bluuebunny/crossref_metadata_2025 huggingface dataset:
A Concise and Highly Enantioselective Total Synthesis of (+)‐anti‐ and (−)‐syn‐Mefloquine Hydrochloride: Definitive Absolute Stereochemical Assignment of the Mefloquines
Authors: Rastelli Ettore J. , Coltart Don M.
Published: September 2015

A concise asymmetric (>99:1 e.r.) total synthesis of (+)‐anti‐ and (−)‐syn‐mefloquine hydrochloride from a common intermediate is described. The key asymmetric transformation is a Sharpless dihydroxylation of an olefin that is accessed in three steps from commercially available materials. The Sharpless‐derived diol is converted into either a trans or cis epoxide, and these are subsequently converted into (+)‐anti‐ and (−)‐syn‐mefloquine, respectively. The synthetic (+)‐anti‐ and (−)‐syn‐mefloquine samples were derivatized with (S)‐(+)‐mandelic acid tert‐butyldimethylsilyl ether, and a crystal structure of each derivative was obtained. These are the first X‐ray structures for mefloquine derivatives that were obtained by coupling to a known chiral, nonracemic compound, and provide definitive confirmation of the absolute stereochemistry of (+)‐anti‐ as well as (−)‐syn‐mefloquine.
A Concise and Highly Enantioselective Total Synthesis of (+)‐anti‐ and (−)‐syn‐Mefloquine Hydrochloride: Definitive Absolute Stereochemical Assignment of the Mefloquines
Authors: Rastelli Ettore J. , Coltart Don M.
Published: September 2015

A concise asymmetric (>99:1 e.r.) total synthesis of (+)‐anti‐ and (−)‐syn‐mefloquine hydrochloride from a common intermediate is described. The key asymmetric transformation is a Sharpless dihydroxylation of an olefin that is accessed in three steps from commercially available materials. The Sharpless‐derived diol is converted into either atransorcisepoxide, and these are subsequently converted into (+)‐anti‐ and (−)‐syn‐mefloquine, respectively. The synthetic (+)‐anti‐ and (−)‐syn‐mefloquine samples were derivatized with (S)‐(+)‐mandelic acidtert‐butyldimethylsilyl ether, and a crystal structure of each derivative was obtained. These are the first X‐ray structures for mefloquine derivatives that were obtained by coupling to a known chiral, nonracemic compound, and provide definitive confirmation of the absolute stereochemistry of (+)‐anti‐ as well as (−)‐syn‐mefloquine.
Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context
Authors: Sungur A. Özge , Schwarting Rainer K.W. , Wöhr Markus
Published: September 2015

Alterations in SHANK genes were repeatedly reported in autism spectrum disorder (ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent deficits in social communication/interaction across multiple contexts, with restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD are purely behaviorally defined and reliable biomarkers have still not been identified. The validity of mouse models for ASD therefore strongly relies on their behavioral phenotype. Here, we studied communication by means of isolation‐induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by comparing Shank1−/− null mutant, Shank1+/− heterozygous, and Shank1+/+ wildtype littermate controls. The first aim of the present study was to evaluate the effects of Shank1 deletions on developmental aspects of communication in order to see whether ASD‐related communication deficits are due to general impairment or delay in development. Second, we focused on social context effects on USV production. We show that Shank1−/− pups vocalized less and displayed a delay in the typical inverted U‐shaped developmental USV emission pattern with USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype difference on PND6. Moreover, testing under social conditions revealed even more prominently genotype‐dependent deficits regardless of the familiarity of the social context. As communication by definition serves a social function, introducing a social component to the typically nonsocial test environment could therefore help to reveal communication deficits in mouse models for ASD. Together, these results indicate that SHANK1 is involved in acoustic communication across species, with genetic alterations in SHANK1 resulting in social communication/interaction deficits. Autism Res 2016, 9: 696–709. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
A ROS‐Activatable Agent Elicits Homologous Recombination DNA Repair and Synergizes with Pathway Compounds
Authors: Thowfeik Fathima Shazna , AbdulSalam Safnas F. , Wunderlich Mark , Wyder Michael , Greis Kenneth D. , Kadekaro Ana L. , Mulloy James C. , Merino Edward J.
Published: September 2015

We designed ROS‐activated cytotoxic agents (RACs) that are active against AML cancer cells. In this study, the mechanism of action and synergistic effects against cells coexpressing the AML oncogenes MLL‐AF9 fusion and FLT3‐ITD were investigated. One RAC (RAC1) had an IC50 value of 1.8±0.3 μm, with ninefold greater selectivity for transformed cells compared to untransformed cells. Treatment induced DNA strand breaks, apoptosis, and cell cycle arrest. Proteomics and transcriptomics revealed enhanced expression of the pentose phosphate pathway, DNA repair, and pathways common to cell stress. Western blotting confirmed repair by homologous recombination. Importantly, RAC1 treatment was synergistic in combination with multiple pathway‐targeting therapies in AML cells but less so in untransformed cells. Together, these results demonstrate that RAC1 can selectively target poor prognosis AML and that it does so by creating DNA double‐strand breaks that require homologous recombination.
Pd@Al2O3‐Catalyzed Hydrogenation of Allylbenzene to Propylbenzene in Methanol and Aqueous Micellar Solutions
Authors: Arbelaez Oscar , Correa Luis , Parapat Riny Yolanda , Knemeyer Kristian , Bustamante Felipe , Villa Aída Luz , Schwarze Michael
Published: September 2015

