bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel approach to predict cetuximab‐induced hypersensitivity reaction: detection of drug‐specific IgE on basophils
Authors: Iwamoto Takuya , Okamoto Akiharu , Ishinaga Hajime , Shimizu Kasumi , Gayle Alberto A. , Arai Naoya , Takeuchi Kazuhiko , Okuda Masahiro
Published: February 2016

Cetuximab is remarkable for the relatively high rate and severity of hypersensitivity reactions (HR) being reported in the literature. Screening for cetuximab‐specific IgE in serum via immunoassay has been found to be useful in preventing HR; however, these tests are known to have a low positive predictive rate. In an attempt to remedy this, we evaluated the interaction between cetuximab and IgE on basophils for predicting severe cetuximab‐induced HR. Twelve head and neck cancer patients were enrolled in this single‐institution study: four with a history of cetuximab‐induced HR and eight with no such history. Cetuximab‐specific and galactose‐α‐1,3‐galactose (α‐gal) specific IgEs in serum were measured in vitro using an enzyme‐linked immunosorbent assay (ELISA). IgE‐cetuximab binding on basophils was also analyzed to evaluate the decrease in cetuximab molecules on basophils after dissociation of IgE from FcεRI. The positive predictive value associated with the presence of cetuximab‐ or α‐gal‐specific IgE in serum was found to be only 0.67, whereas the negative predictive value was 1.00. On the other hand, in all four patients who developed HR, the cetuximab molecules on basophils were decreased significantly due to the dissociation of IgE from basophils (P < 0.05). However, this was not the case in patients who did not develop HR. In conclusion, our results strongly imply that the IgE‐cetuximab interaction on basophils may be key to developing improved methods for predicting severe cetuximab‐induced HR.
The Essential Oil Compositions of Ocimum basilicum from Three Different Regions: Nepal, Tajikistan, and Yemen
Authors: Sharopov Farukh S. , Satyal Prabodh , Ali Nasser A. Awadh , Pokharel Suraj , Zhang Hanjing , Wink Michael , Kukaniev Muhammadsho A. , Setzer William N.
Published: February 2016

The aerial parts of Ocimum basilicum L. were collected from four different geographical locations, Sindhuli and Biratnagar (Nepal), Chormaghzak village (Tajikistan), and Sana'a (Yemen). The essential oils were obtained by hydrodistillation and analyzed by gas chromatography/mass spectrometry. A cluster analysis of 179 essential oil compositions revealed six major chemotypes: Linalool, eugenol, estragole, methyl eugenol, 1,8‐cineole, and geraniol. All four of the basil oils in this study were of the linalool‐rich variety. Some of the basil oils were screened for bioactivity including antimicrobial, cytotoxicity in human cancer cells, brine shrimp lethality, nematicidal, larvicidal, insecticidal, and antioxidant. The basil oils in this study were not notably antibacterial, cytotoxic, antioxidant, nor nematicidal, but were active in the brine shrimp lethality test, and did show larvicidal and insecticidal activities.
Bioprospecting Chemical Diversity and Bioactivity in a Marine Derived Aspergillus terreus
Authors: Adpressa Donovon A. , Loesgen Sandra
Published: February 2016

A comparative metabolomic study of a marine derived fungus (Aspergillus terreus) grown under various culture conditions is presented. The fungus was grown in eleven different culture conditions using solid agar, broth cultures, or grain based media (OSMAC). Multivariate analysis of LC/MS data from the organic extracts revealed drastic differences in the metabolic profiles and guided our subsequent isolation efforts. The compound 7‐desmethylcitreoviridin was isolated and identified, and is fully described for the first time. In addition, 16 known fungal metabolites were also isolated and identified. All compounds were elucidated by detailed spectroscopic analysis and tested for antibacterial activities against five human pathogens and tested for cytotoxicity. This study demonstrates that LC/MS based multivariate analysis provides a simple yet powerful tool to analyze the metabolome of a single fungal strain grown under various conditions. This approach allows environmentally‐induced changes in metabolite expression to be rapidly visualized, and uses these differences to guide the discovery of new bioactive molecules.
Distance Regulated Vesicle Fusion and Docking Mediated by β‐Peptide Nucleic Acid SNARE Protein Analogues
Authors: Sadek Muheeb , Berndt Daniel , Milovanovic Dragomir , Jahn Reinhard , Diederichsen Ulf
Published: February 2016

