bluuebunny/crossref_metadata_2025 huggingface dataset:
System identification techniques based on support vector machines without bias term
Authors: Vogt Michael
Published: June 2013

The intention of this article is to utilize support vector machines (SVMs) as process models, which are the basis for most controller designs as well as simulation and monitoring tasks. SVMs are data‐driven models comparable with regularization networks, which merge elements from robust statistics, statistical learning, and kernel theory. The presentation is focused on the ‘no‐bias‐term’ variant, accounts for several peculiarities specific to SVM regression and derives an active‐set algorithm to solve the resulting large‐scale quadratic programming problem. For linear systems, SVMs are combined with multi‐stage methods for estimating output error and ARMAX models. Finally, two real‐world processes serve as test cases to evaluate the SVMs’ properties as nonlinear dynamic models. Copyright © 2013 John Wiley & Sons, Ltd.
Direct Evidence of Cation Disorder in Thermoelectric Lead Chalcogenides PbTe and PbS
Authors: Kastbjerg Sofie , Bindzus Niels , Søndergaard Martin , Johnsen Simon , Lock Nina , Christensen Mogens , Takata Masaki , Spackman Mark A. , Brummerstedt Iversen Bo
Published: June 2013

The extraordinary thermoelectric properties of lead chalcogenides have attracted huge interest in part due to their unexpected low thermal conductivity. Here, it is shown that anharmonicity and large cation disorder are present in both PbTe and PbS, based on elaborate charge density visualization using synchrotron powder X‐ray diffraction (SPXRD) data analyzed with the maximum entropy method (MEM). In both systems, the cation disorder increases with increasing temperature, whereas the Te/S anions appear to be centered on the expected lattice positions. Even at the lowest temperatures of 105 K, the lead ion is on average displaced by ≈0.2 Å from the rock‐salt lattice position, creating a strong phonon scattering mechanism. These findings provide a clue to understanding the excellent thermoelectric performance of crystals with atomic disorder. The SPXRD–MEM approach can be applied in general opening up for widespread characterization of subtle structural features in crystals with unusual properties.
Towards an Improved anti‐HIV Activity of NRTI via Metal–Organic Frameworks Nanoparticles
Authors: Agostoni Valentina , Chalati Tamim , Horcajada Patricia , Willaime Hervé , Anand Resmi , Semiramoth Nicolas , Baati Tarek , Hall Shaun , Maurin Guillaume , Chacun Hélène , Bouchemal Kawthar , Martineau Charlotte , Taulelle Francis , Couvreur Patrick , Rogez‐Kreuz Christine , Clayette Pascal , Monti Sandra , Serre Christian , Gref Ruxandra
Published: June 2013

Nanoscale mesoporous iron carboxylates metal–organic frameworks (nanoMOFs) have recently emerged as promising platforms for drug delivery, showing biodegradability, biocompatibility and important loading capability of challenging highly water‐soluble drugs such as azidothymidine tryphosphate (AZT‐TP). In this study, nanoMOFs made of iron trimesate (MIL‐100) were able to act as efficient molecular sponges, quickly adsorbing up to 24 wt% AZT‐TP with entrapment efficiencies close to 100%, without perturbation of the supramolecular crystalline organization. These data are in agreement with molecular modelling predictions, indicating maximal loadings of 33 wt% and preferential location of the drug in the large cages. Spectrophotometry, isothermal titration calorimetry, and solid state NMR investigations enable to gain insight on the mechanism of interaction of AZT and AZT‐TP with the nanoMOFs, pointing out the crucial role of phosphates strongly coordinating with the unsaturated iron(III) sites. Finally, contrarily to the free AZT‐TP, the loaded nanoparticles efficiently penetrate and release their cargo of active triphosphorylated AZT inside major HIV target cells, efficiently protecting against HIV infection.
Spin clocks: Probing fundamental symmetries in nature
Authors: Heil Werner , Gemmel Claudia , Karpuk Sergei , Sobolev Yuri , Tullney Kathlynne , Allmendinger Fabian , Schmidt Ulrich , Burghoff Martin , Kilian Wolfgang , Knappe‐Grüneberg Silvia , Schnabel Allard , Seifert Frank , Trahms Lutz
Published: June 2013

The detection of the free precession of co‐located 3He/129Xe nuclear spins (clock comparison) is used as ultra‐sensitive probe for non‐magnetic spin interactions, since the magnetic dipole interaction (Zeeman‐term) drops out in the weighted frequency difference, i.e., Δω = ωHe‐ γHe/γXe·ωXe of the respective Larmor frequencies. Recent results are reported on searches for (i) short‐range P‐ and T‐violating interactions between nucleons, and (ii) Lorentz violating signatures by monitoring the Larmor frequencies as the laboratory reference frame rotates with respect to distant stars (sidereal modulation). Finally, a new experimental initiative to search for an electric dipole moment of 129Xe (CP‐violation) is discussed, which strongly benefits from the long spin‐coherence times obtained, reaching > 100 h and > 8 h in case of 3He and 129Xe, respectively.
Transmetallierung in der Suzuki‐Miyaura‐Kupplung: Gabelung des Reaktionsverlaufs
Authors: Lennox Alastair J. J. , Lloyd‐Jones Guy C.
Published: June 2013