The palladium on alumina (Pd@Al2O3)‐catalyzed hydrogenation of allylbenzene to propylbenzene was studied in methanol and aqueous micellar solutions of sodium dodecyl sulfate (SDS), decyltrimethylammonium bromide (DTAB), and t‐octylphenoxypolyethoxyethanol (TX‐100). Over Pd@Al2O3, propylbenzene was obtained via direct hydrogenation of allylbenzene and isomerization to β‐methylstyrene which was hydrogenated afterwards. In aqueous micellar solutions, the reaction was faster than in pure water, but slower than in methanol due to lower hydrogen solubility. In the H2O/SDS system, a higher activation energy was obtained than in methanol. For the investigated surfactants, the initial reaction rate in the micellar systems decreased in the order SDS > TX‐100 > DTAB.
Highly Specific Electrochemiluminescence Detection of Cancer Cells with a Closed Bipolar Electrode
Authors: Wu Mei‐Sheng , Liu Zhen , Xu Jing‐Juan , Chen Hong‐Yuan
Published: September 2015

An advanced biosensor based on a closed bipolar electrode (BPE)–electrochemiluminescence (ECL) strategy is proposed for cancer cell adhesion, specific recognition, and detection with dual biomarkers. The system consists of a two‐channel polydimethylsiloxane (PDMS) chip (sensing channel and reporting channel) connected through a U‐shaped indium tin oxide BPE at a glass surface. A sandwich‐type cancer cell detection model is developed at the cathode of the BPE with two recognition molecules, folic acid (FA) and an aptamer. On the basis of the high affinity between FA and the folate receptor that is overexpressed at a cancer cell membrane as well as the excellent conductivity of graphene–Au conjugates, this strategy could achieve the sensitive detection of HL‐60 cells, with a limit as low as 18 cells in 30 μL of cell suspension. Control experiments confirm that the sandwich assay specifically captures cancer cells and recognizes target cells.
Experimental and Computational Evidence of Highly Active Fe Impurity Sites on the Surface of Oxidized Au for the Electrocatalytic Oxidation of Water in Basic Media
Authors: Klaus Shannon , Trotochaud Lena , Cheng Mu‐Jeng , Head‐Gordon Martin , Bell Alexis T.
Published: September 2015

Addition of Fe to Ni‐ and Co‐based (oxy)hydroxides has been shown to enhance the activity of these materials for electrochemical oxygen evolution. Here we show that Fe cations bound to the surface of oxidized Au exhibit enhanced oxygen evolution reaction (OER) activity. We find that the OER activity increases with increasing surface concentration of Fe. Density functional theory analysis of the OER energetics reveals that oxygen evolution over Fe cations bound to a hydroxyl‐terminated oxidized Au (Fe–Au2O3) occurs at an overpotential ∼0.3 V lower than over hydroxylated Au2O3(0.82 V). This finding agrees well with experimental observations and is a consequence of the more optimal binding energetics of OER reaction intermediates at Fe cations bound to the surface of Au2O3. These findings suggest that the enhanced OER activity reported recently upon low‐potential cycling of Au may be due to surface Fe impurities rather than to “superactive” AuIIIsurfaquo species.
Self‐Assembly of Tetraphenylalanine Peptides
Authors: Mayans Enric , Ballano Gema , Casanovas Jordi , Díaz Angélica , Pérez‐Madrigal Maria M. , Estrany Francesc , Puiggalí Jordi , Cativiela Carlos , Alemán Carlos
Published: September 2015

Three different tetraphenylalanine (FFFF) based peptides that differ at the N‐ and C‐termini have been synthesized by using standard procedures to study their ability to form different nanoassemblies under a variety of conditions. The FFFF peptide assembles into nanotubes that show more structural imperfections at the surface than those formed by the diphenylalanine (FF) peptide under the same conditions. Periodic DFT calculations (M06L functional) were used to propose a model that consists of three FFFF molecules defining a ring through head‐to‐tail NH3+⋅⋅⋅−OOC interactions, which in turn stack to produce deformed channels with internal diameters between 12 and 16 Å. Depending on the experimental conditions used for the peptide incubation, N‐fluorenylmethoxycarbonyl (Fmoc) protected FFFF self‐assembles into a variety of polymorphs: ultra‐thin nanoplates, fibrils, and star‐like submicrometric aggregates. DFT calculations indicate that Fmoc‐FFFF prefers a parallel rather than an antiparallel β‐sheet assembly. Finally, coexisting multiple assemblies (up to three) were observed for Fmoc‐FFFF‐OBzl (OBzl = benzyl ester), which incorporates aromatic protecting groups at the two peptide terminals. This unusual and noticeable feature is attributed to the fact that the assemblies obtained by combining the Fmoc and OBzl groups contained in the peptide are isoenergetic.
Decanuclear Ln10 Wheels and Vertex‐Shared Spirocyclic Ln5 Cores: Synthesis, Structure, SMM Behavior, and MCE Properties
Authors: Das Sourav , Dey Atanu , Kundu Subrata , Biswas Sourav , Narayanan Ramakirushnan Suriya , Titos‐Padilla Silvia , Lorusso Giulia , Evangelisti Marco , Colacio Enrique , Chandrasekhar Vadapalli
Published: September 2015

