CO2(ads) and OCHO* intermediate after combination with NGQDs.
A Polyimide Nanolayer as a Metal‐Free and Durable Organic Electrode Toward Highly Efficient Oxygen Evolution
Authors: Lin Yun‐Xiao , Feng Wei‐Jie , Zhang Jun‐Jun , Xue Zhong‐Hua , Zhao Tian‐Jian , Su Hui , Hirano Shin‐Ichi , Li Xin‐Hao , Chen Jie‐Sheng
Published: August 2018

The exploitation of metal‐free organic polymers as electrodes for water splitting reactions is limited by their presumably low activity and poor stability, especially for the oxygen evolution reaction (OER) under more critical conditions. Now, the thickness of a cheap and robust polymer, poly(p‐phenylene pyromellitimide) (PPPI) was rationally engineered by an in situ polymerization method to make the metal‐free polymer available for the first time as flexible, tailorable, efficient, and ultra‐stable electrodes for water oxidation over a wide pH range. The PPPI electrode with an optimized thickness of about 200 nm provided a current density of 32.8 mA cm−2 at an overpotential of 510 mV in 0.1 mol L−1 KOH, which is even higher than that (31.5 mA cm−2) of commercial IrO2 OER catalyst. The PPPI electrodes are scalable and stable, maintaining 92 % of its activity after a 48‐h chronoamperometric stability test.
The Chemical Sciences and Equality, Diversity, and Inclusion
Authors: Mehta Goverdhan , Yam Vivian W. W. , Krief Alain , Hopf Henning , Matlin Stephen A.
Published: August 2018

There has been mounting concern over the absence of gender equality in the sciences in recent years. This has been accompanied by a broadening of the perspective, in order to address issues of equality, diversity and inclusion, relating to a wide range of circumstances in which individuals suffer discrimination. While some progress has been made in some countries, nationally or at the level of institutions, much more needs to be done. The chemical sciences can play a leading role in addressing biases, through 1) becoming a model of good systemic practice in policies, processes, and actions; 2) developing practical skills through training in cultural competence; and 3) promoting a stronger evidence base to uncover both the extent of problems and the degree to which approaches to improve equality, diversity, and inclusion are working.
Gold‐Catalyzed Dimerization of Diarylalkynes: Direct Access to Azulenes
Authors: Claus Vanessa , Schukin Michael , Harrer Siegfried , Rudolph Matthias , Rominger Frank , Asiri Abdullah M. , Xie Jin , Hashmi A. Stephen K.
Published: August 2018

We have developed a simple gold‐catalyzed procedure for the synthesis of substituted and modifiable azulenes. The azulenes are formed either by the dimerization of push–pull diarylalkynes bearing a fluorine atom in ortho or para position or by the dimerization of a symmetric electron‐rich diarylalkyne. In the presence of a cationic gold catalyst, the two alkynes can form a highly reactive vinyl cation. Trapping of this high‐energy intermediate by an appropriate aryl unit then delivers substituted azulenes in a single step and in a perfect atom economy.
A General Approach to Site‐Specific, Intramolecular C−H Functionalization Using Dithiocarbamates
Authors: Na Christina G. , Alexanian Erik J.
Published: August 2018

Intramolecular hydrogen atom transfer is an established approach for the site‐specific functionalization of unactivated, aliphatic C−H bonds. Transformations using this strategy typically require unstable intermediates formed using strong oxidants and have mainly targeted C−H halogenations or intramolecular aminations. Herein, we report a site‐specific C−H functionalization that significantly increases the synthetic scope and convergency of reactions proceeding via intramolecular hydrogen atom transfer. Stable, isolable N‐dithiocarbamates are used as precursors to amidyl radicals formed via either light or radical initiation to efficiently deliver highly versatile alkyl dithiocarbamates across a wide range of complex structures.
Efficient Synthesis of (−)‐Corynoline by Enantioselective Palladium‐Catalyzed α‐Arylation with Sterically Hindered Substrates
Authors: Rao Xiaofeng , Li Naikai , Bai Heng , Dai Chaodi , Wang Zheng , Tang Wenjun
Published: August 2018

Sterically hindered substrates can be employed in an enantioselective palladium‐catalyzed α‐arylation with the chiral monophosphorus ligand BI‐DIME. This process enabled an efficient synthesis of the antidepressant (S)‐nafenodone, a four‐step enantioselective synthesis of the Sceletium alkaloid (+)‐sceletium A‐4, a concise five‐step enantioselective synthesis of (−)‐corynoline, as well as a three‐step preparation of (−)‐DeN‐corynoline.
Dramatically Enhanced Solubility of Halide‐Containing Organometallic Species in Diiodomethane: The Role of Solvent⋅⋅⋅Complex Halogen Bonding
Authors: Kinzhalov Mikhail A. , Kashina Mariya V. , Mikherdov Alexander S. , Mozheeva Ekaterina A. , Novikov Alexander S. , Smirnov Andrey S. , Ivanov Daniil M. , Kryukova Mariya A. , Ivanov Aleksandr Yu. , Smirnov Sergej N. , Kukushkin Vadim Yu. , Luzyanin Konstantin V.
Published: August 2018

