bluuebunny/crossref_metadata_2025 huggingface dataset:
Porencephaly in a fetus and HANAC in her father: Variable expression of COL4A1 mutation
Authors: Takenouchi Toshiki , Ohyagi Masaki , Torii Chiharu , Kosaki Rika , Takahashi Takao , Kosaki Kenjiro
Published: November 2014

COL4A1‐associated disorders encompass a wide range of hereditary vasculopathy, including porencephaly and HANAC (adult‐onset hemorrhagic stroke with cerebral aneurysm and retinal arterial tortuosity, renal cysts, and thenar muscle cramp). It remains elusive whether or not porencephaly and HANAC are molecularly distinctive disorders due to different classes of mutations. We report on a girl with porencephaly and an episode of microangiopathic hemolysis in infancy and her father with HANAC, both of whom had a heterozygous missense mutation of COL4A1 (c.3715G>A, p.G1239R). The current observation implies phenotypic diversities of COL4A1 mutations. © 2014 Wiley Periodicals, Inc.
Mosaicism and clinical genetics
Authors: Spinner Nancy B. , Conlin Laura K.
Published: November 2014

With the introduction of increasingly sensitive technologies for mutation detection such as chromosomal microarrays and next‐generation sequencing, the importance of mosaicism for human disease is being more fully appreciated. Mosaicism can occur for any type of mutation, either at the chromosomal or DNA sequence level, and while in many cases mosaicism can modify the clinical effects of a syndrome, there are many alterations that can only occur in mosaic form as the mutation is lethal when present in every cell. Mosaicism can have a wide range of effects, from early pregnancy loss, to organ specific pathology, to modification of clinical syndromes. Recent evidence reveals that generation of mosaic alterations is associated with aging, and our ability to detect mosaic alterations sheds light on normal and pathologic changes across the lifespan. © 2014 Wiley Periodicals, Inc.
A Bis‐Sulfonyl O,C,O Aryl Pincer Ligand and its Tin(II) Complex: Synthesis, Structural Studies, and DFT Calculations
Authors: El Ezzi Mohammad , Lenk Romaric , Madec David , Sotiropoulos Jean‐Marc , Mallet‐Ladeira Sonia , Castel Annie
Published: November 2014

The efficiency of the deprotonated aryl bis‐sulfone [2,6‐{(p‐tolyl)SO2}2C6H3]− as an O,C,O‐coordinating pincer‐type ligand was described. The bis‐sulfone precursor was synthesized using a straightforward palladium‐catalyzed cross‐coupling reaction. As a result of directed ortho metalation (DoM) through sulfonyl groups, a selective lithiation of the aryl group was achieved and the corresponding carbanion was isolated and its structure determined by single‐crystal X‐ray diffraction analysis. A heteroleptic tin(II) complex has been prepared by a nucleophilic substitution reaction. Crystallographic analysis and DFT calculations indicate that the bis‐sulfonyl moiety acts as a new O,C,O‐coordinating pincer‐type ligand with intramolecular SO coordination to a tin(II) center. The cis form with the two nonbonded oxygen atoms of the sulfonyl groups on the same side is preferentially obtained.
Enantioselective Oxidative Gold Catalysis Enabled by a Designed Chiral P,N‐Bidentate Ligand
Authors: Ji Kegong , Zheng Zhitong , Wang Zhixun , Zhang Liming
Published: November 2014

A newly developed P,N‐bidentate ligand enables enantioselective intramolecular cyclopropanation by a reactive α‐oxo gold carbene intermediate generated in situ. The ligand design is based on our previously proposed structure (with a well‐organized triscoordinated gold center) of the carbene intermediate in the presence of a P,N‐bidentate ligand. A C2‐symmetric piperidine ring was incorporated in the ligand as the nitrogen‐containing moiety. A range of racemic transformations of α‐oxo gold carbene intermediates have been developed recently, and this new class of chiral ligands could enable their modification for asymmetric synthesis, as demonstrated in this study.
Schaltung bakterieller Adhäsion auf glycosylierten Oberflächen durch reversible Reorientierung der Kohlenhydratliganden
Authors: Weber Theresa , Chandrasekaran Vijayanand , Stamer Insa , Thygesen Mikkel B. , Terfort Andreas , Lindhorst Thisbe K.
Published: November 2014

In vielen biologischen Systemen wird die Erkennung von Oberflächen durch die Wechselwirkung von Kohlenhydrat‐spezifischen Proteinen (Lektinen) mit den Kohlenhydratepitopen (Liganden) der ungeordneten Glycokonjugatschicht (Glycokalyx) der Zellen gesteuert. Damit es zu einer erfolgreichen Anbindung kommt, müssen sich diese Liganden geeignet im Raum orientieren. Wir stellen zum ersten Mal ein Modellsystem vor, in dem die Orientierung der Liganden auf einer Oberfläche kontrolliert variiert wird, ohne dabei ihre strukturelle Qualität in irgendeiner Weise zu verändern. Der Schlüssel für die Kontrolle der Ligandorientierung liegt in der Konjugation an photoschaltbare Azobenzoleinheiten.
Functional Dynamics of Deuterated β2‐Adrenergic Receptor in Lipid Bilayers Revealed by NMR Spectroscopy
Authors: Kofuku Yutaka , Ueda Takumi , Okude Junya , Shiraishi Yutaro , Kondo Keita , Mizumura Takuya , Suzuki Shiho , Shimada Ichio
Published: November 2014