Artificial SNARE analogues derived from SNARE proteins, which mediate synaptic membrane fusion, are of interest. They mimic the tetrameric α‐helix bundle of the SNARE motif with various bio‐oligomer recognition units. Interaction between complementary oligomers linked to the respective membrane by lipid or peptide anchors leads to proximity of vesicles and to fusion of lipid bilayers. β‐Peptide nucleic acids were introduced as hybrid oligomers with the native SNARE protein transmembrane/linker sequence, in order to evaluate a fusion system that allows distance tuning of approaching membranes. Formation of a four‐base pair β‐PNA double strand with 20 Å length is sufficient for vesicle membrane fusion. Elongation of the recognition β‐PNA duplex in the linker region yielded a 40 Å β‐peptide duplex and provided a vesicle–vesicle distance that only supported hemifusion of vesicle membranes.
Synchronous brain and intravascular B‐cell lymphoma after remission of an adult hemophagocytic syndrome
Authors: Fonseca Válter R. , Espada Eduardo , Geraldes Ruth , Ortiz Santiago , Sousa Rita , Lopez Dolores , Silva Marisa Teixeira , Victorino Rui
Published: February 2016

Key Clinical Message

Hemophagocytic lymphohistiocytosis (HLH) should be considered in the differential diagnosis of adult patients with white matter disease. Brain involvement can be life‐threatening and should prompt aggressive therapy. Even after HLH remission, the possibility of subsequent deterioration due to emergence of an aggressive intravascular lymphoma is highlighted here.
Computational Insight on CO2 Fixation to Produce Styrene Carbonate Assisted by a Single‐Center Aluminum(III) Catalyst and Quaternary Ammonium Salts
Authors: Butera Valeria , Russo Nino , Cosentino Ugo , Greco Claudio , Moro Giorgio , Pitea Demetrio , Sicilia Emilia
Published: February 2016

DFT calculations were used to investigate the cycloaddition reaction of CO2 to styrene oxide for the formation of styrene carbonate. The uncatalyzed process alongside the reactions assisted by tetrabutylammonium bromide (TBAB), the novel nonsymmetrical single‐center aluminum(III) salen–acac hybrid complex (salenac) (Al1cat) and the binary Al1cat/TBAB system were all investigated and for all of them the optimized structures, rate‐determining steps, and lowest energy barrier reaction pathways were intercepted for both gas‐phase and solvent environments. For the catalyzed systems, the reaction mechanism consists of three key elementary steps: 1) epoxy ring opening; 2) CO2 electrophilic attack and 3) intramolecular cyclization. In the presence of Al1cat, the central metal of the catalyst coordinates with an oxygen atom of the epoxide, activating it towards a nucleophilic attack by the halide. An oxyanion species is formed that affords the corresponding cyclic carbonate after reaction with CO2. Our results provide important hints on the cycloaddition of CO2 and epoxides promoted by nonsymmetrical aluminum complex containing a single metal center, and can satisfactorily explain the previous experimental observations allowing the development of more efficient catalysts for organic carbonate production.
Perovskite LaNiO3 Nanocrystals inside SBA‐15 Silica: High Stability and Anti‐Coking Performance in the Pre‐Reforming of Liquefied Petroleum Gas at a Low Steam‐to‐Carbon Molar Ratio
Authors: Hu Yong , Wang Xueguang , Tan Mingwu , Zou Xiujing , Ding Weizhong , Lu Xionggang
Published: February 2016

A high loading of LaNiO3 perovskite nanocrystals (83 wt %) was successfully incorporated inside the ordered mesoporous framework of SBA‐15 silica by a citric acid assisted impregnation method. The obtained LaNiO3/SBA‐15 material produced both La2O3 nanoparticles and metal Ni nanoparticles with intimate contact and highly dispersed in the mesoporous SBA‐15 framework upon reduction with H2, and it showed high activity, high stability, and good anti‐coking ability for the low‐temperature steam reforming of liquefied petroleum gas at a low steam/carbon ratio of 1.0. The excellent performance of the LaNiO3/SBA‐15 material was attributed to the formation of synergistic active sites in the interfacial area, which consisted of metal Ni and La2O2CO3 species, and the confinement effect of the mesoporous structure on the Ni and La2O3 species.
Mechanism of the Accelerated Reduction of an Oxidized Metal Catalyst under Electric Discharge
Authors: Kim Taegyu , Lee Dae Hoon , Jo Sungkwon , Pyun Sung Hyun , Kim Kwan‐Tae , Song Young‐Hoon
Published: February 2016