In the current study, we evaluated the solubility of a number of organometallic species and showed that it is noticeably improved in diiodomethane when compared to other haloalkane solvents. The better solvation properties of CH2I2 were associated with the substantially better σ‐hole‐donating ability of this solvent, which results in the formation of uniquely strong solvent–(metal complex) halogen bonding. The strength of the halogen bonding is attenuated by the introduction of additional halogen atoms in the organometallic species owing to the competitive formation of more favourable intermolecular complex–complex halogen bonding. The exceptional solvation properties of diiodomethane and its inertness towards organometallic species make this solvent a good candidate for NMR studies, in particular, for the acquisition of spectra of insensitive spins.
Local Activities of Hydroxide and Water Determine the Operation of Silver‐Based Oxygen Depolarized Cathodes
Authors: Botz Alexander , Clausmeyer Jan , Öhl Denis , Tarnev Tsvetan , Franzen David , Turek Thomas , Schuhmann Wolfgang
Published: August 2018

Local ion activity changes in close proximity to the surface of an oxygen depolarized cathode (ODC) were measured by scanning electrochemical microscopy (SECM). While the operating ODC produces OH− ions and consumes O2 and H2O through the electrocatalytic oxygen reduction reaction (ORR), local changes in the activity of OH− ions and H2O are detected by means of a positioned Pt microelectrode serving as an SECM tip. Sensing at the Pt tip is based on the pH‐dependent reduction of PtO and obviates the need for prior electrode modification steps. It can be used to evaluate the coordination numbers of OH− ions and H2O, and the method was exploited as a novel approach of catalyst activity assessment. We show that the electrochemical reaction on highly active catalysts can have a drastic influence on the reaction environment.
Thermodynamically Stable, Photoreversible Pharmacology in Neurons with One‐ and Two‐Photon Excitation
Authors: Passlick Stefan , Richers Matthew T. , Ellis‐Davies Graham C. R.
Published: August 2018

Photoswitchable bioprobes enable bidirectional control of cell physiology with different wavelengths of light. Many current photoswitches use cytotoxic UV light and are limited by the need for constant illumination owing to thermal relaxation in the dark. Now a photoswitchable tetrafluoroazobenzene(4FAB)‐based ion channel antagonist has been developed that can be efficiently isomerized in two separate optical channels with visible light. Importantly, the metastable cis configuration showed very high stability in the dark over the course of days at room temperature. In neurons, the 4FAB antagonist reversibly blocks voltage‐gated ion channels with violet and green light. Furthermore, photoswitching could also be achieved with two‐photon excitation yielding high spatial resolution. 4FAB probes have the potential to enable long‐term biological studies where both ON and OFF states can be maintained in the absence of irradiation.
Enantio‐ and Diastereoselective Synthesis of Chiral Allenes by Palladium‐Catalyzed Asymmetric [3+2] Cycloaddition Reactions
Authors: Trost Barry M. , Zell Daniel , Hohn Christoph , Mata Guillaume , Maruniak Autumn
Published: August 2018

A protocol for the asymmetric synthesis of highly substituted chiral allenes with control of point and axial chirality has been developed. A palladium‐catalyzed [3+2] cycloaddition using readily available racemic allenes gives access to densely functionalized chiral allenes with excellent yields and functional group tolerance. The catalytic asymmetric protocol utilizes a broad range of allenyl TMM (trimethylenemethane) donors to form cyclopentanes, pyrrolidines, and spirocycles with very good control of regio‐, enantio‐, and diastereoselectivity. The chiral allene moiety is shown to be a valuable functional group for rapid elaboration towards complex targets.
Moving Toward an Evidence‐based Family and Community‐based Approach to Improve the Lives of Children and Young People Who Have Experienced Abuse and Neglect
Authors: Heriot Sandra , Kissouri Maria
Published: August 2018

