bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrocarbierung von CC‐Bindungen: Quantifizierung der nucleophilen Reaktivität von Inamiden
Authors: Laub Hans A. , Evano Gwilherm , Mayr Herbert
Published: April 2014

Reaktionen von Donor‐substituierten Diarylcarbeniumionen Ar2CH+ mit Inamiden liefern 1‐Amid‐substituierte Allylkationen (α,β‐ungesättigte Iminiumionen). Kinetische Studien zeigen, dass diese Additionsprodukte einer C‐H‐Bindung an eine CC‐Dreifachbindung stufenweise gebildet werden, wobei zunächst Keteniminiumionen entstehen, die anschließend eine 1,3‐Hydridwanderung eingehen. Die linearen Korrelationen der Geschwindigkeitskonstanten zweiter Ordnung (lg k2, 20 °C) mit den Elektrophilie‐Parametern E der Diarylcarbeniumionen ermöglichen es, Inamide in unsere umfassende Nucleophilieskala einzugliedern und dadurch potentielle elektrophile Reaktionspartner vorherzusagen.
Chiral Anion Phase Transfer of Aryldiazonium Cations: An Enantioselective Synthesis of C3‐Diazenated Pyrroloindolines
Authors: Nelson Hosea M. , Reisberg Solomon H. , Shunatona Hunter P. , Patel Jigar S. , Toste F. Dean
Published: April 2014

Herein is reported the first asymmetric utilization of aryldiazonium cations as a source of electrophilic nitrogen. This is achieved through a chiral anion phase‐transfer pyrroloindolinization reaction that forms C3‐diazenated pyrroloindolines from simple tryptamines and aryldiazonium tetrafluoroborates. The title compounds are obtained in up to 99 % yield and 96 % ee. The air‐ and water‐tolerant reaction allows electronic and steric diversity of the aryldiazonium electrophile and the tryptamine core.
Evaluation of new chemically modified coconut shell adsorbents with tannic acid for Cu (II) removal from wastewater
Authors: de Oliveira Sousa Neto Vicente , Melo Diego Quadros , de Oliveira Talles Cardoso , Nonato Raimundo , Teixeira P. , Silva Marcos Antônio Araújo , Nascimento Ronaldo Ferreira do
Published: April 2014

The adsorption of Cu (II) from aqueous solutions using coconut shell modified powder was investigated in batch experiments. The surface charge of the adsorbent was determined. The points of zero charge (PZC) of the adsorbents (pHPZC) were 4.5, 2.0, and 2.0 to raw coconut (RC), raw coconut alkalized (RCA), and coconut shell modified with tannic acid (TCA) adsorbent, respectively. Batch experiments were performed under kinetic and equilibrium conditions. The kinetic data were analyzed using a pseudo second‐order, and Elovich equation. Adsorption equilibrium data were investigated using the Langmiur, Freundlich, Temkin, and Dubinin–Raduschevich (D–R) isotherm models. It has been found that chemically modified coconut shell (TAC) affected performance when compared with unmodified coconut shell (RC). Kinetic studies showed that the adsorption followed a pseudo‐second‐order rate model. Biosorption kinetics of Cu(II) on the adsorbent TCA was rapid such that almost 90% of Cu(II) were adsorbed within 80 min. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40744.
The greater scattering phenomenon beyond Bradford's law in patent citation
Authors: Huang Mu‐Hsuan , Huang Wei‐Tzu , Chang Cheng‐Ching , Chen Dar‐Zen , Lin Chang‐Pin
Published: April 2014

Patent analysis has become important for management as it offers timely and valuable information to evaluate R&D performance and identify the prospects of patents. This study explores the scattering patterns of patent impact based on citations in 3 distinct technological areas, the liquid crystal, semiconductor, and drug technological areas, to identify the core patents in each area. The research follows the approach from Bradford's law, which equally divides total citations into 3 zones. While the result suggests that the scattering of patent citations corresponded with features of Bradford's law, the proportion of patents in the 3 zones did not match the proportion as proposed by the law. As a result, the study shows that the distributions of citations in all 3 areas were more concentrated than what Bradford's law proposed. The Groos (1967) droop was also presented by the scattering of patent citations, and the growth rate of cumulative citation decreased in the third zone.
Measuring excellence in Russia: Highly cited papers, leading institutions, patterns of national and international collaboration
Authors: Pislyakov Vladimir , Shukshina Elena
Published: April 2014

In this study, we discover Russian “centers of excellence” and explore patterns of their collaboration with each other and with foreign partners. Highly cited papers serve as a proxy for “excellence” and coauthored papers as a measure of collaborative efforts. We find that currently research institutes (of the Russian Academy of Sciences as well as others) remain the key players despite recent government initiatives to stimulate university science. The contribution of the commercial sector to high‐impact research is negligible. More than 90% of Russian highly cited papers involve international collaboration, and Russian institutions often do not play a dominant role. Partnership with U.S., German, U.K., and French scientists increases markedly the probability of a Russian paper becoming highly cited. Patterns of national (“intranational”) collaboration in world‐class research differ significantly across different types of organizations; the strongest ties are between three nuclear/particle physics centers. Finally, we draw a coauthorship map to visualize collaboration between Russian centers of excellence.
Analyzing broken links on the web of data: An experiment with DBpedia
Authors: Rajabi Enayat , Sanchez‐Alonso Salvador , Sicilia Miguel‐Angel
Published: April 2014