The front cover artwork for Issue 04/2016 is provided by the Korea Institute of Machinery and Materials and Chosun University. The image shows a novel reaction pathway for the reduction of metal oxide under electric discharge conditions where activated intermediate species desorb without further surface reaction and react with gas‐phase radicals. See the Communication itself at http://dx.doi.org/10.1002/cctc.201500865.
Daldionin, an Unprecedented Binaphthyl Derivative, and Diverse Polyketide Congeners from a Fungal Orchid Endophyte
Authors: Barnes Emma C. , Jumpathong Juangjun , Lumyong Saisamorn , Voigt Kerstin , Hertweck Christian
Published: February 2016

Thailand possesses a rich diversity of orchid species that, in turn, live in symbiosis with a wide variety of fungi. Such endophytes have the potential to produce secondary metabolites with bioactivity against orchid and/or human pathogens. The orchid‐associated fungal strain Daldinia eschscholtzii was found to produce a diverse range of aromatic polyketides including the new naphthalene derivatives daldionin, nodulones B and C, and daldinones F and G along with eight known compounds. Daldionin possesses an unprecedented oxane‐linked binaphthyl ring system. These compounds demonstrate the high diversity of structural variations that are constructed during fungal biosynthesis, and the results include important observations concerning the biosynthesis of binaphthyl derivatives. Daldionin was found to have weak antiproliferative activity against HUVEC and K‐562 cell lines. All but one of the isolated compounds showed moderate antimicrobial activity towards at least one of the four tested microbial strains.
Trianguleniums as Optical Probes for G‐Quadruplexes: A Photophysical, Electrochemical, and Computational Study
Authors: Shivalingam Arun , Vyšniauskas Aurimas , Albrecht Tim , White Andrew J. P. , Kuimova Marina K. , Vilar Ramon
Published: February 2016

Nucleic acids can adopt non‐duplex topologies, such as G‐quadruplexes in vitro. Yet it has been challenging to establish their existence and function in vivo due to a lack of suitable tools. Recently, we identified the triangulenium compound DAOTA‐M2 as a unique fluorescence probe for such studies. This probe's emission lifetime is highly dependent on the topology of the DNA it interacts with opening up the possibility of carrying out live‐cell imaging studies. Herein, we describe the origin of its fluorescence selectivity for G‐quadruplexes. Cyclic voltammetry predicts that the appended morpholino groups can act as intra‐ molecular photo‐induced electron transfer (PET) quenchers. Photophysical studies show that a delicate balance between this effect and inter‐molecular PET with nucleobases is key to the overall fluorescence enhancement observed upon nucleic acid binding. We utilised computational modelling to demonstrate a conformational dependence of intra‐molecular PET. Finally, we performed orthogonal studies with a triangulenium compound, in which the morpholino groups were removed, and demonstrated that this change inverts triangulenium fluorescence selectivity from G‐quadruplex to duplex DNA, thus highlighting the importance of fine tuning the molecular structure not only for target affinity, but also for fluorescence response.
One‐Pot Synthesis of Pomegranate‐Structured Fe3O4/Carbon Nanospheres‐Doped Graphene Aerogel for High‐Rate Lithium Ion Batteries
Authors: He Dafang , Li Lixian , Bai Fengjuan , Zha Chenyang , Shen Liming , Kung Harold H. , Bao Ningzhong
Published: February 2016

A unique hierarchically nanostructured composite of iron oxide/carbon (Fe3O4/C) nanospheres‐doped three‐dimensional (3D) graphene aerogel has been fabricated by a one‐pot hydrothermal strategy. In this novel nanostructured composite aerogel, uniform Fe3O4 nanocrystals (5–10 nm) are individually embedded in carbon nanospheres (ca. 50 nm) forming a pomegranate‐like structure. The carbon matrix suppresses the aggregation of Fe3O4 nanocrystals, avoids direct exposure of the encapsulated Fe3O4 to the electrolyte, and buffers the volume expansion. Meanwhile, the interconnected 3D graphene aerogel further serves to reinforce the structure of the Fe3O4/C nanospheres and enhances the electrical conductivity of the overall electrode. Therefore, the carbon matrix and the interconnected graphene network entrap the Fe3O4 nanocrystals such that their electrochemical function is retained even after fracture. This novel hierarchical aerogel structure delivers a long‐term stability of 634 mA h g−1 over 1000 cycles at a high current density of 6 A g−1 (7 C), and an excellent rate capability of 413 mA h g−1 at 10 A g−1 (11 C), thus exhibiting great potential as an anode composite structure for durable high‐rate lithium‐ion batteries.
Computational Study of Formic Acid Dehydrogenation Catalyzed by AlIII–Bis(imino)pyridine
Authors: Lu Qian‐Qian , Yu Hai‐Zhu , Fu Yao
Published: February 2016