G‐protein‐coupled receptors (GPCRs) exist in conformational equilibrium between active and inactive states, and the former population determines the efficacy of signaling. However, the conformational equilibrium of GPCRs in lipid bilayers is unknown owing to the low sensitivities of their NMR signals. To increase the signal intensities, a deuteration method was developed for GPCRs expressed in an insect cell/baculovirus expression system. The NMR sensitivities of the methionine methyl resonances from the β2‐adrenergic receptor (β2AR) in lipid bilayers of reconstituted high‐density lipoprotein (rHDL) increased by approximately 5‐fold upon deuteration. NMR analyses revealed that the exchange rates for the conformational equilibrium of β2AR in rHDLs were remarkably different from those measured in detergents. The timescales of GPCR signaling, calculated from the exchange rates, are faster than those of receptor tyrosine kinases and thus enable rapid neurotransmission and sensory perception.
Indicator Displacement Assays Inside Live Cells
Authors: Norouzy Amir , Azizi Zahra , Nau Werner M.
Published: November 2014

The macrocycle p‐sulfonatocalix[4]arene (CX4) and the fluorescent dye lucigenin (LCG) form a stable host–guest complex, in which the dye fluorescence is quenched. Incubation of live V79 and CHO cells with the CX4/LCG chemosensing ensemble resulted in its spontaneous uptake. Subsequent addition of choline, acetylcholine, or protamine, which have a high affinity for CX4 and are capable of entering cells, resulted in a fluorescence switch‐on response. This can be traced to the displacement of LCG from CX4 by the analytes. The results establish the principal functionality of indicator displacement assays with synthetic receptors for the detection of the uptake of bioorganic analytes by live cells.
“Post‐It” Type Connected DNA Created with a Reversible Covalent Cross‐Link
Authors: Tomás‐Gamasa María , Serdjukow Sascha , Su Meng , Müller Markus , Carell Thomas
Published: November 2014

We report the development of a new heterobase that is held together through reversible bonding. The so‐formed cross‐link adds strong stabilization to the DNA duplex. Despite this, the cross‐link opens and closes through reversible imine bonding. Moreover, even enzymatic incorporation of the cross‐link is possible. The new principle can be used to stabilize DNA duplexes and nanostructures that otherwise require high salt concentrations, which may hinder biological applications.
Interception of Cobalt‐Based Carbene Radicals with α‐Aminoalkyl Radicals: A Tandem Reaction for the Construction of β‐Ester‐γ‐amino Ketones
Authors: Zhang Jie , Jiang Jiewen , Xu Dongmei , Luo Qiang , Wang Hongxiang , Chen Jijun , Li Huihuang , Wang Yaxiong , Wan Xiaobing
Published: November 2014

The interception of cobalt‐based carbene radicals with α‐aminoalkyl radicals was combined with the Kornblum–DeLaMare reaction and provides β‐ester‐γ‐amino ketones, which are otherwise difficult to obtain in high chemoselectivity. Mechanistically, this transformation is an interplay of cobalt‐based carbene radicals, organoradicals, and ionic intermediates and involves the construction of two CC bonds and one CO bond in a one‐pot process. The reaction also features a wide substrate scope and is highly efficient and insensitive to moisture and air.
Solvation Dynamics of a Single Water Molecule Probed by Infrared Spectra—Theory Meets Experiment
Authors: Wohlgemuth Matthias , Miyazaki Mitsuhiko , Weiler Martin , Sakai Makoto , Dopfer Otto , Fujii Masaaki , Mitrić Roland
Published: November 2014

The dynamics and energetics of water at interfaces or in biological systems plays a fundamental role in all solvation and biological phenomena in aqueous solution. In particular, the migration of water molecules is the first step that controls the overall process in the time domain. Experimentally, the dynamics of individual water molecules is nearly impossible to follow in solution, because signals from molecules in heterogeneous environments overlap. Although molecular dynamics simulations do not have this restriction, there is a lack of experimental data to validate the calculated dynamics. Here, we demonstrate a new strategy, in which the calculated dynamics are verified by measured time‐resolved infrared spectra. The coexistence of fast and slow migrations of water molecules around a CONH peptide linkage is revealed for a model system representative of a hydrate peptide.
Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)
Authors: Miyatake‐Ondozabal Hideki , Kaufmann Elias , Gademann Karl
Published: November 2014

Fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is a novel macrocyclic antibiotic that is used in hospitals for the treatment of Clostridium difficile infections. This natural product has also been shown to have excellent bactericidal activity against multidrug‐resistant Mycobacterium tuberculosis. In spite of its attractive biological activity, no total synthesis has been reported to date. The enantioselective synthesis of the central 18‐membered macrolactone is reported herein. The key reactions include ring‐closing metathesis between a terminal olefin and a dienoate moiety for macrocyclization, a vinylogous Mukaiyama aldol reaction, and a Stille coupling reaction of sterically demanding substrates. The retrosynthesis involves three medium‐sized fragments, thus leading to a flexible yet convergent synthetic route.
Nickel‐Catalyzed Dehydrogenative Cross‐Coupling: Direct Transformation of Aldehydes into Esters and Amides
Authors: Whittaker Aaron M. , Dong Vy M.
Published: November 2014

By exploring a new mode of nickel‐catalyzed cross‐coupling, a method to directly transform both aromatic and aliphatic aldehydes into either esters or amides has been developed. The success of this oxidative coupling depends on the appropriate choice of catalyst and organic oxidant, including the use of either α,α,α‐trifluoroacetophenone or excess aldehyde. Mechanistic data that supports a catalytic cycle involving oxidative addition into the aldehyde CH bond is also presented.
Hybrid Ruthenium ROMP Catalysts Based on an Engineered Variant of β‐Barrel Protein FhuA ΔCVFtev: Effect of Spacer Length
Authors: Sauer Daniel F. , Bocola Marco , Broglia Claudio , Arlt Marcus , Zhu Lei‐Lei , Brocker Melanie , Schwaneberg Ulrich , Okuda Jun
Published: November 2014