Die Suzuki‐Miyaura‐Kupplung ist eine der wenigen übergangsmetallkatalysierten Reaktionen zur C‐C‐Bindungsbildung, die eine weite Verbreitung in der Forschungs‐ und industriellen Chemie gefunden haben. Obwohl die Kupplung über die allgemeine dreistufige Abfolge von oxidativer Addition, Transmetallierung und reduktiver Eliminierung abläuft, gibt es eine Reihe von Merkmalen, in denen sich das Suzuki‐Miyaura‐Verfahren von anderen übergangsmetallkatalysierten Kreuzkupplungen unterscheidet. Dies betrifft vor allem die Aktivierung des Borreagens für die Transmetallierung, die über zwei unterschiedliche Wege verlaufen kann. In diesem Kurzaufsatz fassen wir die Ergebnisse bezüglich dieser beiden charakteristischen Mechanismen zusammen und beschreiben das Potenzial, das ein solcher mechanistischer Einblick für die Gestaltung der Reaktionsbedingungen hat.
Ethylene vinyl acetate/nanoclay‐based pigment composites: Morphology, rheology, and mechanical, thermal, and colorimetric properties
Authors: Marchante Veronica , Benavente Veronica , Marcilla Antonio , Martínez‐Verdú Francisco Miguel , Beltrán Maria Isabel
Published: June 2013

In this study, a new type of nanopigment, obtained from a nanoclay (NC) and a dye, was synthesized in the laboratory, and these nanopigments were used to color an ethylene vinyl acetate (EVA) copolymer. Several of these nanoclay‐based pigments (NCPs) were obtained through variations in the cation exchange capacity (CEC) percentage of the NC exchanged with the dye and also including an ammonium salt. Composites of EVA and different amounts of the as‐synthesized nanopigments were prepared in a melt‐intercalation process. Then, the morphological, mechanical, thermal, rheological, and colorimetric properties of the samples were assessed. The EVA/NCP composites developed much better color properties than the samples containing only the dye, especially when both the dye and the ammonium salt were exchanged with NC. Their other properties were similar to those of more conventional EVA/NC composites. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 2987–2994, 2013
Negligible recovery in Chagos holothurians (sea cucumbers)
Authors: Price A.R.G. , Evans L.E. , Rowlands N. , Hawkins J.P.
Published: June 2013

Extensive sampling in 2006 quantified variations in shallow‐water holothurian abundance across the Chagos Archipelago, British Indian Ocean Territory, and revealed negative effects of illegal poaching. Median abundance in Diego Garcia, where exploitation is absent, was significantly higher than in three exploited atolls.

Repeat surveys undertaken along 64 comparable 100 m × 2 m transects during February 2010 revealed highest median abundance in the Great Chagos Bank, and also significant decline in abundance at Diego Garcia since 2006.

Comparison of surveys in 2010 and 2006 with an investigation in 2002 reveals an overall decline in populations of Stichopus chloronotus, Holothuria atra and Holothuria nobilis over 8 years in the exploited atolls of Salomon and Peros Banhos, despite evidence of reduced fishing since 2005/2006 in these and other exploited atolls.

A complete census of a large transect, 19 km × 4 m, encircling Salomon atoll, revealed lower total holothurian abundance in 2010 (1661 individuals) than 2006 (2142 individuals).

Although information on fishing pressure at different northern islands is not available for 2010, the significant decline in holothurian abundance between 2006 and 2010 observed in Diego Garcia, where poaching is absent, suggests that factors besides fishing also drive populations in Chagos.

The designation in April 2010 of Chagos as the world's largest marine protected area may help accelerate recovery of holothurian populations, as has occurred in marine reserves in the Seychelles. However, this requires increased monitoring, control and surveillance capacity.

Copyright © 2013 John Wiley & Sons, Ltd.
Brief Report: Magnetic Resonance Imaging Assessment of Axial Psoriatic Arthritis: Extent of Disease Relates to HLA–B27
Authors: Castillo‐Gallego Concepción , Aydin Sibel Z. , Emery Paul , McGonagle Dennis G. , Marzo‐Ortega Helena
Published: June 2013

Objective

To determine the prevalence, on magnetic resonance imaging (MRI), of bone marrow edema lesions in symptomatic axial psoriatic arthritis (PsA), and to compare this prevalence with that in nonradiographic axial spondyloarthritis (SpA) and ankylosing spondylitis (AS) and its relationship to HLA–B27 status.

Methods

We performed a cross‐sectional audit of MRI scans of lumbar spine (L‐spine) and sacroiliac (SI) joints. Using the semiquantitative Leeds Scoring System in which bone marrow edema is graded from 0 to 3 according to severity of the lesions, MRI scans were scored independently by 2 expert readers who were blinded to the clinical characteristics of the patients. Concordant data from the 2 readers were used to report on definite lesions.

Results

MRIs from 76 patients with comparable age ranges were categorized into 3 groups: those from PsA patients, those from patients with nonradiographic axial SpA, and those from AS patients. HLA–B27 positivity was similar in PsA patients (10 of 33) and patients with nonradiographic axial SpA (10 of 24) and higher in AS patients (18 of 19). Total MRI scores (L‐spine plus SI joints) were higher in AS patients than in PsA patients (P = 0.025) or in patients with nonradiographic axial SpA (P = 0.007). A relationship was seen between the severity and extent of disease and HLA–B27 positivity in PsA patients, which was comparable to that in AS patients. HLA–B27–negative PsA patients had lower MRI scores than HLA–B27–positive PsA patients (P = 0.03) and AS patients (P = 0.006), whereas scores were similar in HLA–B27–positive PsA patients and AS patients. Similarly, MRI scores of HLA–B27–negative patients with nonradiographic axial SpA were lower than those of AS patients (P = 0.01).