The Their Futures Matter reform is the New South Wales (NSW) Government's coordinated approach and long‐term strategy for how we support vulnerable children and families. In 2016, funding was provided to implement two evidence‐based models – Multisystemic Therapy for Child Abuse and Neglect (MST‐CAN®) and Functional Family Therapy – Child Welfare (FFTCW®). Both models target the causes of harm and respond to trauma and other underlying causes of child abuse and neglect. They are delivered by teams of practitioners in the family home and community (a departure from the way most interventions are normally delivered), and provide intensive home‐based services aimed at keeping families together. To span the gap between science and practice in the delivery of MST‐CAN® and FFT‐CW®, implementation is supported through a partnership between government and intermediaries supporting service providers. With the guidance of a New York (NY)‐based organisation, The New York Foundling, these intermediaries apply the Community Development Team model, an implementation strategy that uses an evidence‐based implementation approach to introduce treatment models that are themselves informed by evidence, which helps increase the likelihood of sustained treatment success. Experience across the globe, however, indicates that investment in evidence‐based approaches is not enough to secure successful outcomes for families and communities. The NSW Government is also investing in other measures aimed at addressing a range of common implementation barriers such as staff training and retention, identification of suitable families, and cultural competence. The latter is critical given the over‐representation of Aboriginal children and young people in child protection and the out‐of‐home‐care system. Over a three‐year period, evidence will be collected of this investment's impact on child and family outcomes, and on implementation support. This paper will discuss how the partnership processes of working more flexibly with service providers, families, and communities can lead to enhanced outcomes.
Enhancement of soot oxidation activity of manganese oxide (Mn2O3) through doping by the formation of Mn1.9M0.1O3–δ (M = Co, Cu, and Ni)
Authors: Neelapala Satya Deepika , Patnaik Harsh , Dasari Harshini
Published: August 2018

The current work describes the catalytic soot oxidation activity of metal‐doped manganese oxide (Mn1.9M0.1O3–δ; M = Co, Cu, and Ni) materials, synthesized by coprecipitation method. All the fabricated materials were characterized using X‐ray diffraction (XRD), field emission scanning electron microscopy (FESEM), Brunauer–Emmett–Teller surface area analysis, and X‐ray photoelectron spectroscopy (XPS). XRD analysis confirmed the formation of solid solution Mn1.9M0.1O3–δ (M = Co, Cu, and Ni). M‐doped samples exhibited different morphology when compared with pure Mn2O3 as evidenced by FESEM analysis, and Co‐doped Mn2O3 possessed the highest specific surface area. XPS analysis revealed the presence of multiple oxidation states of Mn (+4, +3, and +2) and Co (+2 and +3). Soot oxidation activity tests, performed using thermogravimetric analysis, showed that Mn1.9Co0.1O3–δ exhibited better catalytic performance (T50 = 390°C) when compared with pure Mn2O3 (T50 = 490°C). The incorporation of dopants greatly enhanced the oxygen vacancies and redox properties of Mn2O3.
Molecular self‐assembly and morphology induction in high‐performance aromatic phosphonated block copolymers
Authors: Kumar Avneesh , Pisula Wojciech , Müllen Klaus
Published: August 2018

Well‐defined morphology induction in new block copolymers based on high‐performance individual blocks is presented here. Rod‐ and coil‐like polymers such as poly(phenylene oxide) and poly(vinybenzyl phosphonic acid), respectively, contribute to the origin of self‐assembly via phase separation between chemically dissimilar regions. Individual blocks of homopolymer are oriented in a cooperative manner leading to a controlled stacking of macromolecules and evolution of microspheres with a size up to 200 nm in solution. Growth of ordered phase in poly(p‐phenylene oxide) chains are recorded as a result of molecular reorganization guided by poly(vinybenzyl phosphonic acid) segment. The stacking of macromolecules is noticed under atomic force microscope. Influence of the size of poly(phenylene oxide) block on self‐assembly is also examined. Scattering patterns from two‐dimensional wide angle X‐ray scattering verifies the crystalline domains in copolymers. Further end to end and side by side orientations of macromolecules are confirmed by X‐ray experiments. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46750.
Development of starch‐furcellaran‐gelatin films containing tea tree essential oil
Authors: Jamróz Ewelina , Juszczak Lesław , Kucharek Mateusz
Published: August 2018

Tea tree essential oil (TEO) was added in different concentrations (2%, 4%, and 6%) to starch/furcellaran/gelatin (S/F/G) films. Film solubility of S/F/G film significantly decreased when containing 6% TEO (P ≤ 0.05). Referring to the control sample (without TEO), water content decreased with increasing concentration of oil. Films with 4% and 6% TEO exhibited a significant decrease (P ≤ 0.05) in tensile strength, and Young's modulus. The amounts of TEO had no significant on the elongation at break (P ≤ 0.05). Analysis obtained by Fourier transform infrared spectroscopy exhibited some insights on the possible interactions between polysaccharides, protein, and essential oil. The thermal stability of the film was decreased by TEO addition. The antioxidant properties proved to be significantly enhanced with addition of TEO into films. S/F/G films incorporated with TEO showed antimicrobial activity against Staphylococcus aureus and Escherichia coli, with inhibition zone diameters of 27.8 ± 0.29 mm and 18.4 ± 0.20 mm, respectively. Our results suggested that the S/F/G films containing TEO could be used as an active film which enhances microbial safety and the shelf‐life of foods due to its good in vitro antioxidant and antimicrobial properties for food packaging applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46754.
Porous aromatic networks with amine linkers for adsorption of hydroxylated aromatic hydrocarbons
Authors: Li Q. , Mu X. , Xiao S. , Wang C. , Chen Y. , Yuan X.
Published: August 2018