A biohybrid ring‐opening olefin metathesis polymerization catalyst based on the reengineered β‐barrel protein FhuA ΔCVFtev was chemically modified with respect to the covalently anchored Grubbs–Hoveyda type catalyst. Shortening of the spacer (1,3‐propanediyl to methylene) between the N‐heterocyclic carbene ligand and the cysteine site 545 increased the ROMP activity toward a water‐soluble 7‐oxanorbornene derivative. The cis/trans ratio of the double bond in the polymer was influenced by the hybrid catalyst.
Short Protecting Group‐free Syntheses of Camptothecin and 10‐Hydroxycamptothecin Using Cascade Methodologies
Authors: Xu Peng , Chen Dong‐Sheng , Xi Jie , Yao Zhu‐Jun
Published: November 2014

A convergent protecting group‐free total synthesis route of camptothecin and 10‐hydroxycamptothecin has been developed in this work. Cascade oxidation of 3‐(hydroxymethyl)furan‐2(5 H)‐one and in situ intermolecular oxa Diels–Alder reaction with vinyl ether was developed and applied to construct the E‐ring, and TMSCl‐promoted cascade closure of the D‐ring delivered the whole skeleton of the alkaloids in the total synthesis. The new short syntheses were advantageous with regard to step economy, low cost, easily available starting materials and reagents, and convenient operations.
Development and physiological characterization of cellobiose‐consuming Yarrowia lipolytica
Authors: Lane Stephan , Zhang Shuyan , Wei Na , Rao Christopher , Jin Yong‐Su
Published: November 2014

Yarrowia lipolytica is a promising production host for a wide range of molecules, but limited sugar consumption abilities prevent utilization of an abundant source of renewable feedstocks. In this study we created a Y. lipolytica strain capable of utilizing cellobiose as a sole carbon source by using endogenous promoters to express the cellodextrin transporter cdt‐1 and intracellular β‐glucosidase gh1‐1 from Neurospora crassa. The engineered strain was also capable of simultaneous co‐consumption of glucose and cellobiose. Although cellobiose was consumed slower than glucose when engineered strains were cultured with excess nitrogen, culturing with limited nitrogen led to cellobiose consumption rates comparable to those of glucose. Under limited nitrogen conditions, the engineered strain produced citric acid as a major product and we observed greater citric acid yields from cellobiose (0.37 g/g) than glucose (0.28 g/g). Culturing with a sole carbon source of either glucose or cellobiose induced additional differences on cell physiology and metabolism and a link is suggested to evasion of glucose‐sensing mechanisms through intracellular creation and consumption of glucose. We ultimately applied this cellobiose‐utilization system to produce citric acid from bioconversion of crystalline cellulose through simultaneous saccharification and fermentation (SSF). Biotechnol. Bioeng. 2015;112: 1012–1022. © 2014 Wiley Periodicals, Inc.
A simple and low‐cost platform technology for producing pexiganan antimicrobial peptide in E. coli
Authors: Zhao Chun‐Xia , Dwyer Mirjana Dimitrijev , Yu Alice Lei , Wu Yang , Fang Sheng , Middelberg Anton P.J.
Published: November 2014

Antimicrobial peptides, as a new class of antibiotics, have generated tremendous interest as potential alternatives to classical antibiotics. However, the large‐scale production of antimicrobial peptides remains a significant challenge. This paper reports a simple and low‐cost chromatography‐free platform technology for producing antimicrobial peptides in Escherichia coli (E. coli). A fusion protein comprising a variant of the helical biosurfactant protein DAMP4 and the known antimicrobial peptide pexiganan is designed by joining the two polypeptides, at the DNA level, via an acid‐sensitive cleavage site. The resulting DAMP4var‐pexiganan fusion protein expresses at high level and solubility in recombinant E. coli, and a simple heat‐purification method was applied to disrupt cells and deliver high‐purity DAMP4var‐pexiganan protein. Simple acid cleavage successfully separated the DAMP4 variant protein and the antimicrobial peptide. Antimicrobial activity tests confirmed that the bio‐produced antimicrobial peptide has the same antimicrobial activity as the equivalent product made by conventional chemical peptide synthesis. This simple and low‐cost platform technology can be easily adapted to produce other valuable peptide products, and opens a new manufacturing approach for producing antimicrobial peptides at large scale using the tools and approaches of biochemical engineering. Biotechnol. Bioeng. 2015;112: 957–964. © 2014 Wiley Periodicals, Inc.
Expectations of Emotions during Testimony: The Role of Communicator and Perceiver Characteristics
Authors: Bederian‐Gardner Daniel , Goldfarb Deborah
Published: November 2014

This study investigated the influence of communicator (child victim) and perceiver (adult participant) characteristics on expectations about witnesses’ emotional displays during testimony. In total, 191 adults were asked whether or not they expected child victims who were testifying about sexual abuse to display sadness, fear, anger, disgust, happiness, or a neutral demeanor, and how intensely the adults expected each emotion to be displayed. In describing the victims, child age (5 vs. 13 years old) and child gender (female vs. male) were factorially combined as within‐subject factors. Results included that victim gender predicted expectations of fear, and victim age predicted expectations of anger and disgust. There was a significant interaction of victim age and victim gender for expectations of sadness. Of participants who expected multiple emotions, a combination of negative and neutral emotions was expected more from 13‐year‐old female victims than from 5‐year‐old female victims. Child victim empathy predicted ratings of how intensely sad and fearful the child victim would look. Implications of these findings for psychological research and the legal system are discussed. Copyright © 2014 John Wiley & Sons, Ltd.
Explaining Gender Differences in Jurors' Reactions to Child Sexual Assault Cases
Authors: Bottoms Bette L. , Peter‐Hagene Liana C. , Stevenson Margaret C. , Wiley Tisha R. A. , Mitchell Tracey Schneider , Goodman Gail S.
Published: November 2014