The reaction of a Schiff base ligand (LH3) with lanthanide salts, pivalic acid and triethylamine in 1:1:1:3 and 4:5:8:20 stoichiometric ratios results in the formation of decanuclear Ln10 (Ln=Dy(1), Tb(2), and Gd (3)) and pentanuclear Ln5 complexes (Ln=Gd (4), Tb (5), and Dy (6)), respectively. The formation of Ln10 and Ln5 complexes are fully governed by the stoichiometry of the reagents used. Detailed magnetic studies on these complexes (1–6) have been carried out. Complex 1 shows a SMM behavior with an effective energy barrier for the reversal of the magnetization (Ueff)=16.12(8) K and relaxation time (τo)=3.3×10−5 s under 4000 Oe direct current (dc) field. Complex 6 shows the frequency dependent maxima in the out‐of‐phase signal under zero dc field, without achieving maxima above 2 K. Complexes 3 and 4 show a large magnetocaloric effect with the following characteristic values: −ΔSm=26.6 J kg−1 K−1 at T=2.2 K for 3 and −ΔSm=27.1 J kg−1 K−1 at T=2.4 K for 4, both for an applied field change of 7 T.
Transfer of Copper from an Amyloid to a Natural Copper‐Carrier Peptide with a Specific Mediating Ligand
Authors: Nguyen Michel , Bijani Christian , Martins Nathalie , Meunier Bernard , Robert Anne
Published: September 2015

The oxidative stress that arises from the catalytic reduction of dioxygen by CuII/I‐loaded amyloids is the major pathway for neuron death that occurs in Alzheimer’s disease. In this work, we show that bis‐8(aminoquinoline) ligands, copper(II) specific chelators, are able to catalytically extract CuII from Cu–Aβ1–16 and then completely release CuI in the presence of glutathione to provide a CuI–glutathione complex, a biological intermediate that is able to deliver copper to apo forms of copper–protein complexes. These data demonstrate that bis‐8(aminoquinolines) can perform the transfer of copper ions from the pathological Cu–amyloid complexes to regular copper–protein complexes. These copper‐specific ligands assist GSH to recycle CuI in an AD brain and consequently slow down oxidative damage that is due to copper dysregulation in Alzheimer’s disease. Under the same conditions, we have shown that the copper complex of PBT2, a mono(8‐hydroxyquinoline) previously used as a drug candidate, does not efficiently release copper in the presence of GSH. In addition, we report that GSH itself was unable to fully abstract copper ions from Cu–β‐amyloid complexes.
Synthesis of Phenylene Vinylene Macrocycles through Acyclic Diene Metathesis Macrocyclization and Their Aggregation Behavior
Authors: Zhang Chenxi , Yu Chao , Long Hai , Denman Ryan J. , Jin Yinghua , Zhang Wei
Published: September 2015

A series of phenylene vinylene macrocycles (PVMs) bearing substituents with various sizes and electronic properties have been synthesized through a one‐step acyclic diene metathesis macrocyclization approach and their aggregation behaviors have been investigated. In great contrast to the aggregation of the analogous phenylene ethynylene macrocycles, which aggregate only when substituted with electron‐withdrawing groups, these PVMs undergo exceptionally strong aggregation, regardless of the electron‐donating or ‐withdrawing characters of the substituents. The unusual aggregation behavior of the PVMs is further investigated with thermodynamic and computer modeling studies, which show a good agreement with the recently proposed direct through‐space interaction model, rather than the polar/π model. The high aggregation tendency of PVMs suggests the great potential of this novel class of shape‐persistent macrocycles in a variety of applications, such as ion channels, host–guest recognition, and catalysis.
Fluorescence Polarization Based Nucleic Acid Testing for Rapid and Cost‐Effective Diagnosis of Infectious Disease
Authors: Park Ki Soo , Charles Richelle C. , Ryan Edward T. , Weissleder Ralph , Lee Hakho
Published: September 2015

A new nucleic acid detection method was developed for a rapid and cost‐effective diagnosis of infectious disease. This approach relies on the three unique elements: 1) detection probes that regulate DNA polymerase activity in response to the complementary target DNA; 2) universal reporters conjugated with a single fluorophore; and 3) fluorescence polarization (FP) detection. As a proof‐of‐concept, the assay was used to detect and sub‐type Salmonella bacteria with sensitivities down to a single bacterium in less than three hours.
Cobalt(III)‐Catalyzed CH/NO Functionalizations: Isohypsic Access to Isoquinolines
Authors: Wang Hui , Koeller Julian , Liu Weiping , Ackermann Lutz
Published: September 2015

CH/NO functionalizations by cobalt(III) catalysis allowed the expedient synthesis of a broad range of isoquinolines. Thus, internal and challenging terminal alkynes proved to be viable substrates for an isohypsic annulation, which was shown to proceed by a facile CH cobaltation.
Synthesis, Structural Characterization, and Chiroptical Studies of Bidentate Salen‐Type Lanthanide (III) Complexes
Authors: Berardozzi Roberto , Pescitelli Gennaro , Di Pietro Sebastiano , Resta Claudio , Ballistreri Francesco P. , Pappalardo Andrea , Tomaselli Gaetano A. , Di Bari Lorenzo
Published: September 2015

The salen‐type ligand prepared with (R,R) diphenylethan‐1,2‐diamine and salicylaldehyde provides stable and inert complexes KLnL2 upon simple reaction with lanthanide halides or pseudohalides LnX3 (Ln = Tb3+‐Lu3+; X = Cl− or TfO−) of its potassium salt. All the complexes were completely characterized through nuclear magnetic resonance (NMR), electronic circular dichroism (ECD) in the UV and some (Er3+, Tm3+, Yb3+) also with Near‐IR ECD (NIR‐ECD) and luminescence (Tb3+, Tm3+). Careful analysis of the NMR shifts demonstrated that the complexes are isostructural in solution and afforded an accurate geometry. This was further confirmed by means of Density Functional Theory (DFT) optimization of the Lu3+ complex, and by comparing the ligand‐centered experimental and time‐dependent TD‐DFT computed UV‐ECD spectra. As final validation, we used the NIR‐ECD spectrum of the Yb3+ derivative calculated by means of Richardson's equations. The excellent match between calculated and experimental ECD spectra confirm the quality of the NMR structure.  Chirality 27:857–863, 2015. © 2015 Wiley Periodicals, Inc.
Covalent drug immobilization in poly(ester amide) nanoparticles for controlled release
Authors: Moustafa Amira , Abd Rabo Moustafa Mahmoud M. , Zilinskas Gregory J. , Gillies Elizabeth R.
Published: September 2015