Linked open data allow interlinking and integrating any kind of data on the web. Links between various data sources play a key role insofar as they allow software applications (e.g., browsers, search engines) to operate over the aggregated data space as if it was a unique local database. In this new data space, where DBpedia, a data set including structured information from Wikipedia, seems to be the central hub, we analyzed and highlighted outgoing links from this hub in an effort to discover broken links. The paper reports on an experiment to examine the causes of broken links and proposes some treatments for solving this problem.
Adaptive data fusion methods in information retrieval
Authors: Wu Shengli , Li Jieyu , Zeng Xiaoqin , Bi Yaxin
Published: April 2014

Data fusion is currently used extensively in information retrieval for various tasks. It has proved to be a useful technology because it is able to improve retrieval performance frequently. However, in almost all prior research in data fusion, static search environments have been used, and dynamic search environments have generally not been considered. In this article, we investigate adaptive data fusion methods that can change their behavior when the search environment changes. Three adaptive data fusion methods are proposed and investigated. To test these proposed methods properly, we generate a benchmark from a historic Text REtrieval Conference data set. Experiments with the benchmark show that 2 of the proposed methods are good and may potentially be used in practice.
Research on tables and graphs in academic articles: Pitfalls and promises
Authors: Hartley James , Cabanac Guillaume , Kozak Marcin , Hubert Gilles
Published: April 2014

Many papers have appeared recently assessing the effects of using tables and graphs in scientific publications. In this brief communication, we assess some of the methodological difficulties that have arisen in this context. These difficulties encompass issues of data availability, suitability of indicators, nature and purpose of tables and graphs, and the role of supplementary information.
Long‐term changes in Australian tropical cyclone numbers
Authors: Dowdy Andrew J.
Published: April 2014

Tropical cyclone (TC) observations are used to examine changes in the TC climatology of the Australian region. The ability to investigate long‐term changes in TC numbers improves when the El Niño‐Southern Oscillation (ENSO) is considered. Removing variability in TC numbers associated with ENSO shows a significant decreasing trend in TC numbers at the 93–98% confidence level. Additionally, there is some indication of a temporal change in the relationship between ENSO and TC numbers, with ENSO accounting for about 35–50% of the variance in TC numbers during the first half of the study period, but only 10% during the second half.
Dual roles for autophagy: Degradation and secretion of Alzheimer's disease Aβ peptide
Authors: Nilsson Per , Saido Takaomi C.
Published: April 2014

Alzheimer's disease (AD) is a neurodegenerative disease exhibiting amyloid beta (Aβ) peptide accumulation as a key characteristic. Autophagy, which is dysregulated in AD, participates in the metabolism of Aβ. Unexpectedly, we recently found that autophagy, in addition to its degradative function, also mediates the secretion of Aβ. This finding adds Aβ to an increasing number of biomolecules, the secretion of which is mediated by autophagy. We also showed that inhibition of Aβ secretion through genetic deletion of autophagy leads to intracellular Aβ accumulation, which enhanced neurodegeneration induced by autophagy deficiency. Hence, autophagy may play a central role in two pathological hallmarks of AD: Aβ amyloidosis and neurodegeneration. Herein, we summarize the role of autophagy in AD with focus on Aβ metabolism in light of the recently established role of autophagy in protein secretion. We discuss potential routes for autophagy‐mediated Aβ secretion and suggest experimental approaches to further elucidate its mechanisms.
Morbidity in early Parkinson's disease and prior to diagnosis
Authors: Frandsen Rune , Kjellberg Jakob , Ibsen Rikke , Jennum Poul
Published: April 2014

Background

Nonmotor symptoms are probably present prior to, early on, and following, a diagnosis of Parkinson's disease. Nonmotor symptoms may hold important information about the progression of Parkinson's disease.

Objective

To evaluated the total early and prediagnostic morbidities in the 3 years before a hospital contact leading to a diagnosis of Parkinson's disease.

Methods

Retrospective morbidity data from Danish National Patient Registry records (1997–2007) of 10,490 adult patients with a secondary care diagnosis of Parkinson's disease were compared with 42,505 control cases.

Results

Parkinson's disease was associated with significantly higher morbidity rates associated with conditions in the following categories: mental and psychiatric, nervous system, gastrointestinal, musculoskeletal system and connective tissue, genitourinary, abnormal clinical and laboratory findings, injury, poisoning and certain other external causes, and other factors influencing health status and contact with health services. It was negatively associated with neoplasm, cardiovascular, and respiratory diseases.

Conclusions

Patients with a diagnosis of Parkinson's disease present significant differences in morbidities early on, following, and prior to, their diagnosis, compared with healthy controls.
X: A Case Study of a Swedish Neo‐Nazi and His Reintegration into Swedish Society
Authors: Stern Jessica Eve
Published: April 2014

This article provides a case study of a Swedish neo‐Nazi and the reintegration program being provided to him. During an extensive interview that took place over two days, he told a researcher that he was interested in having a violent adventure, and that he was drawn to Nazi symbols and history more than their creed. In comparison with ordinary crime, terrorist crime is quite rare, and access to detailed case studies is rarer still, making the development of a prospective risk‐assessment instrument extremely difficult. Researchers' “thick descriptions” of their encounters with terrorists can help us to develop putative risk factors which can then be tested against controls. The article concludes by arguing that just as there is no single pathway into or out of terrorism, there can be no single reintegration program. A series of thick descriptions is a first step toward understanding what leads individuals into and out of terrorism. Copyright © 2014 John Wiley & Sons, Ltd.
Epidemiological survey of suicide ideation and acts and other deliberate self‐harm among offenders in the community under supervision of the Probation Service in England and Wales
Authors: Pluck Graham , Brooker Charlie
Published: April 2014

Background

There is a dearth of information on suicidal thoughts and acts or other acts of deliberate self‐harm by offenders under community supervision.