In three experiments, we investigated the influence of juror, victim, and case factors on mock jurors' decisions in several types of child sexual assault cases (incest, day care, stranger abduction, and teacher‐perpetrated abuse). We also validated and tested the ability of several scales measuring empathy for child victims, children's believability, and opposition to adult/child sex, to mediate the effect of jurors' gender on case judgments. Supporting a theoretical model derived from research on the perceived credibility of adult rape victims, women compared to men were more empathic toward child victims, more opposed to adult/child sex, more pro‐women, and more inclined to believe children generally. In turn, women (versus men) made more pro‐victim judgments in hypothetical abuse cases; that is, attitudes and empathy generally mediated this juror gender effect that is pervasive in this literature. The experiments also revealed that strength of case evidence is a powerful factor in determining judgments, and that teen victims (14 years old) are blamed more for sexual abuse than are younger children (5 years old), but that perceptions of 5 and 10 year olds are largely similar. Our last experiment illustrated that our findings of mediation generalize to a community member sample. Copyright © 2014 John Wiley & Sons, Ltd.
siRNA blocking the RAS signalling pathway and inhibits the growth of oesophageal squamous cell carcinoma in nude mice
Authors: Wang Xinjie , Zheng Yuling , Fan Qingxia , Zhang Xudong , Shi Yonggang
Published: November 2014

The aim of this study was to study RAS‐siRNA blocking RAS pathway and suppressing cell growth in human oesophageal squamous cell carcinoma in nude mice. The methods in this study was to construct RAS‐siRNA expression vector, establish 40 oesophageal squamous cell carcinoma xenograft animal models and divided them into five groups: control group, siRNA control group, RAS‐siRNA group, paclitaxel group and RAS‐siRNA and paclitaxel group. We observed tumour growth in nude mice, studied histology by HE staining, tumour growth inhibition by TUNEL assay and detected the RAS, MAPK and cyclin D1 protein expression by immunohistochemistry and western blot. We have obtained the following results: (i) successfully established animal models; (ii) nude mice in each group after treatment inhibited tumour volume was significantly reduced compared with the control group (p < 0.05); (iii) compared with the control group, the number of apoptotic cells were significantly increased in the siRNA control group and the RAS‐siRNA group, and the number of apoptosis cells in the paclitaxel and RAS‐siRNA group is significantly most than the paclitaxel group and RAS‐siRNA group (p < 0.05); and (iv) after treatment, RAS, MAPK and cyclin D1 expression in five groups was decreasing gradually. After adding paclitaxel, the protein expression in the paclitaxel and RAS‐siRNA group was significantly lower than that of paclitaxel group, negative control and paclitaxel group (p < 0.05). We therefore conclude that RAS‐siRNA can block the RAS signal transduction pathway, reduce the activity of tumour cells, arrest tumour cell cycle, promote apoptosis, inhibit cell proliferation and increase tumour cell sensitivity to chemotherapeutic drugs. Copyright © 2014 John Wiley & Sons, Ltd.
Diabetic encephalopathy‐related depression: experimental evidence that insulin and clonazepam restore antioxidant status in rat brain
Authors: Wayhs Carlos Alberto Yasin , Mescka Caroline Paula , Guerreiro Gilian , Moraes Tarsila Barros , Jacques Carlos Eduardo Diaz , Rosa Andrea Pereira , Ferri Marcelo Kneib , Nin Maurício Schüler , Dutra‐Filho Carlos Severo , Barros Helena Maria Tannhauser , Vargas Carmen Regla
Published: November 2014

There is increasing evidence suggesting that oxidative stress plays an important role in the development of many chronic and degenerative conditions such as diabetic encephalopathy and depression. Considering that diabetic rats and mice present higher depressive‐like behaviour when submitted to the forced swimming test and that treatment with insulin and/or clonazepam is able to reverse the behavioural changes of the diabetic rats, the present work investigated the antioxidant status, specifically total antioxidant reactivity and antioxidant potential of insulin and clonazepam, as well as the effect of this drugs upon protein oxidative damage and reactive species formation in cortex, hippocampus and striatum from diabetic rats submitted to forced swimming test. It was verified that longer immobility time in diabetic rats and insulin plus clonazepam treatment reversed this depressive‐like behaviour. Moreover, data obtained in this study allowed to demonstrate through different parameters such as protein carbonyl content, 2′7′‐dichlorofluorescein oxidation, catalase, superoxide dismutase, glutathione peroxidase assay, total radical‐trapping antioxidant potential and total antioxidant reactivity that there is oxidative stress in cortex, hippocampus and striatum from diabetic rats under depressive‐like behaviour and highlight the insulin and/or clonazepam effect in these different brain areas, restoring antioxidant status and protein damage. Copyright © 2014 John Wiley & Sons, Ltd.
Propofol inhibits proliferation and induces neuroapoptosis of hippocampal neurons in vitro via downregulation of NF‐κB p65 and Bcl‐2 and upregulation of caspase‐3
Authors: Zhong Yuling , Liang Yubing , Chen Jing , Li Li , Qin Yi , Guan Enjian , He Dan , Wei Yi , Xie Yubo , Xiao Qiang
Published: November 2014

Propofol is widely used in paediatric anaesthesia and intensive care unit because of its essentially short‐acting anaesthetic effect. Recent data have shown that propofol induced neurotoxicity in developing brain. However, the mechanisms are not extremely clear. To gain a better insight into the toxic effects of propofol on hippocampal neurons, we treated cells at the days in vitro 7 (DIV 7), which were prepared from Sprague–Dawley embryos at the 18th day of gestation, with propofol (0.1–1000 μM) for 3 h. A significant decrease in neuronal proliferation and a remarkable increase in neuroapoptosis were observed in DIV 7 hippocampal neurons as measured by 3‐(4,5‐dimethylthiazole‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and apoptosis assay respectively. Moreover, propofol treatment decreased the nuclear factor kappaB (NF‐κB) p65 expression, which was accompanied by a reduction in B‐cell lymphoma 2 (Bcl‐2) mRNA and protein levels, increased caspase‐3 mRNA and activation of caspase‐3 protein. These results indicated that downregulation of NF‐κB p65 and Bcl‐2 were involved in the potential mechanisms of propofol‐induced neurotoxicity. This likely led to the caspase‐3 activation, triggered apoptosis and inhibited the neuronal growth and proliferation that we have observed in our in vitro systems. Copyright © 2014 John Wiley & Sons, Ltd.
Hes1 is upregulated by ischemic postconditioning and contributes to cardioprotection
Authors: Zhou Xue‐liang , Zhao Yong , Fang Yi‐hu , Xu Qi‐rong , Liu Ji‐chun
Published: November 2014