Conclusion

HLA–B27 positivity defines a group of patients with more severe axial bone marrow edema that is likely related to the classic AS phenotype. Clinically, HLA–B27–negative PsA is more likely to be reported as a “negative” MRI examination result.
2,3,17,18‐Tetrahalohexaphyrins and the First Phlorin‐type Hexaphyrins
Authors: Higashino Tomohiro , Osuka Atsuhiro
Published: June 2013

1‐(Triisopropylsilyl)‐3,4‐dichloropyrrole and 1‐(triisopropylsilyl)‐3,4‐difluoropyrrole were conveniently prepared from the corresponding 3,4‐dibromopyrrole by lithiation followed by halogenation. 2,3,17,18‐Tetrahalogeno [26]‐ and [28]hexaphyrins have been prepared by condensation of 3,4‐dihalopyrroles and a dipyrromethane‐dicarbinol. 2,3,17,18‐Tetrahalogenated hexaphyrins display variable structural and electronic properties depending upon the halogen atom and the number of π‐electrons. Tetrabromo[28]hexaphyrin and tetrachloro[28]hexaphyrin were further reduced with excess NaBH4 to furnish meso‐reduced hexaphyrins as the first example of phlorin‐type meso‐aryl‐substituted hexaphyrins.
One‐Pot Multistep Cascade Reactions over Multifunctional Nanocomposites with Pd Nanoparticles Supported on Amine‐Modified Mesoporous Silica
Authors: Li Ping , Liu Hua , Yu Yu , Cao Chang‐Yan , Song Wei‐Guo
Published: June 2013

Two kinds of multifunctional nanocomposites, SBA‐15‐NH2/Pd‐p and SBA‐15‐NH2/Pd‐f, with platelet‐like and fiber‐like morphologies, respectively, were fabricated by immobilizing Pd NPs onto amine‐functionalized SBA‐15. Some of the amino groups acted as anchoring sites for Pd NPs, whilst the remaining groups acted as Brønsted basic sites. As a result, the composites served as excellent multifunctional heterogeneous catalysts for one‐pot multistep cascade reaction sequences. Moreover, when diffusion was the rate‐determine step, SBA‐15‐NH2/Pd‐p, with small mesopores, was superior to the fiber‐like control sample, owing to its short diffusion length, a lower possibility of pore clogging, and better mass transportation for the reaction species during the catalysis.
Modulation of Multifunctional N,O,P Ligands for Enantioselective Copper‐Catalyzed Conjugate Addition of Diethylzinc and Trapping of the Zinc Enolate
Authors: Ye Fei , Zheng Zhan‐Jiang , Deng Wen‐Hui , Zheng Long‐Sheng , Deng Yuan , Xia Chun‐Gu , Xu Li‐Wen
Published: June 2013

In this work, we have successfully synthesized a new family of chiral Schiff base–phosphine ligands derived from chiral binaphthol (BINOL) and chiral primary amine. The controllable synthesis of a novel hexadentate and tetradentate N,O,P ligand that contains both axial and sp3‐central chirality from axial BINOL and sp3‐central primary amine led to the establishment of an efficient multifunctional N,O,P ligand for copper‐catalyzed conjugate addition of an organozinc reagent. In the asymmetric conjugate reaction of organozinc reagents to enones, the polymer‐like bimetallic multinuclear CuZn complex constructed in situ was found to be substrate‐selective and a highly excellent catalyst for diethylzinc reagents in terms of enantioselectivity (up to >99 % ee). More importantly, the chirality matching between different chiral sources, C2‐axial binaphthol and sp3‐central chiral phosphine, was crucial to the enantioselective induction in this reaction. The experimental results indicated that our chiral ligand (R,S,S)‐L1‐ and (R,S)‐L4‐based bimetallic complex catalyst system exhibited the highest catalytic performance to date in terms of enantioselectivity and conversion even in the presence of 0.005 mol % of catalyst (S/C=20 000, turnover number (TON)=17 600). We also studied the tandem silylation or acylation of enantiomerically enriched zinc enolates that formed in situ from copper‐L4‐complex‐catalyzed conjugate addition, which resulted in the high‐yield synthesis of chiral silyl enol ethers and enoacetates, respectively. Furthermore, the specialized structure of the present multifunctional N,O,P ligand L1 or L4, and the corresponding mechanistic study of the copper catalyst system were investigated by 31P NMR spectroscopy, circular dichroism (CD), and UV/Vis absorption.
Multi‐objective airport gate assignment problem in planning and operations
Authors: Prem Kumar V. , Bierlaire Michel
Published: June 2013

We consider the assignment of gates to arriving and departing flights at a large hub airport. This problem is highly complex even in planning stage when all flight arrivals and departures are assumed to be known precisely in advance. There are various considerations that are involved while assigning gates to incoming and outgoing flights (such a flight pair for the same aircraft is called a turn) at an airport. Different gates have restrictions, such as adjacency, last‐in first‐out gates and towing requirements, which are known from the structure and layout of the airport. Some of the cost components in the objective function of the basic assignment model include notional penalty for not being able to assign a gate to an aircraft, penalty for the cost of towing an aircraft with a long layover, and penalty for not assigning preferred gates to certain turns.

One of the major contributions of this paper is to provide mathematical model for all these complex constraints that are observed at a real airport. Further, we study the problem in both planning and operations modes simultaneously, and such an attempt is, perhaps, unique and unprecedented. For planning mode, we sequentially introduce new additional objectives to our gate assignment problem that have not been studied in the literature so far—(i) maximization of passenger connection revenues, (ii) minimization of zone usage costs, and (iii) maximization of gate plan robustness—and include them to the model along with the relevant constraints. For operations mode, the main objectives studied in this paper are recovery of schedule by minimizing schedule variations and maintaining feasibility by minimal retiming in the event of major disruptions. Additionally, the operations mode models must have very, very short run times of the order of a few seconds.