The use of polymeric nanoparticles to encapsulate and deliver drug molecules is a promising approach for improving drug properties such as water dispersibility, pharmacokinetics, and selectivity for the in vivo target. Described here is the development of poly(ester amide) (PEA) nanoparticles prepared from PEAs with pendant functional groups that allow for covalent conjugation of the drugs in order to mitigate the undesirable burst release of drug, commonly observed for nanoparticle‐based drug delivery systems. Parameters including the surfactant and PEA concentration in an emulsification‐evaporation procedure were studied in order to determine conditions for preparing particles with diameters < 200 nm. A hydroxyl‐functionalized rhodamine derivative, as a model drug, was then conjugated to a PEA having pendant carboxylic acid groups to afford a PEA‐rhodamine conjugate with the dye covalently attached by ester linkages. The emulsification‐evaporation procedure was used to prepare nanoparticles from this conjugate and these particles were found to release the dye much more slowly and without a burst effect, in comparison with analogous nanoparticles having the rhodamine physically encapsulated. The same approach was applied to the anti‐cancer drug floxuridine and the resulting nanoparticles also afforded sustained drug release. This work suggests the promise of PEAs with pendant functional groups for providing nanoparticle‐based drug delivery vehicles with slow and sustained drug release.
Mechanochromic Fibers with Structural Color
Authors: Li Houpu , Sun Xuemei , Peng Huisheng
Published: September 2015

Responsive photonic crystals have been widely developed to realize tunable structural colors by manipulating the flow of light. Among them, mechanochromic photonic crystals attract increasing attention due to the easy operation, high safety and broad applications. Recently, mechanochromic photonic crystal fibers were proposed to satisfy the booming wearable smart textile market. In this Concept, the fundamental mechanism, fabrication, and recent progress on mechanochromic photonic crystals, especially in fiber shape, are summarized to represent a new direction in sensing and displaying.
How Sensitive is the Amide I Vibration of the Polypeptide Backbone to Electric Fields?
Authors: Oh Kwang‐Im , Fiorin Giacomo , Gai Feng
Published: September 2015

Site‐selective isotopic labeling of amide carbonyls offers a nonperturbative means to introduce a localized infrared probe into proteins. Although this strategy has been widely used to investigate various biological questions, the dependence of the underlying amide I vibrational frequency on electric fields (or Stark tuning rate) has not been fully determined, which prevents it from being used in a quantitative manner in certain applications. Herein, through the use of experiments and molecular dynamics simulations, the Stark tuning rate of the amide I vibration of an isotopically labeled backbone carbonyl in a transmembrane α‐helix is determined to be approximately 1.4 cm−1/(MV/cm). This result provides a quantitative basis for using this vibrational model to assess local electric fields in proteins, among other applications. For instance, by using this value, we are able to show that the backbone region of a dipeptide has a surprisingly low dielectric constant.
Bandgap‐ and Radial‐Position‐Dependent Mn‐Doped Zn–Cu–In–S/ZnS Core/Shell Nanocrystals
Authors: Peng Lucheng , Huang Keke , Zhang Zhuolei , Zhang Ying , Shi Zhan , Xie Renguo , Yang Wensheng
Published: September 2015

This paper presents a mechanistic study on the doping of Zn–Cu–In–S/ZnS core/shell quantum dots (QDs) with Mn by changing the Zn–Cu–In–S QD bandgap and dopant position inside the samples (Zn–Cu–In–S core and ZnS shell). Results show that for the Mn:Zn–Cu–In–S/ZnS system, a Mn‐doped emission can be obtained when the bandgap value of the QDs is larger than the energy of Mn‐doped emission. Conversely, a bandgap emission is only observed for the doped system when the bandgap value of QDs is smaller than the energy gap of the Mn‐doped emission. In the Zn–Cu–In–S/Mn:ZnS systems, doped QDs show dual emissions, consisting of bandgap and Mn dopant emissions, instead of one emission band when the value of the host bandgap is larger than the energy of the Mn‐doped emission. These findings indicate that the emission from Mn‐doped Zn–Cu–In–S/ZnS core/shell QDs depends on the bandgap of the QDs and the dopant position inside the core/shell material. The critical bandgap of the host materials is estimated to have the same value as the energy of the Mn d–d transition. Subsequently, the mechanism of photoluminescence properties of the Mn:Zn–Cu–In–S/ZnS and Zn–Cu–In–S/Mn:ZnS core/shell QD systems is proposed. Control experiments are then carried out by preparing Mn‐doped Zn(Cu)–In–S QDs with various bandgaps, and the results confirm the reliability of the suggested mechanism. Therefore, the proposed mechanism can aid the design and synthesis of novel host materials in fabricating doped QDs.
DNA Microenvironment Monitored by Controlling Redox Blinking
Authors: Kawai Kiyohiko , Higashiguchi Kenji , Maruyama Atsushi , Majima Tetsuro
Published: September 2015