Aims

The objective of this study is to estimate lifetime and one month prevalence of deliberate self‐harm and to determine ongoing risk among offenders in the community under probation supervision.

Methods

One hundred and seventy‐three randomly selected offenders under supervision by the probation service in one county in England were screened for mental illness. All 88 screened cases and a one‐in‐five sample of non‐cases were interviewed according to the Mini International Neuropsychiatric Inventory Module‐B. False negatives (n = 17) were used to weight calculations and estimate prevalence for the whole group.

Results

A third of the interviewed sample (n = 56) had a lifetime history of suicide attempts, and 9 (5%) had self‐harmed in the month prior to interview. Lifetime suicide history was associated with suicidal ideation and deliberate self‐harm in the prior month.

Conclusions and implications

Our adjusted findings indicate that 25‐40% of offenders serving all or part of their sentence in the community have a lifetime history of self‐harm, which is similar to the rate among prisoners, and are at very much higher risk of further such acts or completed suicide than the general population. At a time of change in delivery of probation services the implications are that

rates of suicide and other forms of deliberate self‐harm should be continually assessed in all probation areas, particularly with reference to service changes;

the relationship between deliberate acts of self‐harm, suicidal ideation and completion of suicide should be investigated prospectively in larger studies;

probation services are likely to need mental health expertise to manage these risks Copyright © 2014 John Wiley & Sons, Ltd.
The Enhancing Effect of Brønsted Acidity of Supported MoOx Species on their Activity and Selectivity in Ethylene/trans‐2‐Butene Metathesis
Authors: Hahn Tobias , Bentrup Ursula , Armbrüster Marc , Kondratenko Evgenii V. , Linke David
Published: April 2014

Supported catalysts with a nominal Mo surface density of 0.15 and 1.5 Mo atoms nm−2 were synthesized by impregnation of alumina, silica, and alumina–silica supports with silica content between 1 and 70 wt %. They were tested for their activity and selectivity in the metathesis of ethylene and trans‐2‐butene to propene between 343 and 603 K at 125 kPa. The catalysts were characterized by UV/Vis, Raman, and IR spectroscopy, XRD and H2 temperature‐programmed reduction for elucidating the distribution, degree of polymerization, reducibility, and acidity of MoOx species. We established that Brønsted acidity of highly dispersed tetrahedral and polymerized octahedral MoOx species is required to ensure high metathesis activity. The acidic character of these species is influenced by their structure and support. Tetrahedral MoOx species with Brønsted acidic character are only formed on supports possessing such acidity, whereas Brønsted acidic octahedral MoOx is also created on supports without such acidic sites.
Substrate‐Dependent H/D Kinetic Isotope Effects and the Role of the Di(μ‐oxo)diiron(IV) Core in Soluble Methane Monooxygenase: A Theoretical Study
Authors: Mai Binh Khanh , Kim Yongho
Published: April 2014

Soluble methane monooxygenase (sMMO) is an enzyme that converts alkanes to alcohols using a di(μ‐oxo)diiron(IV) intermediate Q at the active site. Very large kinetic isotope effects (KIEs) indicative of significant tunneling are observed for the hydrogen transfer (H‐transfer) of CH4 and CH3CN; however, a relatively small KIE is observed for CH3NO2. The detailed mechanism of the enzymatic H‐transfer responsible for the diverse range of KIEs is not yet fully understood. In this study, variational transition‐state theory including the multidimensional tunneling approximation is used to calculate rate constants to predict KIEs based on the quantum‐mechanically generated intrinsic reaction coordinates of the H‐transfer by the di(μ‐oxo)diiron(IV) complex. The results of our study reveal that the role of the di(μ‐oxo)diiron(IV) core and the H‐transfer mechanism are dependent on the substrate. For CH4, substrate binding induces an electron transfer from the oxygen to one FeIV center, which in turn makes the μ‐O ligand more electrophilic and assists the H‐transfer by abstracting an electron from the CH σ orbital. For CH3CN, the reduction of FeIV to FeIII occurs gradually with substrate binding and H‐transfer. The charge density and electrophilicity of the μ‐O ligand hardly change upon substrate binding; however, for CH3NO2, there seems to be no electron movement from μ‐O to FeIV during the H‐transfer. Thus, the μ‐O ligand appears to abstract a proton without an electron from the CH σ orbital. The calculated KIEs for CH4, CH3CN, and CH3NO2 are 24.4, 49.0, and 8.27, respectively, at 293 K, in remarkably good agreement with the experimental values. This study reveals that diverse KIE values originate mainly from tunneling to the same di(μ‐oxo)diiron(IV) core for all substrates, and demonstrate that the reaction dynamics are essential for reproducing experimental results and understanding the role of the diiron core for methane oxidation in sMMO.
4,4′‐Bipyridine as a Unidirectional Switching Unit for a Molecular Pushing Motor
Authors: Kallweit Christine , Haberhauer Gebhard , Woitschetzki Sascha
Published: April 2014

A chirality switch in which the intrinsic chirality of a 4,4′‐bipyridine is combined with a metal‐ion‐induced switching principle is described. In the uncomplexed state the 4,4′‐bipyridine unit, which is linked to an S,S,S,S‐configured cyclic imidazole peptide, is P‐configured. The addition of zinc ions leads to a rotation around the CC bond axis of the 4,4′‐bipyridine and the M isomer of the metal complex is formed. By addition of a stronger complexing agent the metal ions are removed and the switch returns to its initial position. The combination of the chirality switch with a second switching unit allows the construction of a molecular pushing motor, which is driven chemically and by light.
A Theoretical Investigation into the Luminescent Properties of d8‐Transition‐Metal Complexes with Tetradentate Schiff Base Ligands
Authors: Tong Glenna So Ming , Chow Pui Keong , To Wai‐Pong , Kwok Wai‐Ming , Che Chi‐Ming
Published: April 2014