The mechanism of formic acid dehydrogenation catalyzed by the bis(imino)pyridine‐ligated aluminum hydride complex (PDI2−)Al(THF)H (PDI=bis(imino)pyridine) was studied by density functional theory calculations. The overall transformation is composed of two stages: catalyst activation and the catalytic cycle. The catalyst activation begins with O−H bond cleavage of HCOOH promoted by aluminum–ligand cooperation, followed by HCOOH‐assisted Al−H bond cleavage, and protonation of the imine carbon atom of the bis(imino)pyridine ligand. The resultant doubly protonated complex (H,HPDI)Al(OOCH)3 is the active catalyst for formic acid dehydrogenation. Given this, the catalytic cycle includes β‐hydride elimination of (H,HPDI)Al(OOCH)3 to produce CO2, and the formed (H,HPDI)Al(OOCH)2H mediates HCOOH to release H2.
Halide‐Free Synthesis of Hydrochalcogenide Ionic Liquids of the Type [Cation][HE] (E=S, Se, Te)
Authors: Finger Lars H. , Sundermeyer Jörg
Published: February 2016

We present the synthesis and thorough characterization of ionic liquids and organic salts based on hydrochalcogenide HE− (E=S, Se, Te) anions. Our approach is based on halide‐, metal‐, and water‐free decarboxylation of methylcarbonate precursors under acidic conditions, resulting from the easily dissociating reagents H2E. The compounds were characterized by elemental analysis, multinuclear NMR spectroscopy, thermal and single‐crystal XRD analyses. The hydrosulfide salts were investigated with respect to their ability to dissolve elemental sulfur in varying stoichiometry. Thus‐prepared polysulfide ILs were also analyzed by UV/Vis spectroscopy and cyclic voltammetry.
Bis‐tert‐Alcohol‐Functionalized Crown‐6‐Calix[4]arene: An Organic Promoter for Nucleophilic Fluorination
Authors: Jadhav Vinod H. , Choi Wonsil , Lee Sung‐Sik , Lee Sungyul , Kim Dong Wook
Published: February 2016

A bis‐tert‐alcohol‐functionalized crown‐6‐calix[4]arene (BACCA) was designed and prepared as a multifunctional organic promoter for nucleophilic fluorinations with CsF. By formation of a CsF/BACCA complex, BACCA could release a significantly active and selective fluoride source for SN2 fluorination reactions. The origin of the promoting effects of BACCA was studied by quantum chemical methods. The role of BACCA was revealed to be separation of the metal fluoride to a large distance (>8 Å), thereby producing an essentially “free” F−. The synergistic actions of the crown‐6‐calix[4]arene subunit (whose O atoms coordinate the counter‐cation Cs+) and the terminal tert‐alcohol OH groups (forming controlled hydrogen bonds with F−) of BACCA led to tremendous efficiency in SN2 fluorination of base‐sensitive substrates.
Influence of Equilibration Time in Solution on the Inclusion/Exclusion Topology Ratio of Host–Guest Complexes Probed by Ion Mobility and Collision‐Induced Dissociation
Authors: Carroy Glenn , Daxhelet Charlotte , Lemaur Vincent , De Winter Julien , De Pauw Edwin , Cornil Jérôme , Gerbaux Pascal
Published: February 2016

Host–guest complexes are formed by the creation of multiple noncovalent bonds between a large molecule (the host) and smaller molecule(s) or ion(s) (the guest(s)). Ion‐mobility separation coupled with mass spectrometry nowadays represents an ideal tool to assess whether the host–guest complexes, when transferred to the gas phase upon electrospray ionization, possess an exclusion or inclusion nature. Nevertheless, the influence of the solution conditions on the nature of the observed gas‐phase ions is often not considered. In the specific case of inclusion complexes, kinetic considerations must be taken into account beside thermodynamics; the guest ingression within the host cavity can be characterized by slow kinetics, which makes the complexation reaction kinetically driven on the timescale of the experiment. This is particularly the case for the cucurbituril family of macrocyclic host molecules. Herein, we selected para‐phenylenediamine and cucurbit[6]uril as a model system to demonstrate, by means of ion mobility and collision‐induced dissociation measurements, that the inclusion/exclusion topology ratio varies as a function of the equilibration time in solution prior to the electrospray process.
[Cs6Cl][Fe24Se26]: A Host–Guest Compound with Unique Fe–Se Topology
Authors: Valldor Martin , Böhme Bodo , Prots Yurii , Borrmann Horst , Adler Peter , Schnelle Walter , Watier Yves , Kuo Chang Yang , Pi Tun‐Wen , Hu Zhiwei , Felser Claudia , Tjeng Liu Hao
Published: February 2016