These models are then applied to a functional airline at one of its most congested hubs. Implementation is carried out using Optimization Programming Language, and computational results for actual data sets are reported. For the planning mode, analyst perception of weights for the different objectives in the multi‐objective model is used wherever actual dollar value of the objective coefficient is not available. The results are also reported for large, reasonable changes in objective function coefficients. For the operations mode, flight delays are simulated, and the performance of the model is studied. The final results indicate that it is possible to apply this model to even large real‐life problems instances to optimality within short run times with clever formulation of conventional continuous time assignment model. Copyright © 2013 John Wiley & Sons, Ltd.
A differential evolution approach for the vehicle routing problem with backhauls and time windows
Authors: Küçükoğlu İlker , Öztürk Nursel
Published: June 2013

This paper presents a differential evolution algorithm (DEA) to solve a vehicle routing problem with backhauls and time windows (VRPBTW) and applied for a catering firm. VRPBTW is an extension of the vehicle routing problem, which includes capacity and time window constraints. In this problem, customers are divided into two subsets: linehaul and backhaul. Each vehicle starts from a depot and goods are delivered from the depot to the linehaul customers. Goods are subsequently brought back to the depot from the backhaul customers. The objective is to minimize the total distance that satisfies all of the constraints. The problem is formulated using mixed integer programming and solved using DEA. Proposed algorithm is tested with several benchmark problems to demonstrate effectiveness and efficiency of the algorithm and results show that our proposed algorithm can find superior solutions for most of the problems in comparison with the best known solutions. Hence, DEA was carried out for catering firm to minimize total transportation costs. Copyright © 2013 John Wiley & Sons, Ltd.
Folding thermodynamics of the hybrid‐1 type intramolecular human telomeric G‐quadruplex
Authors: Shek Yuen Lai , Noudeh Golamreza Dehghan , Nazari Mozhgan , Heerklotz Heiko , Abu‐Ghazalah Rashid M. , Dubins David N. , Chalikian Tigran V.
Published: June 2013

Guanine‐rich DNA sequences that may form G‐quadruplexes are located in strategic DNA loci with the ability to regulate biological events. G‐quadruplexes have been under intensive scrutiny owing to their potential to serve as novel drug targets in emerging anticancer strategies. Thermodynamic characterization of G‐quadruplexes is an important and necessary step in developing predictive algorithms for evaluating the conformational preferences of G‐rich sequences in the presence or the absence of their complementary C‐rich strands. We use a combination of spectroscopic, calorimetric, and volumetric techniques to characterize the folding/unfolding transitions of the 26‐meric human telomeric sequence d[A3G3(T2AG3)3A2]. In the presence of K+ ions, the latter adopts the hybrid‐1 G‐quadruplex conformation, a tightly packed structure with an unusually small number of solvent‐exposed atomic groups. The K+‐induced folding of the G‐quadruplex at room temperature is a slow process that involves significant accumulation of an intermediate at the early stages of the transition. The G‐quadruplex state of the oligomeric sequence is characterized by a larger volume and compressibility and a smaller expansibility than the coil state. These results are in qualitative agreement with each other all suggesting significant dehydration to accompany the G‐quadruplex formation. Based on our volume data, 432 ± 19 water molecules become released to the bulk upon the G‐quadruplex formation. This large number is consistent with a picture in which DNA dehydration is not limited to water molecules in direct contact with the regions that become buried but involves a general decrease in solute–solvent interactions all over the surface of the folded structure. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 216–227, 2014.
Using probabilistic roadmaps in changing environments
Authors: Rantanen Mika T. , Juhola Martti
Published: June 2013

In this paper, we examine how a path planning problem can be solved in changing environments using probabilistic roadmap planners. A probabilistic roadmap is built in static environment where all obstacles are known in advance, but we show that a roadmap can be built in such a way that it works well even when new obstacles are added to the workspace. However, our experiments show that the roadmap graph must be built carefully. We compare three different methods that are used to decide which edges are added to the roadmap graph to connect the nodes. One of these is a distance‐based method, which we present in this paper. In the tests, we built a roadmap by using only the static obstacles. Then, we added additional obstacles to the environment and tested how well the roadmap still worked. The tests showed that our distance‐based method worked quickly and that it produced roadmaps, which could be used to find a path amid additional obstacles with a high success rate.Copyright © 2013 John Wiley & Sons, Ltd.
Essential‐Oil Composition of the Tunisian Endemic Cypress (Cupressus sempervirens L. var. numidicaTrab.)
Authors: El Hamrouni‐Aschi Kaouther , Larbi Khouja Mohamed , Boussaid Mohamed , Akrimi Noureddine , Toumi Lamjed
Published: June 2013

The essential oils isolated from leaves, wood, and cones of the Tunisian endemic cypress Cupressus sempervirens L. var. numidica Trab. collected from three natural populations were characterized by GC‐FID and GC/MS analyses. In the wood, leaf, and cone oils, 38, 35, and 26 constituents, representing 94.4, 97.8, and 98.5% of the total oil composition, respectively, were identified. Monoterpenes constituted the major fraction of the oils from all organs and for all populations. The oils were found to be of an α‐pinene (64.2%)/δ‐car‐3‐ene (11.1%) chemotype with considerable contents of α‐humulene (3.4%) in the leaf oil, cedrol (2.8%) in the wood oil, and sabinene (3.2%) in the cone oil, respectively. α‐Pinene, δ‐car‐3‐ene, limonene, carvacrol methyl ether, α‐humulene, and α‐amorphene were the main components that differentiated the oils of the three organs in the cypress of Makthar.
Alkaloids from Zephyranthes robustaBaker and Their Acetylcholinesterase‐ and Butyrylcholinesterase‐Inhibitory Activity
Authors: Kulhánková Andrea , Cahlíková Lucie , Novák Zdeněk , Macáková Kateřina , Kuneš Jiří , Opletal Lubomír
Published: June 2013