The porous covalent organic polymers (COPs) are valuable materials in various fields such as gas storage, adsorption or separation, luminescent detection, catalysis, and sensors. Two thermally stable COPs with aromatic skeleton linked by amine groups were prepared by Buchwald–Hartwig protocol. The COPs with respective Brunauer–Emmett–Teller surface area of 204 and 178 m2/g were employed for adsorption of hydroxylated aromatic hydrocarbons (HAHs) due to expected strong π–π stacking and hydrogen‐bond interactions between COPs and HAH. In adsorption of phenol from water, COP2 showed far better capacity than COP1, silica, basic alumina, and macroporous resin (D101). In adsorption of 2‐naphthol COP1 and COP2 displayed similar capacity, being 2.8, 5.4, and 7.4 times high as those for macroporous resin (D101), basic alumina, and silica, respectively. COP1 and COP2 are useful for efficient separation of 2‐naphthol or other HAHs from waste water. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 46919.
Enhanced ion conductivity of poly(ethylene oxide)‐based single ion conductors with lithium 1,2,3‐triazolate end groups
Authors: Hoffmann Justus Friedrich , Pulst Martin , Kressler Jörg
Published: August 2018

Poly(ethylene oxide) (PEO)‐based single ion conductors (SICs) are of great interest for applications in modern lithium ion batteries. They have several advantages over other common electrolytes such as high cation transference numbers, low toxicity, and nonflammability, but their major disadvantage is the low ion conductivity. Here, linear PEO‐based SICs with lithium 1,2,3‐triazolate (TrLi) end groups are synthesized and studied in terms of crystallinity by differential scanning calorimetry, and with respect to ion conductivity by impedance spectroscopy. Introduction of TrLi end groups to PEO chains reduces its crystallinity and melting temperature as well as an enhancement of the ion conductivity up to 8.0·10−6 S cm−1 at 70°C is observed. The increased ion conductivity is a direct result of the Tr rings, which can actively contribute to the conduction mechanism. In comparison with conductivities of other PEO‐based SICs reached so far (σ0 ≤ 10−6 S cm−1), the results of this study show that the introduction of TrLi end groups is a new approach to enhance the Li+‐ion conductivity of PEO‐based SICs that have also a good electrochemical stability versus lithium electrodes as revealed by linear sweep voltammetry. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 46949.
A biomimetic cellulose‐based composite material that incorporates the antimicrobial metal‐organic framework HKUST‐1
Authors: Rickhoff T. A. , Sullivan E. , Werth L. K. , Kissel D. S. , Keleher J. J.
Published: August 2018

The synthesis and characterization of a biomimetic composite material composed of cellulose acetate embedded with a copper‐based metal‐organic framework, MOF‐199 (HKUST‐1), is reported and has been investigated for use as an adsorbent material in water remediation. Incorporation of MOF‐199 into cellulose acetate enhances the stability of the metal‐organic framework in water allowing for a flexible and tunable polymeric material. The adsorption of methylene blue to the cellulose‐MOF199 composite was tracked spectroscopically over time and is best described by a mixed Langmuir–Freundlich isotherm adsorption model. The total remediation of methylene blue to the cellulose‐MOF199 composite is comparable to that of pure cellulose, however, it is shown herein that incorporation of MOF‐199 into cellulose acetate inhibits the growth of the Gram‐negative bacterium Escherichia coli. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 46978.
Ancient DNA and its contribution to understanding the human history of the Pacific Islands
Authors: BEDFORD STUART , BLUST ROBERT , BURLEY DAVID V. , COX MURRAY , KIRCH PATRICK V. , MATISOO‐SMITH ELIZABETH , NÆSS ÅSHILD , PAWLEY ANDREW , SAND CHRISTOPHE , SHEPPARD PETER
Published: August 2018

Two recent papers, by Lipson et al. and Posth et al., have challenged current interpretations of the initial settlement of Remote Oceania. We invited Stuart Bedford, who is an author on both papers, to outline their importance, and a number of scholars in various disciplines to comment on their findings.
Design and evaluation of biological activities of 1,3‐oxazolidinone derivatives bearing amide, sulfonamide, and thiourea moieties
Authors: Karaman Nurcan , Adil Zainel Rabeah , Kapkaç Handan A. , Karaca Gençer Hülya , Ilgın Sinem , Karaduman A. Burak , Karaküçük‐İyidoğan Ayşegül , Oruç‐Emre Emine E. , Koçyiğit‐Kaymakçıoğlu Bedia
Published: August 2018