The rate of a bimolecular reaction between a fluorophore and a freely diffusing molecule in the solvent depends on the accessibility of the fluorophore for collision with the molecule. We previously reported that the observation of blinking, caused by the formation of R6G in the excited triplet state (3R6G*) and its quenching reaction with O2, allowed us to monitor the DNA conformational changes between a duplex and a hairpin. However, the small molecular size of O2 hampered sensitive monitoring of the microenvironment changes around R6G. In this study, we control redox blinking by adding a reductant ascorbic acid 2‐phosphate (VcP), which converts 3R6G* into the radical anion form R6G.−, and by adding a bulky oxidant FeDTPA. The bimolecular electron‐transfer rate between R6G.− and bulky FeDTPA was more strongly affected by microenvironment changes around R6G, compared with that between 3R6G* and the smaller O2. This allowed us to monitor subtle DNA conformational changes caused by a single different nucleotide.
Conductometric study of calcium carbonate prenucleation stage: underlining the role of CaCO3o ion pairs
Authors: Hamdi Raghda , Tlili Mohamed Mouldi
Published: September 2015

Calcium carbonate crystallization process, especially the prenucleation stage, has increasingly been the subject of several works. In the present work, a simple method based on electrical conductivity modeling applied to the FCP (Fast Controlled Precipitation) method data is used to highlight the role of CaCO3o ion pairs on calcium carbonate prenucleation stage. A good agreement was obtained between the resistivity vs pH curves estimated by the McCleskey model equation and obtained experimentally in a FCP test. Results showed that the nucleation process begins with the formation of CaCO3o ion pairs as pre‐nuclei as soon as the calcite‐equilibrium pH is reached. Additionally CaCO3o content increases with pH to form aggregates, which depend on the saturation state of the solution. Basing on our thermodynamic data, these aggregates do not form amorphous calcium carbonate ACC as an intermediate phase. They lead to the formation of stable calcium carbonate nuclei which will further evolve to crystallize. Furthermore we demonstrate that in addition to their inhibitory effect on the Ca2+ and CO32− association to form ion pairs, the two scale inhibitors sodium triphosphate (STP) and sodium polyacrylate (RPI) reduce ion pairs aggregation rate.
Retracted: High‐speed FSK modulator using switched‐capacitor resonators
Authors: Salehi Mohsen
Published: September 2015

The above article, published online on 30 September 2015 in Wiley Online Library (http://www.onlinelibrary.wiley.com), has been retracted by agreement between the journal Editor in Chief, Ángel Rodríguez‐Vázquez, and John Wiley & Sons, Ltd. Following an investigation by the institution of the author, the retraction has been agreed because a co‐author was not informed of the submission and did not provide consent for it to proceed. In addition, the co‐author was not acknowledged in the manuscript itself. The article is to be retracted at the request of the co‐author.

Reference

Salehi M. (2015) . Int. J. Circ. Theor. Appl., doi:10.1002/cta.2157.
Two base station location techniques with adjusted measurements in circular scattering environments
Authors: Wu Shixun , Xu Dengyuan , Tan Jin , Xu Kai , Wang Honggang
Published: September 2015

In circular scattering environments, novel location techniques with only two base stations (BSs) are proposed in this paper. The proposed techniques estimate the true or line‐of‐sight ranges and angle based on non‐line‐of‐sight range and angle measurements. Three new variables are introduced when range measurements and angle measurement are available from two BSs and the serving BS, respectively. Bounds and relationships between the three variables are extracted from the geometry of the cell layout with the unknown and known scattering radius conditions, respectively. Our aim is to obtain the estimation of three new variables and then the hybrid line of position technique with the adjusted ranges, and angle is utilized to obtain the position estimation of a mobile station. In order to obtain the estimation of three new variables, a new nonlinear objective function is built to form the constrained nonlinear optimization and solved by the existing optimization algorithms. However, because of the nonconvex objective function, the optimization algorithm may converge to the local optimum and lead to bad performance. Thus, a heuristic search algorithm is proposed by averaging all the potential point. Simulation results show that the proposed techniques outperform conventional hybrid techniques. Copyright © 2015 John Wiley & Sons, Ltd.
Which heart failure patients profit from natriuretic peptide guided therapy? A meta‐analysis from individual patient data of randomized trials
Authors: Brunner‐La Rocca Hans‐Peter , Eurlings Luc , Richards A. Mark , Januzzi James L. , Pfisterer Matthias E. , Dahlström Ulf , Pinto Yigal M. , Karlström Patric , Erntell Hans , Berger Rudolf , Persson Hans , O'Connor Christopher M. , Moertl Deddo , Gaggin Hanna K. , Frampton Christopher M. , Nicholls M. Gary , Troughton Richard W.
Published: September 2015

Aims

Previous analyses suggest that heart failure (HF) therapy guided by (N‐terminal pro‐)brain natriuretic peptide (NT‐proBNP) might be dependent on left ventricular ejection fraction, age and co‐morbidities, but the reasons remain unclear.

Methods and results

To determine interactions between (NT‐pro)BNP‐guided therapy and HF with reduced [ejection fraction (EF) ≤45%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n = 301] and co‐morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT‐proBNP guidance trials were analysed using Cox‐regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT‐pro)BNP‐guided compared with symptom‐guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62–0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67–0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76–1.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67–1.53, P = 0.97; interactions P < 0.02). Age (74 ± 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co‐morbidities. In HFpEF, renal failure provided strongest interaction (P < 0.01; increased risk of (NT‐pro)BNP‐guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co‐morbidities provided strongest interaction (P < 0.01; (NT‐pro)BNP‐guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT‐pro)BNP‐guided therapy was harmful in HFpEF patients without hypertension (P = 0.02).