The expression of Hes1 is increased following myocardial infarct and other ischemic cardiomyopathies, but the role of Hes1 in cardioprotection provided by ischemic postconditioning (IPost) remains unclear. In this study, we used gain and loss of function approaches to investigate the role of Hes1 in cardioprotection during IPost. Primary cardiac myocytes exposed to ischemia reperfusion injury (IRI) and IPost were used as the experimental model. The results showed that Hes1 expression was increased during myocardial IPost, and Hes1 promoted the viability while inhibited the apoptosis of cardiomyocytes. Moreover, Hes1 inhibited the opening of mitochondrial permeability transition pore (mPTP) and the generation of reactive oxygen species in primary cardiac myocytes exposed to IRI. Mechanistically, we found that Hes1‐mediated cardioprotection was related to the downregulation of phosphatase and tensin homolog and the activation of phosphatidylinositol 3‐kinase/Akt and signal transducer and activator of transcription 3 signalling. These data demonstrate that Hes1 is upregulated and mediates cardioprotection provided by IPost and suggest that Hes1 is a potential new target for the treatment of ischemic cardiomyopathy. Copyright © 2014 John Wiley & Sons, Ltd.
Particle Size Control and Crystal Habit Modification of Phenacetin Using Ultrasonic Crystallization
Authors: Su Chie‐Shaan , Liao Chieh‐Yun , Jheng Wun‐De
Published: November 2014

Power ultrasound is applied for cooling crystallization to control and modify the particle size and crystal habit of an active pharmaceutical ingredient, phenacetin. Operating parameters including sonication intensity and duration, solution concentration, and cooling rate are studied and compared. With respect to mean particle size, the effect of sonication intensity is most significant. In addition, the crystal habit of recrystallized phenacetin is modified substantially and shows an elliptic shape. Recrystallized phenacetin also provides an enhanced dissolution rate compared with the original sample. These results prove that ultrasonic crystallization is an efficient tool for controlling the solid‐state properties of an active pharmaceutical ingredient.
Numerical Simulation of the Solute‐Induced Marangoni Effect with the Semi‐Lagrangian Advection Scheme
Authors: Chen Jie , Wang Zhihui , Yang Chao , Mao Zai‐Sha
Published: November 2014

The level set method is combined with the concentration transformation method to solve the interphase mass transfer process. However, the artificial diffusion generated in the mass transfer convection term across the interface is inevitable, especially when large shape deformation is encountered at high Reynolds numbers. A semi‐Lagrangian advection scheme is introduced to overcome this disadvantage. The methyl isobutyl ketone (MIBK)‐acetic acid‐water system is adopted to study the unsteady mass transport process accompanied with the Marangoni effect of a single deformable drop ascending in the infinite continuous phase. The predicted overall mass transfer coefficients agree with experimental data very well. The configuration of Marangoni convection is revealed and its effect on the interphase mass transfer process is investigated.
Influence of NaCl on Granulometric Characteristics and Polymorphism in Batch‐Cooling Crystallization of Glycine
Authors: Hrkovac Martina , Kardum Jasna Prlić , Ukrainczyk Neven
Published: November 2014

The effect of NaCl added in different quantities on thermodynamic properties, granulometric characteristics, and structure of glycine in a crystallization process was investigated. Solubilities of α‐ and γ‐polymorphs in the presence of varying amounts of NaCl were analyzed. In order to examine the impact of the additive on granulometric properties of glycine, crystal morphology was examined by observing crystals under a scanning electron microscope. Crystal size distribution was determined by sieve analysis. By X‐ray diffraction analysis, the critical concentration of NaCl at which the structure of glycine changed, could be defined. The purity of obtained polymorphs was confirmed by Fourier transform infrared spectroscopy.
Porous Coordination Polymers of Diverse Topologies Based on a Twisted Tetrapyridylbiaryl: Application as Nucleophilic Catalysts for Acetylation of Phenols
Authors: Seth Saona , Venugopalan Paloth , Moorthy Jarugu Narasimha
Published: November 2014

Porous coordination polymers (CPs) with partially uncoordinated pyridyl rings based on rationally designed polypyridyl linkers are appealing from the point of view of their application as nucleophilic catalysts. A D2d‐symmetric tetradentate organic linker L, that is, 2,2′,6,6′‐tetramethoxy‐3,3′,5,5′‐tetrakis(4‐pyridyl)biphenyl, was designed and synthesized for metal‐assisted self‐assembly aimed at porous CPs. Depending on the nature of the metal ion and the counter anion, the ligand L is found to function as a 3‐ or 4‐connecting building block leading to porous CPs of diverse topologies. The reaction of L with Zn(NO3)2 and Cd(NO3)2 yields porous 2 D CPs of “fes” topology, in which the tetrapyridyl linker L serves as a 3‐connecting unit with its free pyridyl rings well exposed into the pores. The functional utility of these porous CPs containing uncoordinated pyridyl rings is demonstrated by employing them as efficient heterogeneous nucleophilic catalysts for acetylation of a number of phenols with varying electronic properties and reactivities.
Electron Transfer‐Initiated Epoxidation and Isomerization Chain Reactions of β‐Caryophyllene
Authors: Steenackers Bart , Campagnol Nicolò , Fransaer Jan , Hermans Ive , De Vos Dirk
Published: November 2014