The novel host–guest compound [Cs6Cl][Fe24Se26] (I4/mmm; a=11.0991(9), c=22.143(2) Å) was obtained by reacting Cs2Se, CsCl, Fe, and Se in closed ampoules. This is the first member of a family of compounds with unique Fe–Se topology, which consists of edge‐sharing, extended fused cubane [Fe8Se6Se8/3] blocks that host a guest complex ion, [Cs6Cl]5+. Thus Fe is tetrahedrally coordinated and divalent with strong exchange couplings, which results in an ordered antiferromagnetic state below TN=221 K. At low temperatures, a distribution of hyperfine fields in the Mössbauer spectra suggests a structural distortion or a complex spin structure. With its strong Fe–Se covalency, the compound is close to electronic itinerancy and is, therefore, prone to exhibit tunable properties.
Comparing Ullmann Coupling on Noble Metal Surfaces: On‐Surface Polymerization of 1,3,6,8‐Tetrabromopyrene on Cu(111) and Au(111)
Authors: Pham Tuan Anh , Song Fei , Nguyen Manh‐Thuong , Li Zheshen , Studener Florian , Stöhr Meike
Published: February 2016

The on‐surface polymerization of 1,3,6,8‐tetrabromopyrene (Br4Py) on Cu(111) and Au(111) surfaces under ultrahigh vacuum conditions was investigated by a combination of scanning tunneling microscopy (STM), X‐ray photoelectron spectroscopy (XPS) and density functional theory (DFT) calculations. Deposition of Br4Py on Cu(111) held at 300 K resulted in a spontaneous debromination reaction, generating the formation of a branched coordination polymer network stabilized by C−Cu−C bonds. After annealing at 473 K, the C−Cu−C bonds were converted to covalent C−C bonds, leading to the formation of a covalently linked molecular network of short oligomers. In contrast, highly ordered self‐assembled two‐dimensional (2D) patterns stabilized by both Br−Br halogen and Br−H hydrogen bonds were observed upon deposition of Br4Py on Au(111) held at 300 K. Subsequent annealing of the sample at 473 K led to a dissociation of the C−Br bonds and the formation of disordered metal‐coordinated molecular networks. Further annealing at 573 K resulted in the formation of covalently linked disordered networks. Importantly, we found that the chosen substrate not only plays an important role as catalyst for the Ullmann reaction, but also influences the formation of different types of intermolecular bonds and thus, determines the final polymer network morphology. DFT calculations further support our experimental findings obtained by STM and XPS and add complementary information on the reaction pathway of Br4Py on the different substrates.
Determination of the Influence of Side‐Chain Conformation on Glycosylation Selectivity using Conformationally Restricted Donors
Authors: Dharuman Suresh , Crich David
Published: February 2016

The synthesis of a series of conformationally locked mannopyranosyl thioglycosides in which the C6−O6 bond adopts either the gauche,gauche, gauche,trans, or trans,gauche conformation is described, and their influence on glycosylation stereoselectivity investigated. Two 4,6‐O‐benzylidene‐protected mannosyl thioglycosides carrying axial or equatorial methyl groups at the 6‐position were also synthesized and the selectivity of their glycosylation reactions studied to enable a distinction to be made between steric and stereoelectronic effects. The presence of an axial methoxy group at C6 in the bicyclic donor results in a decreased preference for formation of the β‐mannoside, whereas an axial methyl group has little effect on selectivity. The result is rationalized in terms of through‐space stabilization of a transient intermediate oxocarbenium ion by the axial methoxy group resulting in a higher degree of SN1‐like character in the glycosylation reaction. Comparisons are made with literature examples and exceptions are discussed in terms of pervading steric effects layered on top of the basic stereoelectronic effect.
Continuous‐Flow N‐Heterocyclic Carbene Generation and Organocatalysis
Authors: Di Marco Lorenzo , Hans Morgan , Delaude Lionel , Monbaliu Jean‐Christophe M.
Published: February 2016