Conclusion

The benefits of therapy guided by (NT‐pro)BNP were present in HFrEF only. Co‐morbidities seem to influence the response to (NT‐pro)BNP‐guided therapy and may explain the lower efficacy of this approach in elderly patients.
Structural Insights into the Binding of Sugar Receptors (Lectins) to a Synthetic Tricyclic Tn Mimetic and Its Glycopeptide Version
Authors: Ardá Ana , Bosco Rosa , Sastre Javier , Cañada F. Javier , André Sabine , Gabius Hans‐Joachim , Richichi Barbara , Jiménez‐Barbero Jesus , Nativi Cristina
Published: September 2015

Cycloadduct 1 is a conformationally constrained mimetic of the tumor‐associated Tn antigen. It maintains the 4C1 conformation and the α‐O‐glycosidic linkage of the natural epitopes. Due to its tricyclic structure, the anomeric linkage is constrained and its conformation “frozen”. Using saturation transfer difference NMR spectroscopy experiments, epitope mapping for binding by three lectins [i.e., from Erythrina cristagalli (ECL), human macrophages (MGL), and from Helix pomatia (HPA)] was carried out. Striking differences in the epitope viewed from the ligand's perspective were revealed by this comparison. Evidently, the structural change around the C‐2 position has a major impact, if the contact pattern to the ligand is not mostly restricted to galacto configuration with the axial hydroxyl group at C‐4, in combination with C‐3/C‐6. These measurements thus provide insights into actual contacts, which help predict applicability as an inhibitor for distinct lectins, and as an elicitor of specific antibodies.
Deciphering mechanisms of malathion toxicity under pulse exposure of the freshwater cladoceran Daphnia magna
Authors: Trac Lam Ngoc , Andersen Ole , Palmqvist Annemette
Published: September 2015

The organophosphate pesticide (OP) malathion is highly toxic to freshwater invertebrates, including the cladoceran Daphnia magna, a widely used test organism in ecotoxicology. To assess whether toxic effects of malathion are driven primarily by exposure concentration or exposure duration, D. magna was pulse exposed to equivalent integrated doses (duration × concentration): 3 h × 16 μg/L, 24 h × 2 μg/L, and 48 h × 1 μg/L. After recovery periods of 3 h, 24 h, and 48 h, the toxicity of malathion on different biological levels in D. magna was examined by analyzing the following endpoints: survival and immobilization; enzyme activities of acetylcholinesterase (AChE), carboxylesterase (CbE), and glutathione S-transferase (GST); and AChE gene expression. The results showed no difference in survival among equivalent integrated doses. Adverse sublethal effects were driven by exposure concentration rather than pulse duration. Specifically, short pulse exposure to a high concentration of malathion resulted in more immobilized daphnids, lower AChE and CbE activities, and a higher transcript level of AChE gene compared with long pulse exposure to low concentration. The expression of the AChE gene was up-regulated, indicating a compensatory mechanism to cope with enzyme inhibition. The study shows the need for obtaining a better understanding of the processes underlying toxicity under realistic exposure scenarios, so this can be taken into account in environmental risk assessment of pesticides. Environ Toxicol Chem 2016;35:394–404. © 2015 SETAC
Pesticide determination in rose concrete and rose absolute using dispersive‐solid phase extraction followed by gas chromatography‐tandem mass spectrometry
Authors: Tascone Oriane , Roy Céline , Meierhenrich Uwe J.
Published: September 2015

The rose species Rosa damascena and Rosa centifolia are cultivated for their use as perfume raw materials. The solvent extract of rose petals provides the concrete that is further transformed into the absolute. Both, concrete and absolute contain a variety of organic molecules. As a result of the lack of an adequate analytical procedure and the complexity of the matrices, the accurate quantification of pesticides in concrete and absolute remains challenging. Here we describe the first analytical method to quantify 57 pesticide residues in rose concrete and 56 pesticide residues in rose absolute. The method uses a multistep dispersive‐solid phase extraction (d‐SPE) cleanup followed by injection in a gas chromatography‐tandem mass spectrometer. Sample preparation includes the extraction of analytes from the matrix using acetonitrile and a mixture of salts and a double clean‐up step using sorbents in the form of primary and secondary amines (PSA), magnesium sulphate, C18 and graphitized carbon black (GCB). Two fortification levels, 0.025 to 0.15 and 0.5 mg/kg, were assessed. For 56 pesticides, the obtained recoveries were within the range of 70% to 120 % with a relative standard deviation (RSD) lower than 20% at each spiked level. The validation parameters proved that the developed method can be used for the quantification of 57 pesticide residues in rose concrete and 56 pesticide residues in rose absolute with a limit of quantification (LOQ) ranging from 0.025 to 0.1 mg/kg in concrete and from 0.05 to 0.15 mg/kg in absolute, depending on the active substance. Copyright © 2015 John Wiley & Sons, Ltd.
Pain grade and sleep disturbance in older adults: evaluation the role of pain, and stress for depressed and non‐depressed individuals
Authors: Eslami Vahid , Zimmerman Molly E. , Grewal Trishdeep , Katz Mindy , Lipton Richard B.
Published: September 2015

Objective

The aim of this paper was to assess the relationship between pain and sleep in older adults taking depression, stress, and medical comorbidities into account.

Methods

A cross‐sectional analysis was performed using Einstein Aging Study, a community‐based cohort study of adults aged 70 years and older. Ratings of pain intensity and interference from the Medical Outcomes Study (MOS) Short‐Form 36 were used to assign individuals to low‐pain versus high‐pain severity. Sleep disturbance was assessed using the nine‐item sleep problems index from the Medical Outcomes Study Sleep Scale. Other measures included the Geriatric Depression Scale and Perceived Stress Scale (PSS). Linear regression models were used to assess the association between pain grade and sleep disturbance adjusted for demographics, PSS, Geriatric Depression Scale, and other comorbidities.