The abundant sesquiterpene β‐caryophyllene can be epoxidized by molecular oxygen in the absence of any catalyst. In polar aprotic solvents, the reaction proceeds smoothly with epoxide selectivities exceeding 70 %. A mechanistic study has been performed and the possible involvement of free radical, spin inversion, and electron transfer mechanisms is evaluated using experimental and computational methods. The experimental data—including a detailed reaction product analysis, studies on reaction parameters, solvent effects, additives and an electrochemical investigation—all support that the spontaneous epoxidation of β‐caryophyllene constitutes a rare case of unsensitized electron transfer from an olefin to triplet oxygen under mild conditions (80 °C, 1 bar O2). As initiation of the oxygenation reaction, the formation of a caryophyllene‐derived radical cation via electron transfer is proposed. This radical cation reacts with triplet oxygen to a dioxetane via a chain mechanism with chain lengths exceeding 100 under optimized conditions. The dioxetane then acts as an in situ‐formed epoxidizing agent. Under nitrogen atmosphere, the presence of a one‐electron acceptor leads to the selective isomerization of β‐caryophyllene to isocaryophyllene. Observations indicate that this isomerization reaction is a novel and elegant synthetic pathway to isocaryophyllene.
Can CH⋅⋅⋅π Interactions Be Used To Design Single‐Chain Magnets?
Authors: Singh Mukesh Kumar , Rajaraman Gopalan
Published: November 2014

This theoretical study suggests that CH⋅⋅⋅π stacking interactions between monomeric units can be used to design novel single‐chain magnets (SCMs), as the sign of coupling is predictable and such chains inherently yield negative axial anisotropy, a condition often difficult to achieve in conventional SCMs.
Ruthenium(II)‐Catalyzed CH Acyloxylation of Phenols with Removable Auxiliary
Authors: Raghuvanshi Keshav , Rauch Karsten , Ackermann Lutz
Published: November 2014

Intermolecular CH acyloxylations of phenols with removable directing groups were accomplished with a versatile ruthenium catalyst. Specifically, a cationic ruthenium(II) complex, formed in situ, enabled the chemoselective CH oxygenations of a broad range of substrates. The catalyst proved tolerant of synthetically valuable functional groups, and the substrate scope included both (hetero)aromatic and, the more challenging, aliphatic carboxylic acids. The proposed reaction mechanism involves a reversible CH ruthenation and an oxidatively induced CO‐bond‐forming reductive elimination.
Oxoanionic Noble Metal Compounds from Fuming Nitric Acid: The Palladium Examples Pd(NO3)2 and Pd(CH3SO3)2
Authors: Bruns Jörn , Klüner Thorsten , Wickleder Mathias S.
Published: November 2014

The oxidation of elemental palladium at 100 °C in a mixture of fuming nitric acid and a pyridine‐SO3 complex leads to the anhydrous nitrate Pd(NO3)2 (monoclinic, P21/n, Z=2, a=469.12(3) pm, b=593.89(3) pm, c=805.72(4) pm, β=105.989(3)°, V=215.79(2) Å3). The Pd2+ ions are in square‐planar coordination with four monodentate nitrate groups which are connected to further palladium atoms, leading to a layer structure. The reaction of elemental palladium with a mixture of fuming nitric acid and methanesulfonic acid at 120 °C leads to single crystals of Pd(CH3SO3)2 (monoclinic, P21/n, Z=2, a=480.44(1) pm, b=1085.53(3) pm, c=739.78(2) pm, β=102.785(1)°, V=376.254(17) Å3). Also in this structure the Pd2+ ions are in square‐planar coordination with four monodentate anions; however, the connection to adjacent palladium atoms leads to a chain‐type structure. The thermal decomposition of the compounds has been investigated by means of DSC/TG measurements. Furthermore, IR and Raman spectra have been recorded, and an assignment of the observed vibrational frequencies has been carried out based on theoretical investigations.
New Polyoxometalates Containing Hybrid Polymers and Their Potential for Nano‐Patterning
Authors: Kalyani Vishwanath , Satyanarayana V. S. V. , Singh Vikram , Pradeep Chullikkattil P. , Ghosh Subrata , Sharma Satinder K. , Gonsalves Kenneth E.
Published: November 2014

Two new polyoxometalate (POM)‐based hybrid monomers (Bu4N)5(H)[P2V3W15O59{(OCH2)3CNHCO(CH3)CCH2}] (2) and (S(CH3)2C6H4OCOC(CH3)=CH2)6[PVMo10O40] (5) were developed by grafting polymerizable organic units covalently or electrostatically onto Wells–Dawson and Keggin‐type clusters and were characterized by analytical and spectroscopic techniques including ESI‐MS and/or single‐crystal X‐ray diffraction analyses. Radical initiated polymerization of 2 and 5 with organic monomers (methacryloyloxy)phenyldimethylsulfonium triflate (MAPDST) and/or methylmethacrylate (MMA) yielded a new series of POM/polymer hybrids that were characterized by 1H, 31P NMR and IR spectroscopic techniques, gel‐permeation chromatography as well as thermal analyses. Preliminary tests were conducted on these POM/polymer hybrids to evaluate their properties as photoresists using electron beam (E‐beam)/extreme ultraviolet (EUV) lithographic techniques. It was observed that the POM/polymer hybrid of 2 with MAPDST exhibited improved sensitivity under EUV lithographic conditions in comparison to the MAPDST homopolymer resist possibly due to the efficient photon harvesting by the POM clusters from the EUV source.
Electrochemical Properties of Yolk–Shell‐Structured Zn–Fe–S Multicomponent Sulfide Materials with a 1:2 Zn/Fe Molar Ratio
Authors: Won Jong Min , Lee Jong‐Heun , Kang Yun Chan
Published: November 2014