A theoretical investigation on the luminescence efficiency of a series of d8 transition‐metal Schiff base complexes was undertaken. The aim was to understand the different photophysics of [M‐salen]n complexes (salen=N,N′‐bis(salicylidene)ethylenediamine; M=Pt, Pd (n=0); Au (n=+1)) in acetonitrile solutions at room temperature: [Pt‐salen] is phosphorescent and [Au‐salen]+ is fluorescent, but [Pd‐salen] is nonemissive. Based on the calculation results, it was proposed that incorporation of electron‐withdrawing groups at the 4‐position of the Schiff base ligand should widen the 3MLCT–3MC gap (MLCT=metal‐to‐ligand charge transfer and MC=metal centered, that is, the dd excited state); thus permitting phosphorescence of the corresponding PdII Schiff base complex. Although it is experimentally proven that [Pd‐salph‐4E] (salph=N,N′‐bis(salicylidene)‐1,2‐phenylenediamine; 4E means an electron‐withdrawing substituent at the 4‐position of the salicylidene) displays triplet emission, its quantum yield is low at room temperature. The corresponding PtII Schiff base complex, [Pt‐salph‐4E], is also much less emissive than the unsubstituted analogue, [Pt‐salph]. Thus, a detailed theoretical analysis of how the substituent and central metal affected the photophysics of [M‐salph‐X] (X is a substituent on the salph ligand, M=Pt or Pd) was performed. Temperature effects were also investigated. The simple energy gap law underestimated the nonradiative decay rates and was insufficient to account for the temperature dependence of the nonradiative decay rates of the complexes studied herein. On the other hand, the present analysis demonstrates that inclusions of low‐frequency modes and the associated frequency shifts are decisive in providing better quantitative estimates of the nonradiative decay rates and the experimentally observed temperature effects. Moreover, spin–orbit coupling, which is often considered only in the context of radiative decay rate, has a significant role in determining the nonradiative rate as well.
Metal–Ligand Cooperation on a Diruthenium Platform: Selective Imine Formation through Acceptorless Dehydrogenative Coupling of Alcohols with Amines
Authors: Saha Biswajit , Wahidur Rahaman S. M. , Daw Prosenjit , Sengupta Gargi , Bera Jitendra K.
Published: April 2014

Metalmetal singly‐bonded diruthenium complexes, bridged by naphthyridine‐functionalized N‐heterocyclic carbene (NHC) ligands featuring a hydroxy appendage on the naphthyridine unit, are obtained in a single‐pot reaction of [Ru2(CH3COO)2(CO)4] with 1‐benzyl‐3‐(5,7‐dimethyl‐1,8‐naphthyrid‐2‐yl)imidazolium bromide (BIN⋅HBr) or 1‐isopropyl‐3‐(5,7‐dimethyl‐1,8‐naphthyrid‐2‐yl)imidazolium bromide (PIN⋅HBr), TlBF4, and substituted benzaldehyde containing an electron‐withdrawing group. The modified NHC‐naphthyridine‐hydroxy ligand spans the diruthenium unit in which the NHC carbon and hydroxy oxygen occupy the axial sites. All the synthesized compounds catalyze acceptorless dehydrogenation of alcohols to the corresponding aldehydes in the presence of a catalytic amount of weak base 1,4‐diazabicyclo[2.2.2]octane (DABCO). Further, acceptorless dehydrogenative coupling (ADHC) of the alcohol with amines affords the corresponding imine as the sole product. The substrate scope is examined with 1 (BIN, p‐nitrobenzaldehyde). A similar complex [Ru2(CO)4(CH3COO)(3‐PhBIN)][Br], that is devoid of a hydroxy arm, is significantly less effective for the same reaction. Neutral complex 1 a, obtained by deprotonation of the hydroxy arm in 1, is found to be active for the ADHC of alcohols and amines under base‐free conditions. A combination of control experiments, deuterium labeling, kinetic Hammett studies, and DFT calculations support metal–hydroxyl/hydroxide and metal–metal cooperation for alcohol activation and dehydrogenation. The bridging acetate plays a crucial role in allowing β‐hydride elimination to occur. The ligand architecture on the diruthenium core causes rapid aldehyde extrusion from the metal coordination sphere, which is responsible for exclusive imine formation.
Molecular Engineering of Simple Phenothiazine‐Based Dyes To Modulate Dye Aggregation, Charge Recombination, and Dye Regeneration in Highly Efficient Dye‐Sensitized Solar Cells
Authors: Hua Yong , Chang Shuai , He Jian , Zhang Caishun , Zhao Jianzhang , Chen Tao , Wong Wai‐Yeung , Wong Wai‐Kwok , Zhu Xunjin
Published: April 2014