Two methods were assessed for the generation of common N‐heterocyclic carbenes (NHCs) from stable imidazol(in)ium precursors using convenient and straightforward continuous‐flow setups with either a heterogeneous inorganic base (Cs2CO3 or K3PO4) or a homogeneous organic base (KN(SiMe3)2). In‐line quenching with carbon disulfide revealed that the homogeneous strategy was most efficient for the preparation of a small library of NHCs. The generation of free nucleophilic carbenes was next telescoped with two benchmark NHC‐catalyzed reactions; namely, the transesterification of vinyl acetate with benzyl alcohol and the amidation of N‐Boc‐glycine methyl ester with ethanolamine. Both organocatalytic transformations proceeded with total conversion and excellent yields were achieved after extraction, showcasing the first examples of continuous‐flow organocatalysis with NHCs.
Triptycene‐Roofed Quinoxaline Cavitands for the Supramolecular Detection of BTEX in Air
Authors: Bertani Federico , Riboni Nicolò , Bianchi Federica , Brancatelli Giovanna , Sterner Elizabeth S. , Pinalli Roberta , Geremia Silvano , Swager Timothy M. , Dalcanale Enrico
Published: February 2016

Invited for the cover of this issue are the groups of Enrico Dalcanale at the University of Parma and Timothy M. Swager at Massachusetts Institute of Technology alongside collaborators at the University of Trieste. The image depicts the capture of aromatic hydrocarbons molecules by the ditrypticene quinoxaline cavitand that was employed as fiber coating for solid‐phase microextraction monitoring in air. Read the full text of the article at 10.1002/chem.201504229.
The pursuit of HR outsourcing in an emerging economy: The effects of HRM strategy on HR labour costs
Authors: Abdul‐Halim Hasliza , Che‐Ha Norbani , Geare Alan , Ramayah T.
Published: February 2016

The study examines the relationships among six types of HRM strategies with three categories of outsourcing HR activities to reduce HR labour costs. The data were gathered from a survey questionnaire of 232 manufacturing organizations of which 113 organizations engaged with HR outsourcing. We found that no organization outsourced transformational HR functions and that organizations that espouse cost efficiency, commitment, and conventional HRM strategies tend to outsource traditional HR functions, whereas quality conscious and commitment HRM strategies tend to outsource transactional HR functions. Transactional and traditional HR functions show a significant relationship with a reduction in HR labour costs. Copyright © 2016 ASAC. Published by John Wiley & Sons, Ltd.
p16‐positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high‐risk human papillomavirus or prognosis and implications for the workup of the unknown primary
Authors: McDowell Lachlan J. , Young Richard J. , Johnston Meredith L. , Tan Tze‐Jian , Kleid Stephen , Liu Chen S. , Bressel Mathias , Estall Vanessa , Rischin Danny , Solomon Benjamin , Corry June
Published: February 2016

BACKGROUND

The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear.

METHODS

One hundred forty‐three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high‐risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes.

RESULTS

The median follow‐up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high‐risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08; 95% confidence interval [CI], 0.85‐1.36; P = .528), cancer‐specific (hazard ratio, 1.12; 95% CI, 0.77‐1.64; P = .542), or progression‐free survival (hazard ratio, 1.03; 95% CI, 0.83‐1.29; P = .783). Distant metastasis‐free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status.

CONCLUSIONS

p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High‐risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site. Cancer 2016;122:1201–8. © 2016 American Cancer Society.
Strong Cosmic Censorship for Surface‐Symmetric Cosmological Spacetimes with Collisionless Matter
Authors: Dafermos Mihalis , Rendall Alan D.
Published: February 2016

This paper addresses strong cosmic censorship for spacetimes with self‐gravitating collisionless matter, evolving from surface‐symmetric compact initial data. The global dynamics exhibit qualitatively different features according to the sign of the curvature k of the symmetric surfaces and the cosmological constant Λ. With a suitable formulation, the question of strong cosmic censorship is settled in the affirmative if Λ=0 or k≤0, Λ > 0. In the case Λ > 0, k=1, we give a detailed geometric characterization of possible “boundary” components of spacetime; the remaining obstruction to showing strong cosmic censorship in this case has to do with the possible formation of extremal Schwarzschild–de Sitter‐type black holes. In the special case that the initial symmetric surfaces are all expanding, strong cosmic censorship is shown in the past for all k,Λ. Finally, our results also lead to a geometric characterization of the future boundary of black hole interiors for the collapse of asymptotically flat data: in particular, in the case of small perturbations of Schwarzschild data, it is shown that these solutions do not exhibit Cauchy horizons emanating from i +  with strictly positive limiting area radius.© 2016 Wiley Periodicals, Inc.
Long‐Lived Excited‐State Dynamics of i‐Motif Structures Probed by Time‐Resolved Infrared Spectroscopy
Authors: Keane Páraic M. , Baptista Frederico R. , Gurung Sarah P. , Devereux Stephen J. , Sazanovich Igor V. , Towrie Michael , Brazier John A. , Cardin Christine J. , Kelly John M. , Quinn Susan J.
Published: February 2016