The bulbs of Zephyranthes robusta (Amaryllidaceae) have been extensively analyzed for their chemical constituents, resulting in the isolation of 13 alkaloids. The chemical structures of the isolated compounds were elucidated by mass‐spectrometric, and 1D‐ and 2D‐NMR spectroscopic experiments. The complete NMR assignments were achieved for hippeastidine. All isolated alkaloids were evaluated for their erythrocytic acetylcholinesterase and serum butyrylcholinesterase inhibitory activities using the Ellman's method. Significant acetylcholinesterase inhibition activity was exhibited by 8‐O‐demethylmaritidine (IC50(HuAChE) 28.0±0.9 μM).
Bioactive Brominated Metabolites from the Natural Habitat and Tank‐Maintained Cuttings of the Jamaican Sponge Aplysina fistularis
Authors: Gallimore Winklet A.
Published: June 2013

Cut specimens of the common reef sponge of the Verongid family, Aplysina fistularis, were retained in flow‐through seawater tanks over a six‐week period to assess the metabolite profile of the sponge when subjected to stress, compare the profile with the source material, and assess the preliminary feasibility of the protocol for sponge culture. The living specimens were harvested, extracted with MeOH/CH2Cl2 1 : 1, and subjected to column chromatography to identify metabolites. The brominated isoxazoline compounds, aerothionin (1) and 11‐oxoaerothionin (2), along with aeroplysinin 2 (3) and 2‐(3,5‐dibromo‐4‐hydroxyphenol)acetamide (4), were detected in the cuttings from the tank‐maintained sponge. An examination of the metabolite profile of the sponge from the natural habitat showed that the compounds 1 and 2 were present. The identities of all the compounds were ascertained by analysis of the mass‐spectral data and NMR spectra (1H, 13C, HMBC, and HSQC) of the compounds, which were compared with reported data. The survival rate was 44% with limited necrosis or exposed skeletal tissue being observed in eight of the 18 cuttings, suggesting that protocol modifications would be required for culturing the sponge.
Molluscicidal and Leishmanicidal Activity of the Leaf Essential Oil of Syzygium cumini (L.) Skeels from Brazil
Authors: Dias Clarice N. , Rodrigues Klinger A. F. , Carvalho Fernando A. A. , Carneiro Sabrina M. P. , Maia Jose G. S. , Andrade Eloisa H. A. , Moraes Denise F. C.
Published: June 2013

The chemical composition and biological potential of the essential oil extracted from Syzygium cumini leaves collected in Brazil were examined. GC/MS Analyses revealed a high abundance of monoterpenes (87.12%) in the oil. Eleven compounds were identified, with the major components being α‐pinene (31.85%), (Z)‐β‐ocimene (28.98%), and (E)‐β‐ocimene (11.71%). To evaluate the molluscicidal effect of the oil, it was tested against Biomphalaria glabrata and the LC50 obtained was 90 mg/l. The essential oil also showed significant activity against Leishmania amazonensis, with an IC50 value equal to 60 mg/l. In addition, to evaluate its toxicity towards a non‐target organism, the essential oil was tested against Artemia salina and showed a LC50 of 175 mg/l. Thus, the essential oil of S. cumini showed promising activity as a molluscicidal and leishmanicidal agent and might be valuable in combating neglected tropical diseases such as schistosomiasis and leishmaniasis. Further research is being conducted with regard to the purification and isolation of the most active essential‐oil compounds.
Chemodiversity of Ursane‐ and Oleanane‐Type Triterpenes in Amazonian Burseraceae Oleoresins
Authors: Rüdiger André L. , Veiga‐Junior Valdir F.
Published: June 2013

The oleoresins exuded from species of the Burseraceae family present high potential due to their biological and pharmacological properties. The evaluation of the chemodiversity of the oleoresins of 23 Amazonian species of Burseraceae provided a profile of the principal constituents, viz., the ursane‐type triterpenes α‐amyrin (1), α‐amyrenone (3), and brein (5) and the oleanane‐type triterpenes β‐amyrin (2), β‐amyrenone (4), and maniladiol (6), and allowed to determine which of these species have the highest biotechnological potential and which ones are rich in other, potentially new, triterpenes or volatile compounds of interest for the cosmetics industry. The oleoresin compositions obtained by GC‐FID and GC/MS analyses were submitted to principal component analysis (PCA) and hierarchical clustering on principal components (HCPC), which divided the 23 samples in five clusters. Protium giganteum and Trattinnickia peruviana, constituting the first cluster, presented high oleoresin contents of 3 and 4 (28.8 and 16.3% on average, resp.). The seven species of Burseraceae composing the second cluster were potential producers of new triterpenes and volatile compounds. Dacryodes hopkinsii and five Protium species (third cluster) presented average contents for all the triterpenes analyzed. The highest contents of 5 and 6 (averages of 3.9 and 5.4%, resp.) were observed in P. heptaphyllum ssp. ullei and T. glaziovii (fourth cluster). Finally, the six Protium species forming the fifth cluster showed high contents of 1 and 2 (48.0 and 19.9% on average, resp.). Moreover, this study allowed the description of the triterpene composition of 13 not previously investigated species.
Spectroscopic and Biological Studies of Phenanthroline Compounds: Selective Recognition of Gene‐Promoter G‐Quadruplex DNAs Preferred over Duplex DNA
Authors: Wang Lihua , Wei Chunying
Published: June 2013