1,3‐Oxazolidine‐2‐one is an important heterocyclic ring participating in the chemical structure of many drugs. In this research, 22 new amide/sulfonamide/thiourea derivatives (1–22) were obtained by the reaction of (S)‐4‐(4‐aminobenzyl)‐2(1H)‐1,3‐oxazolidinone with 4‐substituted benzoyl chlorides, 4‐substituted benzene sulfonyl chlorides, and 4‐substituted phenyl isothiocyanates. The structures of all synthesized compounds were clarified by FT‐IR, NMR, and mass spectroscopic and elemental analysis techniques. The synthesized compounds were screened for their antimicrobial activity. Antimicrobial susceptibility and cellular physiology were evaluated using the microbroth dilution assay and the flow cytometry method. As a result, it was determined that compound 16 displayed better antimicrobial activity than chloramphenicol against Gram‐positive bacteria, especially Staphylococcus aureus. In order to understand the mechanism of effect of the compounds on the cell membrane, fluorescence microscopy was used. Cell membrane damage of the Gram positive bacteria treated with compound 16 was observed as a result of intense staining with propidium iodide. In addition, genotoxicity, cytotoxicity, and absorption, distribution, metabolism, and excretion (ADME) parameters of compound 16 were examined and it was found as non‐mutagenic and non‐cytotoxic at the concentration at which it showed antimicrobial activity. According to the calculated ADME parameters and drug likeness scores, the compounds can be good drug candidates, especially compound 16.
Synthesis of novel sulfamides incorporating phenethylamines and determination of their inhibition profiles against some metabolic enzymes
Authors: Aksu Kadir , Akıncıoğlu Hülya , Akıncıoğlu Akın , Göksu Süleyman , Tümer Ferhan , Gülçin İlhami
Published: August 2018

A series of sulfamides were synthesized and evaluated for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carbonic anhydrase inhibition properties. The synthesis of sulfamides was achieved by the reactions of phenethylamines with N,N‐dimethylsulfamoyl chloride in the presence of Et3N. The methoxylated sulfamides were converted into their phenolic derivatives with BBr3 for structure–activity relationships. The synthesized sulfamide/phenolic sulfamide derivatives were investigated as cholinesterase inhibitors and their relative role in AChE versus BChE inhibition was defined. Sulfamide/phenolic sulfamide derivatives are known as important carbonic anhydrase inhibitors; therefore, the synthesized compounds were investigated for inhibitory effects on both carbonic anhydrase isoenzymes. Additionally, we evaluated four different enzymes, which were inhibited in the low nanomolar range by these compounds. According to the present studies, for AChE, BChE, and carbonic anhydrase I and II, the ranges of results are recorded as 0.027–0.076 nM, 0.075–0.327 nM, 0.123–0.678 nM, and 0.024–0.688 nM, respectively.
Efficacy and Safety of Febuxostat Extended and Immediate Release in Patients With Gout and Renal Impairment: A Phase III Placebo‐Controlled Study
Authors: Saag Kenneth G. , Becker Michael A. , Whelton Andrew , Hunt Barbara , Castillo Majin , Kisfalvi Krisztina , Gunawardhana Lhanoo
Published: August 2018

Objective

To assess the efficacy and safety of febuxostat extended release (XR) and immediate release (IR) in patients with gout and normal or impaired renal function.

Methods

This was a 3‐month, phase III, multicenter, double‐blind, placebo‐controlled study. Patients (n = 1,790) with a history of gout and normal or impaired (mild‐to‐severe) renal function were randomized to receive placebo, febuxostat IR 40 or 80 mg, or febuxostat XR 40 or 80 mg once daily (1:1:1:1:1 ratio). End points included proportions of patients with a serum urate (UA) level of <5.0 mg/dl at month 3 (primary end point), a serum UA level of <6.0 mg/dl at month 3, and ≥1 gout flare requiring treatment over 3 months (secondary end points).

Results

Both febuxostat formulations led to significantly greater proportions of patients achieving a serum UA level of <5.0 mg/dl or <6.0 mg/dl at month 3 (P < 0.001 for all comparisons versus placebo). Equivalent doses of febuxostat XR and IR had similar treatment effects on serum UA level end points; however, a significantly greater proportion of patients achieved a serum UA level of <5.0 mg/dl with XR 40 mg versus IR 40 mg. Similar proportions of patients experienced ≥1 gout flare across treatment groups. Rates of treatment‐emergent adverse events were low and evenly distributed between treatment arms. A preplanned subgroup analysis demonstrated that febuxostat formulations were well tolerated and generally effective on serum UA level end points (versus placebo) across all renal function subgroups.

Conclusion

Both formulations of febuxostat (XR and IR) were well tolerated and effective in patients with gout and normal or impaired renal function, including patients with severe renal impairment.
Asymmetric “Acetylenic” [3+2] Cycloaddition of Nitrones Catalyzed by Cationic Chiral PdII Lewis Acid
Authors: Honda Kazuya , Mikami Koichi
Published: August 2018

Highly enantioselective [3+2] cycloaddition of ynones and nitrones has been developed. Very bulky ligand, DTBM‐SEGPHOS, was used for an effective asymmetric induction over distal reaction centers on the linear ynone dipolarophile and for prevention of PdII catalyst deactivation by coordination of the nitrones. The reaction has wide scope of substrates in both ynones and nitrones.
Diruthenium Complexes of p‐Benzoquinone–Imidazole Hybrid Ligands: Innocent or Noninnocent Behavior of the Quinone Moiety
Authors: Ansari Mohd. Asif , Beyer Katharina , Schwederski Brigitte , Kaim Wolfgang , Lahiri Goutam Kumar
Published: August 2018