Yolk–shell‐structured Zn–Fe–S multicomponent sulfide materials with a 1:2 Zn/Fe molar ratio were prepared applying a sulfidation process to ZnFe2O4 yolk–shell powders. The Zn–Fe–S powders had mixed sphalerite (Zn,Fe)S and hexagonal FeS crystal structures. The discharge capacities of the Zn–Fe–S powders sulfidated at 350 °C at a constant current density of 500 mA g−1 for the first, second, and fiftieth cycles were 1098, 912, and 913 mA h g−1, respectively. The powders exhibited a high discharge capacity of 602 mA h g−1 even at the high current density of 10 A g−1. The synergistic effect of yolk–shell structure and multicomponent composition improved the electrochemical properties of Zn–Fe–S powders.
Copper‐Catalyzed Difunctionalization of Activated Alkynes by Radical Oxidation–Tandem Cyclization/Dearomatization to Synthesize 3‐Trifluoromethyl Spiro[4.5]trienones
Authors: Hua Hui‐Liang , He Yu‐Tao , Qiu Yi‐Feng , Li Ying‐Xiu , Song Bo , Gao Pin , Song Xian‐Rong , Guo Dong‐Hui , Liu Xue‐Yuan , Liang Yong‐Min
Published: November 2014

A copper‐catalyzed difunctionalizing trifluoromethylation of activated alkynes with the cheap reagent sodium trifluoromethanesulfinate (NaSO2CF3 or Langlois’ reagent) has been developed incorporating a tandem cyclization/dearomatization process. This strategy affords a straightforward route to synthesis of 3‐(trifluoromethyl)‐spiro[4.5]trienones, and presents an example of difunctionalization of alkynes for simultaneous formation of two carbon–carbon single bonds and one carbon–oxygen double bond.
Highly Sensitive INHIBIT and XOR Logic Gates Based on ICT and ACQ Emission Switching of a Porphyrin Derivative
Authors: Xu Xiao‐Ling , Lin Fu‐Wen , Xu Wei , Wu Jian , Xu Zhi‐Kang
Published: November 2014

Fluorescence‐switch‐based logic devices are very sensitive compared with most of the reported devices based on UV/Vis absorption systems. Herein, we demonstrate that a simple molecule, 5,10,15,20‐tetra‐(4‐aminophenyl)porphyrin (TAPP), shows protonation‐induced multiple emission switches through intramolecular charge transfer and/or aggregation‐caused quenching. Highly sensitive INHIBIT and XOR logic gates can be achieved by combining the intermolecular assembly with the intramolecular photoswitching of diprotonated TAPP (TAPPH22+). In addition, molecular simulations have been performed by DFT for a better understanding of the emission‐switching processes.
Asymmetric anti‐Selective Michael Reaction of Imidazole‐Modified Ketones with trans‐β‐Nitroalkenes
Authors: Yang Dongxu , Wang Linqing , Li Dan , Han Fengxia , Zhao Depeng , Wang Rui
Published: November 2014

The successful application of imidazole‐modified ketones in asymmetric anti‐selective Michael reactions with trans‐β‐nitroalkenes is presented by employing a newly developed 3‐bromothiophene‐modified chiral diamine ligand. The corresponding conjugate adduct was submitted to further transformations with Grignard reagents to solve the problem of α‐site selectivity of simple linear ketones. Additionally, the syn‐selective product was obtained by treating the anti‐selective adduct with a simple base. In this way, the site‐specific products for both diastereomers in the asymmetric conjugate addition of simple ketones to nitroalkenes can be obtained.
Formal [4+2] Reaction between 1,3‐Diynes and Pyrroles: Gold(I)‐Catalyzed Indole Synthesis by Double Hydroarylation
Authors: Matsuda Yuka , Naoe Saori , Oishi Shinya , Fujii Nobutaka , Ohno Hiroaki
Published: November 2014

Indole synthesis by a gold(I)‐catalyzed intermolecular formal [4+2] reaction between 1,3‐diynes and pyrroles has been developed. This reaction involves the hydroarylation of 1,3‐diynes with pyrroles followed by an intramolecular hydroarylation to give the 4,7‐disubstituted indoles. This reaction can also be applied to the synthesis of carbazoles when indoles are used as the nucleophiles instead of pyrroles.
Intramolecular CN Bond Activation and Ring‐Expansion Reactions of N‐Heterocyclic Carbenes
Authors: Hemberger Patrick , Bodi Andras , Berthel Johannes H. J. , Radius Udo
Published: November 2014

Intramolecular ring‐expansion reactions (RER) of the N‐heterocyclic carbene 1,3‐dimethylimidazolin‐2‐ylidene were observed upon vacuum ultraviolet (VUV) photoexcitation. Similarly to RERs reported in the solvent phase, for the reaction of NHCs with main‐group‐element hydrides, hydrogen transfer to the NHC carbon atom is the crucial initial step. In an ionization‐mediated protonation, 1,3‐dimethylimidazolin‐2‐ylidene forms an imidazolium ion, which is the rate‐limiting step on the pathway to two six‐membered ring products, namely, methylpyrimidinium and ‐pyrazinium ions. To unravel the reaction path, we have used imaging photoelectron photoion coincidence spectroscopy with VUV synchrotron radiation, as well as high‐level composite method calculations. Similarities and differences between the mechanism in the gas phase and in the condensed phase are discussed.
Should small papillary thyroid cancer be observed? A population‐based study
Authors: Nilubol Naris , Kebebew Electron
Published: November 2014

BACKGROUND

Some centers have advocated selecting patients with small papillary thyroid cancer (PTC) to undergo active surveillance without surgical treatment. The objectives of the current study were to analyze thyroid cancer (TC)‐related mortality in a population‐based cohort and to determine the impact of small PTCs (defined as tumors ≤2 cm in greatest dimension) on TC‐related mortality.

METHODS

Data on patients with TC of follicular cell origin from the National Cancer Institute's Surveillance, Epidemiology, and End Results 17 Registries database (1988‐2007) were used to analyze the characteristics of PTCs ≤2 cm in patients who died from TC‐related causes. The effects of clinical features on disease‐specific survival were analyzed.