G‐Quadruplex DNA formed in the promoter regions of proto‐oncogenes would block the transcription process and eventually suppress the development of tumors, so compounds that stabilize G‐quadruplex DNA are potential antitumor drugs. This article describes the interactions of three phenanthroline compounds, a–c, with proto‐oncogene c‐kit2 and c‐myc G‐quadruplex DNAs by means of polymerase chain reaction (PCR) stop assay, fluorescence resonance energy transfer melting (FRET melting) assay, fluorescence indicator displacement (FID) assay, UV/VIS absorption, fluorescence, and circular dichroism (CD) spectroscopies. All three compounds displayed selectivity for the G‐quadruplex over duplex, with binding constants (Ka) for the both quadruplexes varying from 0.49×106 to 3.32×106 M−1 (4.1‐ to 33.2‐fold specificity). Compounds a, b, and c were potential stabilizers for the c‐kit2 G‐quadruplex with the melting‐temperature increase (ΔTm) values of 12–15°. CD Spectra indicated that a–c disrupted the structure of c‐kit2 G‐quadruplex, whereas no significant change was observed for c‐myc G‐quadruplex.
Dodecyl α‐L‐Rhamnopyranosyl‐(1→2)‐β‐D‐fucopyranoside Derivatives from the Glandular Trichome Exudate of Erodium pelargoniflorum
Authors: Sakai Takaomi , Tanemura Yuhei , Itoh Satsuki , Fujimoto Yoshinori
Published: June 2013

Chemical investigation of the glandular trichome exudate of Erodium pelargoniflorum (Geraniaceae) led to the isolation of two dodecyl disaccharide derivatives, named pelargoside A1 and pelargoside B1 (1 and 2, resp.). The structures of 1 and 2 were determined as dodecyl 4‐O‐acetyl‐α‐L‐rhamnopyranosyl‐(1→2)‐4‐O‐acetyl‐β‐D‐fucopyranoside and dodecyl 3,4‐di‐O‐acetyl‐α‐L‐rhamnopyranosyl‐(1→2)‐4‐O‐acetyl‐β‐D‐fucopyranoside, respectively, by spectroscopic studies, including 2D‐NMR, and chemical transformations. In addition, undecyl, tridecyl, and tetradecyl homologs of 1 and 2, named pelargosides A2–A4 and pelargosides B2–B4, were also characterized as minor constituents of the exudate.
From Dioxygen Storing to Dioxygen Sensing with Neuroglobins: An Insight from Molecular Mechanics
Authors: Pietra Francesco
Published: June 2013

This work deals with two neuroglobins from phylogenetically distant organisms. Deriving from the acoelomorph Symsagittifera roscoffensis, SrNgb is functionally pentacoordinated, and is assumed to function as a reserve of dioxygen (O2). Obtained from mice, mNgb is functionally hexacoordinated, and presumably triggers signals from sensing O2. Here, it is investigated how these two globins are permeated by diatomic gases, SrNgb by O2 and mNgb by CO. With protein atomic coordinates available from high‐resolution X‐ray diffraction analysis, O2 and CO pathways were traced from molecular‐dynamics simulations in H2O solution, which makes no difference between the two gases, accelerated by applying an external randomly‐oriented minimal force to the center of mass of the diatomic gas molecule. This allowed us to explore a statistically significant large number of trajectories. It emerged that CO leaves mNgb from preferentially peripheral gates located on the side of the heme propionate chains, whereas O2 leaves SrNgb from the opposite side. This shows no analogy with either the functionally pentacoordinated, O2‐transporting, myoglobin (Mgb), or the hexacoordinated, O2‐sensing, cytoglobin, despite the same three‐over‐three typical α‐helical globin folding. The sole analogy that could be observed was a preference for the shortest diatomic gas pathways with both SrNgb and Mgb. It is tempting to speculate that this fulfills the need of being quick in delivering O2 to depleted organs.
Chemical Tools for Studying the Biological Function of Glycolipids
Authors: Stocker Bridget L. , Timmer Mattie S. M.
Published: June 2013

Glycolipids play an important role in many biological processes and to this end, synthetic chemists have developed a variety of new techniques and “chemical tools” that allow for the study of glycolipids in vitro and in vivo. The types of probes prepared include fluorescent, radio‐labelled, biotinylated and photoreactive ones, as well as others based on liposomes, microarrays and other supramolecular constructs—each of which offers its own advantages, as is discussed. A number of more specialised probes, such as metabolically engineered glycolipids and photopolymerisable glycolipids, have also been prepared in order to investigate various processes including substrate specificities and binding interactions.

The purpose of this review is to present the key approaches that can be used for the development of glycolipid probes, organised according to application, and also to discuss the limitations of such strategies, which include the nontrivial task of ensuring that the probe does not adversely influence the biological activity of the parent compound. On the whole, it is exciting to see what can be achieved through the development of chemical probes as tools to study biological processes, and it is envisioned that the reader will be inspired by the large number of superb studies highlighted here and will be encouraged to undertake further work in this research area.
The TEAD4–YAP/TAZ Protein–Protein Interaction: Expected Similarities and Unexpected Differences
Authors: Hau Jean Christophe , Erdmann Dirk , Mesrouze Yannick , Furet Pascal , Fontana Patrizia , Zimmermann Catherine , Schmelzle Tobias , Hofmann Francesco , Chène Patrick
Published: June 2013

The Hippo pathway controls cell homeostasis, and its deregulation can lead to human diseases. In this pathway, the YAP and TAZ transcriptional cofactors play a key role in stimulating gene transcription through their interaction with the TEAD transcriptional factors. Our study of YAP and TAZ peptides in biochemical and biophysical assays shows that both proteins have essentially the same affinity for TEAD. Molecular modeling and structural biology data suggest that they also bind to the same site on TEAD. However, this apparent similarity hides differences in the ways in which the two proteins interact with TEAD. The secondary structure elements of their TEAD binding site do not contribute equally to the overall affinity, and critical interactions with TEAD are made through different residues. This convergent optimization of the YAP/TAZ TEAD binding site suggests that the similarity in the affinities of binding of YAP to TEAD and of TAZ to TEAD is important for Hippo pathway functionality.
Pseudo‐Fivefold Diffraction Symmetries in Tetrahedral Packing
Authors: Lee Stephen , Henderson Ryan , Kaminsky Corey , Nelson Zachary , Nguyen Jeffers , Settje Nick F. , Schmidt Joshua Teal , Feng Ji
Published: June 2013