A series of simple phenothiazine‐based dyes, namely, TP, EP, TTP, ETP, and EEP have been developed, in which the thiophene (T), ethylenedioxythiophene (E), their dimers, and mixtures are present to modulate dye aggregation, charge recombination, and dye regeneration for highly efficient dye‐sensitized solar cell (DSSC) applications. Devices sensitized by the dyes TP and TTP display high power conversion efficiencies (PCEs) of 8.07 (Jsc=15.2 mA cm−2, Voc=0.783 V, fill factor (FF)=0.679) and 7.87 % (Jsc=16.1 mA cm−2, Voc=0.717 V, FF=0.681), respectively; these were measured under simulated AM 1.5 sunlight in conjunction with the I−/I3− redox couple. By replacing the T group with the E unit, EP‐based DSSCs had a slightly lower PCE of 7.98 % with a higher short‐circuit photocurrent (Jsc) of 16.7 mA cm−2. The dye ETP, with a mixture of E and T, had an even lower PCE of 5.62 %. Specifically, the cell based on the dye EEP, with a dimer of E, had inferior Jsc and Voc values and corresponded to the lowest PCE of 2.24 %. The results indicate that the photovoltaic performance can be finely modulated through structural engineering of the dyes. The selection of T analogues as donors can not only modulate light absorption and energy levels, but also have an impact on dye aggregation and interfacial charge recombination of electrons at the interface of titania, electrolytes, and/or oxidized dye molecules; this was demonstrated through DFT calculations, electrochemical impedance analysis, and transient photovoltage studies.
Two‐Step Functionalization of Oligosaccharides Using Glycosyl Iodide and Trimethylene Oxide and Its Applications to Multivalent Glycoconjugates
Authors: Hsieh Hsiao‐Wu , Davis Ryan A. , Hoch Jessica A. , Gervay‐Hague Jacquelyn
Published: April 2014

Oligosaccharide conjugates, such as glycoproteins and glycolipids, are potential chemotherapeutics and also serve as useful tools for understanding the biological roles of carbohydrates. With many modern isolation and synthetic technologies providing access to a wide variety of free sugars, there is increasing need for general methodologies for carbohydrate functionalization. Herein, we report a two‐step methodology for the conjugation of per‐O‐acetylated oligosaccharides to functionalized linkers that can be used for various displays. Oligosaccharides obtained from both synthetic and commercial sources were converted to glycosyl iodides and activated with I2 to form reactive donors that were subsequently trapped with trimethylene oxide to form iodopropyl conjugates in a single step. The terminal iodide served as a chemical handle for further modification. Conversion into the corresponding azide followed by copper‐catalyzed azide–alkyne cycloaddition afforded multivalent glycoconjugates of Gb3 for further investigation as anti‐cancer therapeutics.
Expedient Iron‐Catalyzed Coupling of Alkyl, Benzyl and Allyl Halides with Arylboronic Esters
Authors: Bedford Robin B. , Brenner Peter B. , Carter Emma , Carvell Thomas W. , Cogswell Paul M. , Gallagher Timothy , Harvey Jeremy N. , Murphy Damien M. , Neeve Emily C. , Nunn Joshua , Pye Dominic R.
Published: April 2014

While attractive, the iron‐catalyzed coupling of arylboron reagents with alkyl halides typically requires expensive or synthetically challenging diphosphine ligands. Herein, we show that primary and secondary alkyl bromides and chlorides, as well as benzyl and allyl halides, can be coupled with arylboronic esters, activated with alkyllithium reagents, by using very simple iron‐based catalysts. The catalysts used were either adducts of inexpensive and widely available diphosphines or, in a large number of cases, simply [Fe(acac)3] with no added co‐ ligands. In the former case, preliminary mechanistic studies highlight the likely involvement of iron(I)–phosphine intermediates.
Unfolding and Conformational Variations of Thrombin‐Binding DNA Aptamers: Synthesis, Circular Dichroism and Molecular Dynamics Simulations
Authors: Sun Lidan , Jin Hongwei , Zhao Xiaoyang , Liu Zhenming , Guan Yifu , Yang Zhenjun , Zhang Liangren , Zhang Lihe
Published: April 2014

Thrombin‐binding DNA aptamer (TBA), with a consensus 15‐base sequence: d(GGTTGGTGTGGTTGG), can fold into an antiparallel unimolecular G‐quadruplex structure that is necessary for its interaction with thrombin. For the first time, using steered molecular dynamics (SMD) simulations, we have successfully simulated the unfolding process of native TBA G‐quadruplex. The unfolding pathway proposed is in agreement with previously reported experimental NMR data. Moreover, the critical intermediate structure in the unfolding pathway, predicted by the NMR results, was identified. The structural characteristics of several TBA oligonucleotides modified with locked nucleoside (LNA) or 2′‐O‐methyl‐nucleoside (MNA) at different positions and number were also investigated by CD spectroscopy. An oligonucleotide substituted with either LNA or MNA at position 2 folds into a native‐like G‐quadruplex, while doubly substituted derivatives of TBA where LNA or MNA is incorporated at positions 11 and 14 are no longer able to form a G‐quadruplex. Starting from the same initial intermediate structure, we successfully overcame sampling limitations, and simulated the large conformational variations in structures of native TBA and modified TBAs by classic MD. Analysis of the models showed that inversion of the glycosyl orientation at position 14 contributes significantly to the disruption of G‐quadruplex formation in both of the di‐substituted modified TBA systems. Our calculations provide a simple and reliable theoretical model that can be used to investigate and predict the effects of the modifications of an oligonucleotide on the resultant G‐quadruplex structure. In addition, the computational protocol described can also be applied for other G‐quadruplex systems.
trans,cis,cis‐Bis(benzoato)dichlorido(cyclohexane‐1R,2R‐diamine)platinum(IV): a Prodrug Candidate for the Treatment of Oxaliplatin‐Refractory Colorectal Cancer
Authors: Gandin Valentina , Marzano Cristina , Pelosi Giorgio , Ravera Mauro , Gabano Elisabetta , Osella Domenico
Published: April 2014