RESULTS

Over the 20‐year study period, the rate of TC‐related mortality was 2.8% (n = 1753 of 61,523 patients). Of the patients who died from TC‐related causes, 38% had PTC, 10% had follicular TC, and 31.3% had anaplastic TC. PTCs ≤2 cm accounted for 12.3% of TC‐related mortalities. Compared with patients who did not experience TC‐related mortality from PTCs ≤2 cm, there were significantly higher rates of men (30% vs 17%;P < .01), patients aged ≥45 years (92% vs 52%;P < .01), tumors measuring >1 cm (59% vs 46%;P < .01), extrathyroid extension (41% vs 11%;P < .01), lymph node metastases (77% vs 28%;P < .01), and distant metastases (31% vs 1%;P < .01) among the patients who died from PTCs ≤2 cm. Independent risk factors for death from PTCs ≤2 cm included age ≥45 years, lymph node and distant metastases, extrathyroid extension, and undergoing less than thyroid lobectomy.

CONCLUSIONS

Because 12.3% of patients who experienced TC‐related deaths had PTCs ≤2 cm despite undergoing thyroidectomy, the current results indicate that nonoperative management for patients who have PTCs ≤2 cm should be used with caution. Patients aged ≥45 years with PTCs ≤2 cm should undergo thyroidectomy.Cancer 2015;121:1017–1024.©2014 American Cancer Society.
Sodium channel β1 subunit localizes to axon initial segments of excitatory and inhibitory neurons and shows regional heterogeneity in mouse brain
Authors: Wimmer Verena C. , Harty Rosemary C. , Richards Kay L. , Phillips A. Marie , Miyazaki Haruko , Nukina Nobuyuki , Petrou Steven
Published: November 2014

The β1 subunit of voltage‐gated sodium channels, Navβ1, plays multiple roles in neurons spanning electrophysiological modulation of sodium channel α subunits to cell adhesion and neurite outgrowth. This study used immunohistochemistry to investigate Navβ1 subneuronal and regional expression. Navβ1 was enriched at axon initial segments (AIS) and nodes of Ranvier. Navβ1 expression at the AIS was detected throughout the brain, predominantly in the hippocampus, cortex, and cerebellum. Despite expression of Navβ1 in both excitatory and inhibitory AIS, it displayed a marked and fine‐grained heterogeneity of expression. Such heterogeneity could have important implications for the tuning of single neuronal and regional excitability, especially in view of the fact that Navβ1 coexpressed with Nav1.1, Nav1.2, and Nav1.6 subunits. The disruption of Navβ1 AIS expression by a human epilepsy‐causing C121W genetic mutation in Navβ1 was also investigated using a mouse model. AIS expression of Navβ1 was reduced by approximately 50% in mice heterozygous for the C121W mutation and was abolished in homozygotes, suggesting that loss of Navα subunit modulation by Navβ1 contributes to the mechanism of epileptogenesis in these animals as well as in patients. J. Comp. Neurol. 523:814–830, 2015. © 2015 Wiley Periodicals, Inc.
Parallelizing the execution of native data mining algorithms for computational biology
Authors: Coro Gianpaolo , Candela Leonardo , Pagano Pasquale , Italiano Angela , Liccardo Loredana
Published: November 2014

Data mining is being increasingly used in biology. Biologists are adopting prototyping languages, like R and Matlab, to facilitate the application of data mining algorithms to their data. As a result, their scripts are becoming increasingly complex and also require frequent updates. Application to large datasets becomes impractical and the time‐to‐paper increases. Furthermore, even if there are various systems that can be used to efficiently process large datasets, for example, using Cloud and High Performance Computing, they usually require procedures to be translated into specific languages or to be adapted to a certain computing platform. Such modifications can speed up the processing, but translation is not automatic, especially in complex cases, and can require a large amount of programming effort and accurate validation. In this paper, we propose an approach to parallelize data mining procedures in the form of compiled software or R scripts developed by biology communities of practice. Our approach requires minimal alteration of the original code. In many cases, there is no need for code modification. Furthermore, it allows for fast updating when a new version is ready. We clarify the constraints and the benefits of our method and report a practical use case to demonstrate such benefits compared with a standard execution. Our approach relies on a distributed network of web services and ultimately exposes the algorithms as‐a‐Service, to be invoked by remote thin clients. Copyright © 2014 John Wiley & Sons, Ltd.
Divide‐and‐conquer approach for solving singular value decomposition based on MapReduce
Authors: Zhao Shuoyi , Li Ruixuan , Tian Wenlong , Xiao Weijun , Dong Xinhua , Liao Dongjie , Khan Samee U. , Li Keqin
Published: November 2014

Singular value decomposition (SVD) shows strong vitality in the area of information analysis and has significant application value in most of the scientific big data fields. However, with the rapid development of Internet, the information online reveals fast growing trend. For a large‐scale matrix, applying SVD computation directly is both time consuming and memory demanding. There are many works available to speed up the computation of SVD based on the message passing interface model. However, to deal with large‐scale data processing, a MapReduce model has many advantages over a message passing interface model, such as fault tolerance, load balancing and simplicity. For a MapReduce environment, existing approaches only focus on low rank SVD approximation and tall‐and‐skinny matrix SVD computation, and there are no implementations of full rank SVD computation. In this paper, we propose a MapReduce‐based implementation for solving divide‐and‐conquer SVD algorithm. To achieve high performance, we design a two‐stage task scheduling strategy based on the mathematical characteristics of divide‐and‐conquer SVD algorithm. To further strengthen the performance, we propose a row‐index‐based divide algorithm, a pipelined task scheduling method, and revised block matrix multiplication in MapReduce framework. Experimental result shows the efficiency of our algorithm. Our implementation can accommodate full rank SVD computation of large‐scale matrix very efficiently. Copyright © 2014 John Wiley & Sons, Ltd.