We review the way in which atomic tetrahedra composed of metallic elements pack naturally into fused icosahedra. Orthorhombic, hexagonal, and cubic intermetallic crystals based on this packing are all shown to be united in having pseudo‐fivefold rotational diffraction symmetry. A unified geometric model involving the 600‐cell is presented: the model accounts for the observed pseudo‐fivefold symmetries among the different Bravais lattice types. The model accounts for vertex‐, edge‐, polygon‐, and cell‐centered fused‐icosahedral clusters. Vertex‐centered and edge‐centered types correspond to the well‐known pseudo‐fivefold symmetries in Ih and D5h quasicrystalline approximants. The concept of a tetrahedrally‐packed reciprocal space cluster is introduced, the vectors between sites in this cluster corresponding to the principal diffraction peaks of fused‐icosahedrally‐packed crystals. This reciprocal‐space cluster is a direct result of the pseudosymmetry and, just as the real‐space clusters, can be rationalized by the 600‐cell. The reciprocal space cluster provides insights for the Jones model of metal stability. For tetrahedrally‐packed crystals, Jones zone faces prove to be pseudosymmetric with one another. Lower and upper electron per atom bounds calculated for this pseudosymmetry‐based Jones model are shown to accord with the observed electron counts for a variety of Group 10–12 tetrahedrally‐packed structures, among which are the four known Cu/Cd intermetallic compounds: CdCu2, Cd3Cu4, Cu5Cd8, and Cu3Cd10. The rationale behind the Jones lower and upper bounds is reviewed. The crystal structure of Zn11Au15Cd23, an example of a 1:1 MacKay cubic quasicrystalline approximant based solely on Groups 10–12 elements is presented. This compound crystallizes in Im$\bar 3$ (space group no. 204) with a=13.842(2) Å. The structure was solved with R1=3.53 %, I>2σ;=5.33 %, all data with 1282/0/38 data/restraints/parameters.
On the Entangled Growth of NaTaO3 Cubes and Na2Ti3O7 Wires in Sodium Hydroxide Solution
Authors: Baumann Stefan O. , Liu Chang , Elser Michael J. , Sternig Andreas , Siedl Nicolas , Berger Thomas , Diwald Oliver
Published: June 2013

The entangled growth of sodium titanate Na2Ti3O7 nanowires and sodium tantalate NaTaO3 cubes was investigated with electron microscopy, X‐ray diffraction, and UV diffuse reflectance spectroscopy. Depending on the composition of the Ta2O5‐ and TiO2‐particle‐based powder mixtures, which served as educts, we observed different types of hybridization effects. These include the titanium‐induced contraction of the NaTaO3 perovskite‐type unit cell and the generation of electronic defect states in NaTaO3 that give rise to optical subbandgap transitions and tantalum‐induced limitations of the Na2Ti3O7 nanowire growth. The transformation from Ta2O5 to NaTaO3 occurs through a dissolution–recrystallization process. A systematic analysis of the impact of different titanium sources on NaTaO3 dispersion and, thus, on the properties of the entangled nanostructures revealed that a perfect intermixture of cubes and nanowires can only be achieved when titanate nanosheets emerge during transformation as reaction intermediates and shield nucleation and growth of isolated NaTaO3 cubes. The here demonstrated approach can be highly instrumental for understanding the nucleation and growth of composite and entangled nanostructures in solution and—at the same time—provides an interesting new class of photoactive composite materials.
Energy Transfer at the Single‐Molecule Level: Synthesis of a Donor–Acceptor Dyad from Perylene and Terrylene Diimides
Authors: Kim Ha Na , Puhl Larissa , Nolde Fabian , Li Chen , Chen Long , Basché Thomas , Müllen Klaus
Published: June 2013

In 2004, we reported single‐pair fluorescence resonance energy transfer (spFRET), based on a perylene diimide (PDI) and terrylene diimide (TDI) dyad (1) that was bridged by a rigid substituted para‐terphenyl spacer. Since then, several further single‐molecule‐level investigations on this specific compound have been performed. Herein, we focus on the synthesis of this dyad and the different approaches that can be employed. An optimized reaction pathway was chosen, considering the solubilities, reactivities, and accessibilities of the building blocks for each individual reaction whilst still using established synthetic techniques, including imidization, Suzuki coupling, and cyclization reactions. The key differentiating consideration in this approach to the synthesis of dyad 1 is the introduction of functional groups in a nonsymmetrical manner onto either the perylene diimide or the terrylene diimide by using imidization reactions. Combined with well‐defined purification conditions, this modified approach allows dyad 1 to be obtained in reasonable quantities in good yield.
Sequence‐Selective DNA Recognition with Peptide–Bisbenzamidine Conjugates
Authors: Sánchez Mateo I. , Vázquez Olalla , Vázquez M. Eugenio , Mascareñas José L.
Published: June 2013