Results

Five hundred sixty‐two eligible participants with a mean age of 78.22 years (standard deviation = 5.43) were included; 64% were women. Pain grade [β = 5.40, 95% confidence interval (CI) 2.56–8.21, p < 0.001] was associated with sleep disturbance after adjusting for demographic variables. In models including pain grade (β = 3.08, 95% CI 0.32–5.85, p = 0.03) and PSS (β = 0.57, 95% CI 0.39–0.75, p < 0.001), both were associated with sleep disturbance, although the PSS attenuated the relationship between pain and sleep by 34%. Depression, when added to previous model, was also associated with sleep (β = 2.17, 95% CI 1.48–2.85, p < 0.001) and attenuated the relationship between pain (β = 2.41, 95% CI −0.25 to 5.08, p = 0.07) and sleep by 22%. Stratified for depression, we found that pain, stress, and other medical comorbidities were significantly associated with sleep disturbance in non‐depressed individuals but not individuals with depression.

Conclusions

Pain, stress, and medical comorbidities are associated with sleep disturbance, especially in non‐depressed older adults.
Suicide attempts and completions in Veterans Affairs nursing home care units and long‐term care facilities: a review of root‐cause analysis reports
Authors: Mills Peter D. , Gallimore Bradley I. , Watts B. Vince , Hemphill Robin R.
Published: September 2015

Objective

Suicide was the 10th leading cause of death for Americans in 2010. The suicide rate is highest among men who are aged 75 and older. The prevalence of suicidal behavior in nursing homes and long‐term care (LTC) facilities was estimated to be 1%. This study describes the systemic vulnerabilities found after suicidal behavior in LTC facilities as well as steps to decrease or mitigate the risk.

Method

This is a retrospective review of root‐cause analysis (RCA) reports of suicide attempts and completions between 1 January 2000 and 31 December 2013 in the Veterans Health Administration LTC and nursing home care units. The RCA reports of suicide attempts and completions were coded for patient demographics, method of attempt or completion, root causes, and actions developed to address the root cause.

Results

Thirty‐five RCA reports were identified. The average age was 65 years, 11 had a previous suicide attempt, and the primary mental health diagnoses were depression, posttraumatic stress disorder, and schizophrenia. The primary methods of self‐harm were cutting with a sharp object, overdose, and strangulation.

Conclusions

It is recommended that all staff members are aware of the signs and risk factors for depression and suicide in this population and should systematically assess and treat mental disorders. In addition, LTC facilities should have a standard protocol for evaluating the environment for suicide hazards and use interdisciplinary teams to promote good communication about risk factors identified among patients. Finally, staff should go beyond staff education and policy to make clinical changes at the bedside. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Velocities, celerities and the basin of attraction in catchment response
Authors: Beven Keith , Davies Jess
Published: September 2015

Catchment systems are interestingly nonlinear, but their dynamics are constrained from being unduly chaotic by mass and energy balance requirements. There have been no attempts in hydrology that we know of that have tried to map both the flow and transport dynamics of a catchment in any form of phase space. In part, this is because of the high dimensionality of the space–time patterns of response; in part because there is sufficient uncertainty about the input and output fluxes estimated by measurement that this might be expected to obscure any attractor‐like behaviour. In this study we explore the basin of the catchment attractor for the Multiple Interacting Pathway (MIPs) model that in previous papers has been shown to give good results for the small Gårdsjön catchment in Sweden. MIPs is based on particle tracking techniques and gives results for both the flow responses and for the travel and residence time responses of water in the catchment. Here it is used to provide consistent values of fluxes, total storage, travel time distributions and residence time distributions for a long simulation period. The nature of those responses in storage and input dimensions is then investigated. The results suggest that the range of behaviours is hysteretic in interesting ways and constrained by the forcing inputs, with space filling of trajectories in the basin of attraction as should be expected of a forced dissipative system. The range of behaviours exhibited defines a space that the responses of any simpler emulator model will need to span. © 2015 The Authors Hydrological Processes Published by John Wiley & Sons Ltd.
Changes in canopy transpiration of Japanese cypress and Japanese cedar plantations because of selective thinning
Authors: Tateishi Makiko , Xiang Yang , Saito Takami , Otsuki Kyoichi , Kasahara Tamao
Published: September 2015

Canopy transpiration (Estand) is a main component of forest water cycle, and forest management including thinning affects canopy transpiration Estand, yet few studies have examined the changes in Estand. In this study, we investigated the changes in Estand after the thinning of Chamaecyparis obtusa and Cryptomeria japonica stands by 50% of their stems. The Estand was estimated using sap flow measurements by Granier‐type thermal dissipation probes. The mean stand sap flow density (JS) after thinning was as high as that before thinning in both plots. Under the same conditions of microclimate, Estand after thinning decreased by 44.0 and 21.2% for the Ch. obtusa plot and the Cr. japonica plot, respectively. The thinning reduced the sapwood area by 44.5% in the Ch. obtusa plot and 34.2% in the Cr. japonica plot. The decreases in Estand were similar to the decline in sapwood area, which indicates that the primary cause of the changes in Estand was the reduction of sapwood area. The reference canopy conductance (Gcref) after thinning was 52.7% and 75.3% lower for Ch. obtusa and Cr. japonica, respectively, whereas stomatal sensitivity to the vapour pressure deficit was similar in both periods. Thus, the changes in canopy conductance after thinning were associated with changes in Gcref, resulting in a decrease of Estand. Copyright © 2015 John Wiley & Sons, Ltd.
Dysregulation of host cellular genes targeted by human papillomavirus (HPV) integration contributes to HPV‐related cervical carcinogenesis
Authors: Zhang Ruiyang , Shen Congle , Zhao Lijun , Wang Jianliu , McCrae Malcolm , Chen Xiangmei , Lu Fengmin
Published: September 2015