The gold standard for the treatment of metastatic colorectal cancer consists of combination chemotherapy. Over time, however, the development of chemoresistant tumor clones leads to relapse. It may be possible to overcome oxaliplatin chemoresistance in colorectal cancer cells by exploiting a complex obtained from the insertion of the cyclohexane‐1R,2R‐diamine carrier ligand (the same diamine present in oxaliplatin) into an octahedral PtIV scaffold with high lipophilicity conferred by two benzoate axial ligands. Herein we report the synthesis, characterization (including X‐ray structure), biological activity, and cellular accumulation of trans,cis,cis‐bis(benzoato)dichlorido(cyclohexane‐1R,2R‐diamine)platinum(IV) complex in a panel of several human cancer cell lines, including a colon carcinoma cell line resistant to oxaliplatin. The compound under investigation shows the best performance in terms of in vitro anti‐proliferative activity and ability to overcome chemoresistance, with respect to oxaliplatin and some other PtII reference complexes. This result is likely related to the high lipophilicity shown by the title compound that favors its cellular accumulation by passive diffusion.
Experiences building Globus Genomics: a next‐generation sequencing analysis service using Galaxy, Globus, and Amazon Web Services
Authors: Madduri Ravi K. , Sulakhe Dinanath , Lacinski Lukasz , Liu Bo , Rodriguez Alex , Chard Kyle , Dave Utpal J. , Foster Ian T.
Published: April 2014

We describe Globus Genomics, a system that we have developed for rapid analysis of large quantities of next‐generation sequencing genomic data. This system achieves a high degree of end‐to‐end automation that encompasses every stage of data analysis including initial data retrieval from remote sequencing centers or storage (via the Globus file transfer system); specification, configuration, and reuse of multistep processing pipelines (via the Galaxy workflow system); creation of custom Amazon Machine Images and on‐demand resource acquisition via a specialized elastic provisioner (on Amazon EC2); and efficient scheduling of these pipelines over many processors (via the HTCondor scheduler). The system allows biomedical researchers to perform rapid analysis of large next‐generation sequencing datasets in a fully automated manner, without software installation or a need for any local computing infrastructure. We report performance and cost results for some representative workloads. Copyright © 2014 John Wiley & Sons, Ltd.
Thermodynamics and 2H NMR Study on the Insertion of Small Quinones into a Discotic Nematic Lyotropic Liquid Crystal
Authors: Bahamonde‐Padilla Víctor Eduardo , López‐Cascales José Javier , Araya‐Maturana Ramiro , Martínez‐Cifuentes Maximiliano , Weiss López Boris Enrique
Published: April 2014

A detailed description of the distribution, interaction, and dynamics of molecules with biological activity dissolved in a hydrophobic bilayer, a simple model of a biological membrane, provides valuable information for a better understanding of drug functioning, which can be very useful in drug design. Here we present an 2H NMR and molecular dynamics study on the insertion, distribution, interactions, and thermodynamics of two biologically active molecules, 9,10‐dihydroxy‐4,4‐dimethyl‐1,4,5,8‐tetrahydroanthracen‐1‐one (HQ), with anticancer activity, and 4,4‐dimethyl‐1,4,5,8,9,10‐hexahydroanthracen‐1,9,10‐trione (Q) a fungicide, dissolved in a nematic discotic lyotropic liquid crystal (ndllc) composed of sodium dodecylsulphate (SDS), decanol (DecOH) and Na2SO4 in water. 2H NMR quadrupole splittings (ΔνQ) and longitudinal relaxation times (T1) from HQ‐d6, Q‐d4, DecOH‐α‐d2, partially deuterated water, and SDS‐d25 were measured and several molecular dynamics trajectories were also calculated. In particular, ΔG, ΔH, and ΔS profiles for the process of both molecules crossing the bilayer were estimated. It was evidenced that the insertion of both molecules into the aggregate is a spontaneous process, and the molecules are mainly distributed in the internal side of the interface. Addition of HQ or Q decreased the mobility of all aggregate components, but this effect was more pronounced for HQ. The rotational correlation time of Q allowed an estimate of 5.3 cP for the microviscosity inside the ndllc aggregate, in the order of previously measured values in similar environments. Both guest molecules display similar free‐energy profiles for the process of crossing the bilayer, with a calculated barrier height of 25 and 36 kJ mol−1 for HQ and Q, respectively.
Effect of Nanoscale Confinement on Freezing of Modified Water at Room Temperature and Ambient Pressure
Authors: Deshmukh Sanket , Kamath Ganesh , Sankaranarayanan Subramanian K. R. S.
Published: April 2014

Understanding the phase behavior of confined water is central to fields as diverse as heterogeneous catalysis, corrosion, nanofluidics, and to emerging energy technologies. Altering the state points (temperature, pressure, etc.) or introduction of a foreign surface can result in the phase transformation of water. At room temperature, ice nucleation is a very rare event and extremely high pressures in the GPa–TPa range are required to freeze water. Here, we perform computer experiments to artificially alter the balance between electrostatic and dispersion interactions between water molecules, and demonstrate nucleation and growth of ice at room temperature in a nanoconfined environment. Local perturbations in dispersive and electrostatic interactions near the surface are shown to provide the seed for nucleation (nucleation sites), which lead to room temperature liquid–solid phase transition of confined water. Crystallization of water occurs over several tens of nanometers and is shown to be independent of the nature of the substrate (hydrophilic oxide vs. hydrophobic graphene and crystalline oxide vs. amorphous diamond‐like carbon). Our results lead us to hypothesize that the freezing transition of confined water can be controlled by tuning the relative dispersive and electrostatic interaction.
Syntheses of Functionalized Allylamines via Lithiated Intermediates
Authors: Firdous Samia , Kazmaier Uli
Published: April 2014