After double deprotonation, 2,6‐diaryl‐p‐benzoquinonodiimidazoles (aryl=4‐tolyl (I) or 2‐pyridyl (II)) were shown to bridge two [Ru(bpy)2]2+ (bpy=2,2′‐bipyridine) complex fragments through the imidazolate N and p‐quinone O (I→12+) or through the imidazolate N and pyridyl N donor atoms (II→22+). Characterization by crystal structure analysis, 1H/13C NMR spectroscopy, cyclic and differential pulse voltammetry, and spectroelectrochemistry (UV/Vis/NIR, IR, EPR) in combination with TD‐DFT calculations revealed surprisingly different electronic structures for redox systems 1n and 2n. Whereas 12+ is reduced to a radical complex with considerable semiquinone character, the reduction of 22+ with its exclusive N coordination exhibits little spin on the now redox‐innocent quinone moiety, compared with the electron uptake by the pyridyl–imidazolate chelating site. The first of two close‐lying oxidation processes occurs at the bridging heteroquinone ligand, whereas the second oxidation is partly (14+) or predominantly (24+) centered on the metal atoms.
Geometrically (Q, S, R)‐Incremental Dissipativity and Incremental Stability for Switched Time‐Varying Nonlinear Discrete‐Time Systems
Authors: Ren Yuanhong , Wang Weiqun , Wang Yixiang
Published: August 2018

This paper investigates geometrically (Q,S,R)‐incremental dissipativity and incremental stability for switched time‐varying nonlinear discrete‐time systems. A geometrically (Q,S,R)‐incremental dissipativity concept is proposed for switched nonlinear discrete‐time systems by using multiple storage functions and multiple incremental supply rate. Furthermore, the sufficient conditions of geometrically (Q,S,R)‐incremental dissipativity are given under the design of state‐dependent switching law. The incremental stability conditions are derived for geometrically (Q,S,R)‐incrementally dissipative switched systems. By designing of a composite state‐dependent switching law, the feedback interconnected switched systems are ensured to be geometrically (Q,S,R)‐incrementally dissipative. A numerical example is given to illustrate the validity of the proposed approach.
How will the onset and retreat of rainy season over East Asia change in future?
Authors: Kusunoki Shoji
Published: August 2018

Future change of the rainy season over East Asia region is investigated using the high horizontal resolution global atmospheric model called the Meteorological Research Institute‐Atmospheric General Circulation Model (MRI‐AGCM) version 3.2S (20‐km grid) and 3.2H (60 km). Higher reproducibility of precipitation during East Asian rainy season gives reliability of future projections. For the present‐day simulations (1983–2003, 21 years), the models are forced with observed historical sea surface temperature (SST). For the future simulations (1979–2099, 21 years), the models are forced with future SST projected by Atmosphere–Ocean General Circulation Models (AOGCMs) participated to the fifth phase of the Coupled Model Intercomparison Project (CMIP5). In order to estimate the uncertainty of future change, we execute ensemble simulations with three kinds of cumulus convection schemes and four kinds of SST distributions using 60‐km version to meet the limitation of computer resources. For each grid point, the onset and retreat of rainy season are defined from time evolution of pentad mean precipitation. The onset of rainy season becomes earlier in most regions over East Asia, but onset will delay in some area of western Japan. Retreat delays over China and Korea. Duration increases in most part of East Asia especially over China and Korea. This can be caused by enhanced water vapor transport from the tropics. The delay of onset over western Japan can be attributed to the decrease of water vapor transport associated with the southward shift of the subtropical high. Future change presented in higher horizontal resolution compared with previous studies is useful for impact, adaptation and mitigation studies of global warming.
Close linkage between quasi‐biweekly oscillation and tropical cyclone intensification over the western North Pacific
Authors: Zhou Haoyu , Hsu Pang‐Chi , Qian Yitian
Published: August 2018

Forecasting tropical cyclone (TC) intensity is challenging, particularly at the subseasonal scale. In this study, we found that compared to the 30−90‐day Madden–Julian oscillation (MJO), the activity of 10−30‐day quasi‐biweekly oscillation (QBWO) has a closer connection with the intensity change of TCs over the tropical western North Pacific. Both the TC growth rate (24‐hr increases in maximum sustained wind speed) and the probability of TC intensification during the active phases of QBWO increase significantly compared to those during the inactive QBWO phases. The effects of QBWO on TC intensification take place mainly through alteration of the large‐scale dynamic conditions. During the active convection phase of QBWO, the 10–30‐day cyclonic vorticity and convergence in the lower troposphere, divergence in the upper troposphere, and the circulation‐induced moistening anomalies provide a favorable environment for TC growth. The thermodynamic conditions of atmospheric instability, sea surface temperature (SST), and ocean heat potential show negative but insignificant contributions to TC intensification at the quasi‐biweekly time scale. These results not only aid our understanding of the influences of QBWO‐related environmental conditions on TC intensification, but also suggest the potential predictability of TC intensity at an extended range (10–30 days) once the QBWO has been successfully predicted.
Intensified impact of the central Pacific warming on the monsoon trough over the western North Pacific since 1984
Authors: Zhang Hongjie , Wu Liang , Huang Ronghui , Chen Jau‐Ming
Published: August 2018