Integration of human papillomavirus (HPV) viral DNA into the human genome has been postulated as an important etiological event during cervical carcinogenesis. Several recent reports suggested a possible role for such integration‐targeted cellular genes (ITGs) in cervical carcinogenesis. Therefore, a comprehensive analysis of HPV integration events was undertaken using data collected from 14 publications, with 499 integration loci on human chromosomes included. It revealed that HPV DNA preferred to integrate into intragenic regions and gene‐dense regions of human chromosomes. Intriguingly, the host cellular genes nearby the integration sites were found to be more transcriptionally active compared with control. Furthermore, analysis of the integration sites in the human genome revealed that there were several integration hotspots although all chromosomes were represented. The ITGs identified were found to be enriched in tumor‐related terms and pathways using gene ontology and KEGG analysis. In line with this, three of six ITGs tested were found aberrantly expressed in cervical cancer tissues. Among them, it was demonstrated for the first time that MPPED2 could induce HeLa cell and SiHa cell G1/S transition block and cell proliferation retardation. Moreover, “knocking out” the integrated HPV fragment in HeLa cell line decreased expression of MYC located ∼500 kb downstream of the integration site, which provided the first experimental evidence supporting the hypothesis that integrated HPV fragment influence MYC expression via long distance chromatin interaction. Overall, the results of this comprehensive analysis implicated that dysregulation of ITGs caused by viral integration as possibly having an etiological involvement in cervical carcinogenesis.
Alterations in cellular metabolome after pharmacological inhibition of Notch in glioblastoma cells
Authors: Kahlert Ulf D. , Cheng Menglin , Koch Katharina , Marchionni Luigi , Fan Xing , Raabe Eric H. , Maciaczyk Jarek , Glunde Kristine , Eberhart Charles G.
Published: September 2015

Notch signaling can promote tumorigenesis in the nervous system and plays important roles in stem‐like cancer cells. However, little is known about how Notch inhibition might alter tumor metabolism, particularly in lesions arising in the brain. The gamma‐secretase inhibitor MRK003 was used to treat glioblastoma neurospheres, and they were subdivided into sensitive and insensitive groups in terms of canonical Notch target response. Global metabolomes were then examined using proton magnetic resonance spectroscopy, and changes in intracellular concentration of various metabolites identified which correlate with Notch inhibition. Reductions in glutamate were verified by oxidation‐based colorimetric assays. Interestingly, the alkylating chemotherapeutic agent temozolomide, the mTOR‐inhibitor MLN0128, and the WNT inhibitor LGK974 did not reduce glutamate levels, suggesting that changes to this metabolite might reflect specific downstream effects of Notch blockade in gliomas rather than general sequelae of tumor growth inhibition. Global and targeted expression analyses revealed that multiple genes important in glutamate homeostasis, including glutaminase, are dysregulated after Notch inhibition. Treatment with an allosteric inhibitor of glutaminase, compound 968, could slow glioblastoma growth, and Notch inhibition may act at least in part by regulating glutaminase and glutamate.
Using Remote Sensing to Estimate Evapotranspiration of Irrigated Crops Under Flood and Sprinkler Irrigation Systems
Authors: Eldeiry Ahmed A. , Waskom Reagan M. , Elhaddad Aymn
Published: September 2015

The objectives of this study are to: (i) estimate the actual evapotranspiration (ETa) of the different irrigated crops in the South Platte River Basin, Colorado, USA; (ii) compare the consumption use for the irrigated areas for 2001 and 2010; (iii) investigate the impact of irrigation system (flood/sprinkler) on the estimated ETa. The ReSET model, a surface energy balance remote sensing based model, is used in this study to estimate the ETa of the South Platte River Basin irrigated crops for 2001 and 2010. Landsat 5/7 satellite images, weather data, shape files of irrigated crops, and a digital elevation model (DEM) were acquired and processed for the study area. The results of this study show that the estimated ETa using the ReSET model showed a reduction of 7.1% from 2.51 × 109 m3 in 2001 to 2.33 × 109 m3 in 2010, mainly due to the reduction of the irrigated area from 2001 to 2010 by 6.6%. The estimated total ETa of crops irrigated with flood irrigation systems decreased from 66.1 to 54.6%, while the estimated total ETa of crops irrigated with sprinkler systems increased from 33.9 to 45.4%. For 2001, the average seasonal ETa of all crops for flood irrigation and sprinkler irrigation, respectively, were 665 and 712 mm, with a 7% greater ETa for sprinkler systems. The ReSET model ETa estimates have been validated in a previous study of lysimeter measurements. However, in this study and due to the unavailability of a lysimeter, the model ETa estimates were verified with the reference evapotranspiration (ETr) of the weather stations in the study area. The results of the t‐test shows a p‐value = 0.124, greater than 0.05, which indicates that the means of the ReSET ETa estimates and the ETr are not significantly different. Additionally, the results of the F‐test shows a p‐value = 0.674, greater than 0.05, which indicates that the two variances of the ReSET ETa estimates and the ETr are homogeneous. Copyright © 2015 John Wiley & Sons, Ltd.