Transcription factors (TFs) are specialized proteins that play a key role in the regulation of genetic expression. Their mechanism of action involves the interaction with specific DNA sequences, which usually takes place through specialized domains of the protein. However, achieving an efficient binding usually requires the presence of the full protein. This is the case for bZIP and zinc finger TF families, which cannot interact with their target sites when the DNA binding fragments are presented as isolated monomers. Herein it is demonstrated that the DNA binding of these monomeric peptides can be restored when conjugated to aza‐bisbenzamidines, which are readily accessible molecules that interact with A/T‐rich sites by insertion into their minor groove. Importantly, the fluorogenic properties of the aza‐benzamidine unit provide details of the DNA interaction that are eluded in electrophoresis mobility shift assays (EMSA). The hybrids based on the GCN4 bZIP protein preferentially bind to composite sequences containing tandem bisbenzamidine–GCN4 binding sites (TCAT⋅AAATT). Fluorescence reverse titrations show an interesting multiphasic profile consistent with the formation of competitive nonspecific complexes at low DNA/peptide ratios. On the other hand, the conjugate with the DNA binding domain of the zinc finger protein GAGA binds with high affinity (KD≈12 nM) and specificity to a composite AATTT⋅GAGA sequence containing both the bisbenzamidine and the TF consensus binding sites.
Study of hybrid drag models for predicting hydrodynamic behaviour in a spouted bed
Authors: Santos Dyrney A. , Petri Irineu J. , Duarte Claudio R. , Barrozo Marcos A. S.
Published: June 2013

A hybridisation study of drag models was performed in a conical–cylindrical spouted bed by means of CFD simulations using an Eulerian–Eulerian multiphase model. In order to evaluate the simulation results, time‐averaged velocity distributions of the particulate phase were compared with the experimental data obtained by means of an optical fibre probe. The hybrid drag model considering both the volume fraction and the granular temperature distribution in the drag force calculation predicted the experimental data of the particle velocity distribution better than the other simulations performed in this work using other hybrid drag models.
EGFR mutations detected on cytology samples by a centralized laboratory reliably predict response to gefitinib in non–small cell lung carcinoma patients
Authors: Malapelle Umberto , Bellevicine Claudio , De Luca Caterina , Salatiello Maria , De Stefano Alfonso , Rocco Danilo , de Rosa Nicla , Vitiello Fabiana , Russo Stefania , Pepe Francesco , Iaccarino Antonino , Micheli Pietro , Illiano Alfonso , Carlomagno Chiara , Piantedosi Franco Vito , Troncone Giancarlo
Published: June 2013

BACKGROUND

Epidermal growth factor receptor (EGFR) mutations are reliably detected by referral laboratories, even if most lung cancer cytology specimens sent to such laboratories contain very few cells. However, EGFR mutations may be distributed heterogeneously within tumors, thereby raising concerns that mutations detected on cytology are not representative of the entire tumor and, thus, are less reliable in predicting response to tyrosine kinase inhibitor (TKI) treatment than mutations detected on histology. To address this issue, the authors reviewed their clinical practice archives and compared the outcome of TKI treatment among patients who were selected by cytology versus patients who were selected by histology.

METHODS

From July 2010 to July 2012, 364 cytology samples and 318 histology samples were received. Exon 19 deletions and the L858R point mutation in exon 21, detected by fragment assay and TaqMan assay, respectively, were confirmed by direct sequencing; discrepancies were resolved by cloning polymerase chain reaction products. The response rate (RR) and progression‐free survival (PFS) at 12 months (range, 3‐34 months) were evaluable in 13 EGFR‐mutated patients who were selected for treatment by cytology and 13 patients who were selected by histology.

RESULTS

The mutation rate was similar in histology samples (8.5%) and cytology samples (8.8%). The RR (54%) and PFS (9.2 months) were similar in histologically selected patients and cytologically selected patients (RR, 62%; PFS, 8.6 months; P = .88). The disease control rate (responsive plus stable disease) was 92% in histologically selected patients and 100% in cytologically selected patients.

CONCLUSIONS

EGFR mutations detected on cytology specimens by a centralized laboratory can predict TKI treatment response equally well as mutations identified on histology samples. Cancer (Cancer Cytopathol) 2013;121:552–560. © 2013 American Cancer Society.
The effect of rifampin on the pharmacokinetics of sirolimus in healthy volunteers
Authors: Tortorici Michael A. , Matschke Kyle , Korth‐Bradley Joan M. , DiLea Cliff , Lasseter Kenneth C.
Published: June 2013

Sirolimus, metabolized primarily by intestinal and hepatic CYP3A4, is a substrate for P‐glycoprotein. CYP3A4 inducers would be expected to decrease sirolimus exposure. This open‐label, nonrandomized study investigated effects of CYP3A4 induction, by rifampin, on sirolimus pharmacokinetics. Healthy volunteers received sirolimus 20 mg on day 1. After washout period, multiple 600‐mg rifampin doses were administered daily for 14 days. On day 9, one 20‐mg sirolimus dose was administered after an overnight fast (≥10 hours). Whole blood samples for sirolimus collected for 144 hours after each dose were analyzed by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters, assessed using noncompartmental methods, were compared using analysis of variance. Geometric mean ratios of Cmax and AUCinf were 29% (90% CI: 26, 32%) and 18% (90% CI: 16, 21%), respectively, with rifampin co‐administration versus sirolimus alone. Corresponding decreases in Cmax and AUC were 71% and 82%, respectively, which would likely cause trough concentrations to fall below the recommended therapeutic range. Mean CL/F increased approximately fivefold with rifampin versus sirolimus alone. Co‐administering sirolimus and potent CYP3A inducers is not recommended. If co‐administration is necessary, dose adjustment and concentration monitoring should be conducted.
Study on Nanobubble Generation: Saline Solution/Water Exchange Method
Authors: Liu Minghuan , Zhao Wanchen , Wang Shuo , Guo Wen , Tang Yuzhao , Dong Yaming
Published: June 2013

In a recently introduced method for nanobubble generation, water is replaced with NaCl solution. It has the same mechanism as alcohol/water exchange: a liquid of higher gas solubility is used to replace one of lower gas solubility. Herein, the opposite process is realized by replacement of saline solutions with water. Interestingly, nanobubbles are also observed by AFM when different concentrations and valences of saline liquids are employed.