UV‐generated excited states of cytosine (C) nucleobases are precursors to mutagenic photoproduct formation. The i‐motif formed from C‐rich sequences is known to exhibit high yields of long‐lived excited states following UV absorption. Here the excited states of several i‐motif structures have been characterized following 267 nm laser excitation using time‐resolved infrared spectroscopy (TRIR). All structures possess a long‐lived excited state of ∼300 ps and notably in some cases decays greater than 1 ns are observed. These unusually long‐lived lifetimes are attributed to the interdigitated DNA structure which prevents direct base stacking overlap.
Size‐Dependent Electrocatalytic Activity of Free Gold Nanoparticles for the Glucose Oxidation Reaction
Authors: Hebié Seydou , Napporn Teko W. , Morais Cláudia , Kokoh K. Boniface
Published: February 2016

Understanding the fundamental relationship between the size and the structure of electrode materials is essential to design catalysts and enhance their activity. Therefore, spherical gold nanoparticles (GNSs) with a mean diameter from 4 to 15 nm were synthesized. UV/Vis spectroscopy, transmission electron microscopy, and under‐potential deposition of lead (UPDPb) were used to determine the morphology, size, and surface crystallographic structure of the GNSs. The UPDPb revealed that their crystallographic facets are affected by their size and the growth process. The catalytic properties of these GNSs toward glucose electrooxidation were studied by cyclic voltammetry, taking into account the scan rate and temperature effects. The results clearly show the size‐dependent electrocatalytic activity for glucose oxidation reactions that are controlled by diffusion. Small GNSs with an average size of 4.2 nm exhibited high catalytic activity. This drastic increase in activity results from the high specific area and reactivity of the surface electrons induced by their small size. The reaction mechanism was investigated by in situ Fourier transform infrared reflectance spectroscopy. Gluconolactone and gluconate were identified as the intermediate and the final reaction product, respectively, of the glucose electrooxidation.
A case study of cracks in the scientific enterprise: Response to the comments
Authors: Dehmer Matthias , Mowshowitz Abbe
Published: February 2016

This paper presents the authors' responses to comments on their paper “Cracks in the scientific enterprise” which appears in this issue of Complexity. © 2016 Wiley Periodicals, Inc. Complexity 21: 20–22, 2016
Pulsed laser deposition of pure fluoroapatite film without OH groups
Authors: Fujita Naoki , Makino Takayuki , Sakoishi Yasuhiro , Asano Katsuya , Kusunoki Masanobu
Published: February 2016

The relation between O2 pressure and composition in the pulsed‐laser deposition of fluoroapatite was investigated using both on‐axis and off‐axis methods to determine the optimal conditions for obtaining a pure fluoroapatite film without OH groups. Through this, it was found that an O2 pressure of 10 Pa, combined with an off‐axis method, results in P/Ca and F/Ca values (0.6 and 0.2, respectively) that match closely with a stoichiometric composition of Ca10(PO4)6F2. Fourier transform infrared spectroscopy analysis confirmed that this optimized film was almost pure fluoroapatite, with no evidence of any OH groups originating from hydroxyapatite. X‐ray diffraction also revealed that this fluoroapatite film crystallizes with a c‐axis orientation perpendicular to its surface.
Influences of Pulsed Electric Fields on the Gene Expression of Pathogenic Bacteria
Authors: MANABE YUYA , MAETANI MIKI , NAGANO AKIHIKO , TERANISHI KENJI , SHIMOMURA NAOYUKI , TAKAHASHI AKIRA
Published: February 2016