The present study investigates the impact of the central Pacific warming (CPW) on the monsoon trough (MT) over the western North Pacific (WNP) during July–November of 1948–2015. It is shown that the relationship of the CPW with the MT experienced a remarkable change around 1984. Compared with 1948–1983, the MT was significantly stronger and extended eastward during the CPW events from 1984 to 2015. This relationship can be explained by the increase in the sea surface temperature (SST) in the tropical Pacific around 1984, especially over the central Pacific. Before 1984, the significantly cool ocean in the tropical western Pacific with the weakly warm ocean in the tropical central Pacific reduced the MT development and the eastward shift over the WNP during the CPW events. However, the enhanced low‐level westerlies and cyclonic vorticity induced by the warmer ocean surface in the tropical central Pacific led to the strengthening and further eastward extension of the MT during the CPW events after 1984. Following the eastward extension of the MT, the enhanced 850‐hPa positive vorticity, intensified 200‐hPa divergence, increased relative humidity, and reduced vertical wind shear tend to shift eastward during the CPW events after 1984, which favor tropical cyclone (TC) genesis. The results show more TCs after 1984 over the WNP during the CPW events than before 1984.
In vitro inhibition potential of mono‐n‐octyl phthalate on Mycobacterium tuberculosis H37Ra: Possibility of binding to mycobacterial PknB—An in silico approach
Authors: Rajiniraja Muniyan , Sivaramakrishna Akella , Sabareesh Varatharajan , Jayaraman Gurunathan
Published: August 2018

Fatty acids of specific chain lengths have been shown to inhibit the growth of Mycobacterium tuberculosis. In the present study, specific synthetic aromatic derivatives of n‐octyl esters were investigated for their property to inhibit the growth of M. tuberculosis H37Ra. Agar well diffusion assay indicated that the crude synthetic derivatives obtained by the esterification of phthalic acid (PA) and n‐octanol exhibited antimycobacterial activity. Further, the activity was authenticated with the Miroplate Alamar Blue Assay (MABA). Subsequently, the active component was purified by bioactivity guided chromatographic fractionation. The structure of the synthetic derivative was deduced by UV–Vis, FT‐IR, LC–MS, GC–mass spectrometry, and NMR spectroscopy. Molecular docking and molecular dynamic simulation (MDS) were performed with Autodock 4.0 and GROMACS 5.1.2 softwares, respectively. It was found that mono‐n‐octyl phthalate (MOP) exhibited antimycobacterial activity with a MIC of 20 μg/mL, and not by any other related compounds, including di‐n‐octyl phthalate, PA, phthalic anhydride, and n‐octanol. Binding of MOP with protein kinase B can participate in the binding cavity region, which was previously reported. Subsequently, we authenticate the stability with MDS. This is first report on the inhibition of M. tuberculosis growth by MOP.
Simulation and comparison of processes for biobutanol production from lignocellulose via ABE fermentation
Authors: Haigh Kathleen F. , Petersen Abdul M. , Gottumukkala Lalitha , Mandegari Mohsen , Naleli Karabo , Görgens Johann F.
Published: August 2018

Six conceptual process scenarios for the production of biobutanol from lignocellulosic biomass through acetone‐butanol‐ethanol (ABE) fermentation, using reported data on process performances, were developed with ASPEN Plus® V8.2 software. The six scenarios covered three fermentation strategies, i.e. batch separate hydrolysis and fermentation (SHF), continuous SHF, and batch simultaneous saccharification and fermentation (SSF) integrated with gas stripping (GS). The two downstream processing options considered were double‐effect distillation (DD) and liquid‐liquid extraction and distillation (LLE&D). It was found that the SSF‐GS/DD scenario was the most energy efficient with a liquid fuel efficiency of 24% and an overall efficiency of 31%. This was also the scenario with the best economic outcome, with an internal rate of return (IRR) of 15% and net present value (NPV) of US$387 million. The SSF‐GS/DD scenario was compared to a similar molasses process, based on the product flow rates, and it was found that the molasses process was more energy efficient with a gross energy value (GEV) of 23 MJ kg1 butanol compared to −117 MJ kg1 butanol for the lignocellulosic process. In addition, the molasses‐based process was more profitable with an IRR of 36% compared to 21%. However, the energy requirements for the molasses process were supplied from fossil fuels, whereas for the lignocellulose processes a portion of the feedstock was diverted to provide process energy. Improved environmental performance is therefore associated with the lignocellulosic process. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd
Three‐dimensional printing and virtual surgery for congenital heart procedural planning
Authors: Moore Ryan A. , Riggs Kyle W. , Kourtidou Soultana , Schneider Kristen , Szugye Nicholas , Troja Weston , D'Souza Gavin , Rattan Mantosh , Bryant Roosevelt , Taylor Michael D. , Morales David L.S.
Published: August 2018