Lithiated allylamines are easily available by tin–lithium exchange from stannylated allylamines and are suitable nucleophiles for a wide range of conversions. With aldehydes and ketones, aminomethylated allyl alcohols are formed, whereas the reaction with α‐brominated ketones gives rise to vinyl epoxides or aldehydes, depending on the reaction and workup conditions used.
Synthesis and Selected Reactivity Studies of a Dissymmetric (Phosphinoylmethylpyridine N‐Oxide) Methylamine Platform
Authors: Ouizem Sabrina , Pailloux Sylvie L. , Ray Alisha D. , Duesler Eileen N. , Dickie Diane A. , Paine Robert T. , Hay Benjamin P.
Published: April 2014

Efficient syntheses for the precursor molecules, 2‐{6‐[((diphenylphosphoryl)methyl)pyridin‐2‐yl]methyl}isoindoline‐1,3‐dione (2), 2‐[(1,3‐dioxoisoindolin‐2‐yl)methyl]‐6‐[(diphenylphosphoryl)methyl]pyridine 1‐oxide (3), and their 6‐[bis(2‐(trifluoromethyl)phenyl)phosphoryl]methyl analogues are reported along with their transformations into the dissymmetric ligands, [(6‐(aminomethyl)pyridin‐2‐yl)methyl]diphenylphosphine oxide (4), 2‐(aminomethyl)‐6‐[(diphenylphosphoryl)methyl]pyridine 1‐oxide (5) and 2‐(aminomethyl)‐6‐{[bis(2‐(trifluoromethyl)phenyl)phosphoryl]methyl}pyridine 1‐oxide (5‐F). Selected reactivity of the aminomethyl substituent of 4 and 5, as well as complexation reactions of several of the compounds with lanthanide(III) ions are described. Molecular structures of three uniquely different complexes, {Pr{2‐[HC(O)N(H)CH2]‐6‐[Ph2P(O)CH2]C5H3NO}(NO3)3(MeOH)}2, {Eu{2‐[(Me2N)2CN(H+)CH2]‐6‐[Ph2P(O)CH2]C5H3N(H)+}(NO3)4(OMe)} and {Er{2‐[(C8H4O2)NCH2]‐6‐[Ph2P(O)CH2]C5H3N(O)}(NO3)3(MeOH)}·(CH3)2CO, have been determined by single‐crystal X‐ray diffraction methods. The observed and computationally modeled structures that employ bidentate and tridentate ligand/metal interactions are compared. These results suggest further ligand modifications that should provide improved solvent extraction reagents.
In Situ Evaluation of the Anticancer Antibody Rituximab‐dsDNA Interaction Using a DNA‐Electrochemical Biosensor
Authors: Santarino Inês B. , Oliveira Severino Carlos B. , Oliveira‐Brett Ana Maria
Published: April 2014

A multilayer dsDNA‐electrochemical biosensor for the in situ electrochemical evaluation of anticancer antibody rituximab (RTX) interaction with double‐stranded DNA (dsDNA), with differential pulse voltammetry was used. The decrease of the dsDNA oxidation peaks with incubation time was observed and was confirmed that RTX binds causing dsDNA condensation, and no evidence for DNA base oxidative damage was detected electrochemically. Nondenaturing agarose gel‐electrophoresis of RTX‐dsDNA samples confirmed the occurrence of condensation in the dsDNA structure.
Ultrasensitive and Simple Method for Determination of N‐Acetyl‐L‐Cysteine in Drug Formulations Using a Diamond Sensor
Authors: Nantaphol Siriwan , Chailapakul Orawon , Siangproh Weena
Published: April 2014

A boron‐doped diamond (BDD) electrode coupled to flow injection analysis (FIA) was firstly developed for determination of N‐acetyl‐L‐cysteine (NAC) in drug formulations. The effects of experimental parameters including pH, applied potential and scan rate on the response were investigated. FIA amperometry was applied as an automatic method for the quantitative detection of trace amounts of NAC. A wide linear range of 0.5–50 µmol/L and a low detection limit of 10 nmol/L were obtained. The results of amperometric determinations show a very good reproducibility, and the RSD for the measurement based on 10 measurements was <3.7 % and <4.1 % for intra‐ and inter‐day, respectively. The benefits of the proposed method are fast, simple, sensitive and no requirement of complicated operational steps.
Local acting Sticky‐trap inhibits vascular endothelial growth factor dependent pathological angiogenesis in the eye
Authors: Michael Iacovos P , Westenskow Peter D , Hacibekiroglu Sabiha , Greenwald Alissa Cohen , Ballios Brian G , Kurihara Toshihide , Li Zhijie , Warren Carmen M , Zhang Puzheng , Aguilar Edith , Donaldson Laura , Marchetti Valentina , Baba Takeshi , Hussein Samer M , Sung Hoon‐Ki , Iruela‐Arispe M Luisa , Rini James M , van der Kooy Derek , Friedlander Martin , Nagy Andras
Published: April 2014

Current therapeutic antiangiogenic biologics used for the treatment of pathological ocular angiogenesis could have serious side effects due to their interference with normal blood vessel physiology. Here, we report the generation of novel antivascular endothelial growth factor‐A (VEGF) biologics, termed VEGF “Sticky‐traps,” with unique properties that allow for local inhibition of angiogenesis without detectable systemic side effects. Using genetic and pharmacological approaches, we demonstrated that Sticky‐traps could locally inhibit angiogenesis to at least the same extent as the original VEGF‐trap that also gains whole‐body access. Sticky‐traps did not cause systemic effects, as shown by uncompromised wound healing and normal tracheal vessel density. Moreover, if injected intravitreally, recombinant Sticky‐trap remained localized to various regions of the eye, such as the inner‐limiting membrane and ciliary body, for prolonged time periods, without gaining access either to the photoreceptors/choriocapillaris area or the circulation. These unique pharmacological characteristics of Sticky‐trap could allow for safe treatment of pathological angiogenesis in patients with diabetic retinopathy and retinopathy of pre‐maturity.
Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3
Authors: Khan Nahid A , Auranen Mari , Paetau Ilse , Pirinen Eija , Euro Liliya , Forsström Saara , Pasila Lotta , Velagapudi Vidya , Carroll Christopher J , Auwerx Johan , Suomalainen Anu
Published: April 2014

Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD+/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD+ precursor, was previously shown to boost NAD+ levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early‐ and late‐stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD+ levels are a promising treatment strategy for mitochondrial myopathy.
Effect of Annealing Temperature of ZnO on the Energy Level Alignment in Inverted Organic Photovoltaics (OPVs)
Authors: Sharma Anirudh , Watkins Scott E. , Andersson Gunther , Lewis David A.
Published: April 2014

The annealing temperature of zinc oxide (ZnO) layers was found to have a significant impact on the efficiency of inverted devices. Device efficiencies were found to increase significantly from 2.5 % to 3.6 % with an increase in the post‐deposition annealing temperature of ZnO. A systematic study of the density of states shows that the work function varies from 3.2 to 3.9 eV with annealing temperature and the offset between the conduction band of ZnO and the lowest unoccupied molecular orbital (LUMO) of the [6,6]‐phenyl‐C61‐butyric acid methyl ester (PCBM) reduced from 0.5 eV (250 °C annealing) to 0 eV (150 °C annealing) resulting in inefficient charge transport across the bulk heterojunction (BHJ) to the indium tin oxide (ITO) electrode. The dependence of the electronic properties on the annealing temperature has been attributed to a deficiency of electrons corresponding to the nonbonding (lone pair) oxygen orbitals in the ZnO matrix and the presence of precursor impurities.
The Development of Visible‐Light Photoredox Catalysis in Flow
Authors: Garlets Zachary J. , Nguyen John D. , Stephenson Corey R. J.
Published: April 2014

Visible‐light photoredox catalysis has recently emerged as a viable alternative for radical reactions otherwise carried out with tin and boron reagents. It has been recognized that by merging photoredox catalysis with flow chemistry, slow reaction times, lower yields, and safety concerns may be obviated. While flow reactors have been successfully applied to reactions carried out with UV light, only recent developments have demonstrated the same potential of flow reactors for the improvement of visible‐light‐mediated reactions. This review examines the initial and continuing development of visible‐light‐mediated photoredox flow chemistry by exemplifying the benefits of flow chemistry compared with conventional batch techniques.
Molecular Dynamics Simulations of Bromodomains Reveal Binding‐Site Flexibility and Multiple Binding Modes of the Natural Ligand Acetyl‐Lysine
Authors: Spiliotopoulos Dimitrios , Caflisch Amedeo
Published: April 2014

Experimental protein structures provide spatial information at the atomic level. A further dimension, time, is supplemented by molecular dynamics. Since the pioneering work on the 58‐residue inhibitor of bovine pancreatic trypsin in the group of Martin Karplus in the seventies, molecular dynamics simulations have shown that the intrinsic flexibility of proteins is essential for their function. Here, we review simulation studies of bromodomains. These protein modules are involved in the recognition of acetylated lysine side chains, a post‐translational modification frequently observed in histone tails. The molecular dynamics simulations have unmasked: (i) the large plasticity of the loops lining the acetyl‐lysine binding site (coupled to its self‐occlusion), and (ii) multiple binding modes of acetyl‐lysine. These simulation results suggest that recognition of histone tails by bromodomains is modulated by their intrinsic flexibility, and further corroborate the utility of molecular dynamics in understanding (macro)molecular recognition.
CCL27 Is Downregulated by Interferon Gamma via Epidermal Growth Factor Receptor in Normal Human Epidermal Keratinocytes
Authors: Karakawa Masaru , Komine Mayumi , Hanakawa Yasushi , Tsuda Hidetoshi , Sayama Koji , Tamaki Kunihiko , Ohtsuki Mamitaro
Published: April 2014

The cutaneous T cell‐attracting chemokine (CTACK)/CCL27 is indispensable in skin inflammation. CTACK/CCL27 is exclusively produced by epidermal keratinocytes to attract CCR10‐expressing T lymphocytes to the skin. We investigated the mechanism of CTACK/CCL27 production from normal human epidermal keratinocytes (NHEKs) by the proinflammatory cytokines TNFα and IFNγ. CTACK/CCL27 production was induced by TNFα via ERK, JNK, p38, and NFκB. The induction of CTACK/CCL27 by TNFα was suppressed by IFNγ via a pathway dependent on JAK, STAT1, and STAT3. Our results also demonstrated that IFNγ and TNFα induced the phosphorylation of EGFR and the following phosphorylation of ERK, which is partly responsible for the suppressive effect of IFNγ on TNFα‐induced production of CTACK/CCL27. Peri‐lesional skin of psoriasis demonstrates early inflammatory changes as we have previously reported. CTACK/CCL27 expression was diffuse in the peri‐lesional epidermis, while it was restricted to basal layer in lesional epidermis, suggesting that CTACK/CCL27 expression was induced in the early stage of psoriatic plaque formation, and IFNγ could participate in the suppression of CTACK/CCL27 expression in the lesional epidermis, reflecting the later stage of psoriatic plaque formation. Our study suggests that CTACK/CCL27 may have a pivotal role in the early stage of psoriasis plaque formation, but should be downregulated in the later stage to induce inflammation characteristic for chronic psoriasis plaques. J. Cell. Physiol. 229: 1935–1945, 2014. © 2014 Wiley Periodicals, Inc.