Complex unrepaired congenital heart disease requires extensive planning to determine the optimal procedural approach. Conventional noninvasive diagnostic imaging initially provides only two‐dimensional (2D) representations of the complex, three‐dimensional cardiovascular anatomy. With the expansion of 3D visualization techniques in imaging, a paradigm shift has occurred in complex congenital heart disease surgical planning using digital and 3D printed heart models. There has been early success in demonstrating the benefit of these models in interdisciplinary communication and education. The future goal of this work is to demonstrate a clinical outcome benefit using digital and 3D printed models to plan both surgical and catheterization‐based interventional procedures. Ultimately, the hope is that advanced procedural planning with virtual surgery and 3D printing will enhance decision‐making in complex congenital heart disease cases resulting in improved perioperative performance by reducing operative times, complications, and reoperations.
Muscular Dystrophy Surveillance, Tracking, and Research Network pilot: Population‐based surveillance of major muscular dystrophies at four U.S. sites, 2007–2011
Authors: Do ThuyQuynh N. , Street Natalie , Donnelly Jennifer , Adams Melissa M. , Cunniff Christopher , Fox Deborah J. , Weinert Richard O. , Oleszek Joyce , Romitti Paul A. , Westfield Christina P. , Bolen Julie ,   on behalf of the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)
Published: August 2018

Background

For 10 years, the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) conducted surveillance for Duchenne and Becker muscular dystrophy (DBMD). We piloted expanding surveillance to other MDs that vary in severity, onset, and sources of care.

Methods

Our retrospective surveillance included individuals diagnosed with one of nine eligible MDs before or during the study period (January 2007–December 2011), one or more health encounters, and residence in one of four U.S. sites (Arizona, Colorado, Iowa, or western New York) at any time within the study period. We developed case definitions, surveillance protocols, and software applications for medical record abstraction, clinical review, and data pooling. Potential cases were identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) codes 359.0, 359.1, and 359.21 and International Classification of Diseases, Tenth Revision (ICD‐10) codes G71.0 and G71.1. Descriptive statistics were compared by MD type. Percentage of MD cases identified by each ICD‐9‐CM code was calculated.

Results

Of 2,862 cases, 32.9% were myotonic, dystrophy 25.8% DBMD, 9.7% facioscapulohumeral MD, and 9.1% limb‐girdle MD. Most cases were male (63.6%), non‐Hispanic (59.8%), and White (80.2%). About, half of cases were genetically diagnosed in self (39.1%) or family (6.2%). About, half had a family history of MD (48.9%). The hereditary progressive MD code (359.1) was the most common code for identifying eligible cases. The myotonic code (359.21) identified 83.4% of eligible myotonic dystrophy cases (786/943).

Conclusions

MD STARnet is the only multisite, population‐based active surveillance system available for MD in the United States. Continuing our expanded surveillance will contribute important epidemiologic and health outcome information about several MDs.
The Expression Pattern of the Phosphoproteome Is Significantly Changed During the Growth Phases of Recombinant CHO Cell Culture
Authors: Kaushik Prashant , Henry Michael , Clynes Martin , Meleady Paula
Published: August 2018

Post‐translational modification of proteins by reversible phosphorylation plays a pivotal role in regulating key cellular processes including transcription, translation, cell proliferation, differentiation, apoptosis, and signal transduction. Despite the importance of the phosphorylation level of regulation, little work has been carried out on the phosphoproteomic characterization of Chinese hamster ovary (CHO) cells in bioprocess‐relevant conditions. Growth control strategies are often used to prolong culture duration and increase specific productivity; however, the cellular mechanisms and regulatory pathways underlying growth strategies are poorly understood in CHO cells. Phosphorylation changes are dynamic and will respond to changes in culture conditions; this may reflect the status of the cells with respect to growth and viability of the culture. Herein, this study uses a phosphopeptide enrichment strategy in conjunction with LC‐MS/MS to carry out a large‐scale differential phosphoproteomic analysis of IgG producing CHO DP12 cells at various phases of growth in serum‐free suspension batch culture to characterize dynamic changes to the phosphoproteome with changing culture conditions. In total over the various growth phases, 3777 differentially expressed unique phosphopeptides are identified from 1415 differentially expressed unique phosphoproteins. Analysis of the whole cell lysate without phosphopeptide enrichment over the various growth phases revealed the differential expression of 834 unique proteins, with an overlap of 188 proteins between the proteomic and phosphoproteomic analyses. The inclusion of phosphoproteomic data significantly improves proteome coverage but also gives insights into the post‐translational level of regulation during cellular growth of recombinant CHO cells.