In the biological and medical fields, sterilization using pulsed electric fields or discharges and electroporation have been studied actively in recent years. It is clear that a pulsed electric field has some sort of effect on an organism. At present, however, it is not sufficiently clear what effect occurs and how the mechanism of a pulsed electric field acts on the organism. The effects of pulsed electric fields on ribonucleic acid (RNA) expression in biological cells were studied with the objective of elucidating the bioelectric mechanism. A pulsed electric field was applied to Vibrio parahaemolyticus, a pathogenic bacteria, and the expression of RNAs, specifically thermostable direct hemolysin (TDH), VP1680, and VP1699, which represent pathogenic agents, were analyzed using the polymerase chain reaction (PCR) method. The level of expression of VP1680 increased when a pulsed electric field was applied, and the effect was at a peak when the electric field strength was 14 kV/cm. The electric field strength barely affected the expression of TDH and VP1699. It was found that the effects of the electric field were different among the RNAs. The expression level varied with time when expression was analyzed. These results suggest the possibility of selective control of gene expression by using pulsed electric fields and possible new applications such as the development of functional foods.
Experimental and Computational Study of Unique Tetranuclear µ3‐Chloride and µ‐Phenoxo/Chloro‐Bridged Defective Dicubane Cobalt(II) Clusters
Authors: Hänninen Mikko. M. , Välivaara Juha , Cano Joan , Sillanpää Reijo , Colacio Enrique
Published: February 2016

Two tetranuclear CoII clusters [Co4(L)2(µ3‐Cl)2Cl2] have been prepared by using multidentate diaminobisphenolate ligands. The solid‐state structures of the complexes were determined by single‐crystal X‐ray diffraction. The cores of the cluster compounds can be defined as a two‐vertex‐deficient dicubane geometry (pseudo‐dicubane). In the central unit, the cobalt(II) cations are linked through phenoxide oxygen (outer bridges) and chloride anions (inner bridges), previously unprecedented in this type of cobalt cluster. The magnetic properties were studied by both experimental and computational methods. By using a combination of techniques, we were able to determine the nature and strength of the intramolecular magnetic exchange coupling mediated by the different bridging fragments between the crystallographically different cobalt(II) cations.
Synthesis of a Family of ([SnSe]1+δ)m­([{MoxNb1x}Se2]1+γ)1([SnSe]1+δ)m­({Nbx­Mo1–x}Se2)1 Superlattice ­Heterostructures (m = 0, 1, 2, 3, 4 ­and 0.8 ≤ x ≤ 1)
Authors: Westover Richard D. , Mitchson Gavin , Ditto Jeffrey J. , Johnson David C.
Published: February 2016

A family of multiple‐component heterostructures, ([SnSe]1+δ)m([{MoxNb1–x}Se2]1+γ)1([SnSe]1+δ)m({NbxMo1–x}Se2)1 (m = 0, 1, 2, 3, 4 and 0.8 ≤ x ≤ 1), was self‐assembled from designed amorphous precursors, and their structure and physical properties were characterized. The compounds consist of MoSe2 and NbSe2 layers with metal centers in a trigonal‐prismatic environment interleaved with systematically increasing numbers of SnSe bilayers with a distorted rock salt structure. The extent of alloying of the miscible dichalcogenide constituents decreased from about 20 % for m = 0 to less than 1 % for m = 3 and 4. The decreased alloying with increased SnSe thickness suggests the diffusion lengths of Mo and Nb during self‐assembly are about a nanometer. Resistivity and Hall coefficient measurements show that the electrical transport properties are similar to those of ([SnSe]1+δ)m(NbSe2)1 (m = 1–8) compounds, suggesting that the NbSe2 layer dominates the conductivity and that charge transfer from SnSe reduces the carrier concentration in the NbSe2 layer.
Application of Deep Eutectic Solvents in Promiscuous Lipase‐Catalysed Aldol Reactions
Authors: González‐Martínez Daniel , Gotor Vicente , Gotor‐Fernández Vicente
Published: February 2016

The application of deep eutectic solvents has been demonstrated for the first time in promiscuous lipase‐catalysed aldol reactions. The model reaction between 4‐nitrobenzaldehyde and acetone was examined in depth, with excellent compatibility being found between porcine pancreas lipase and choline chloride/glycerol mixtures for the formation of the aldol product in high yields. The system was compatible with a series of aromatic aldehydes and ketones including acetone, cyclopentanone and cyclohexanone. In some cases, the corresponding α,β‐unsaturated carbonyl compounds were found as minor products. Control experiments demonstrate that the enzymatic preparation was also responsible for a collateral dehydration reaction once the aldol product is formed.
Model Studies towards Functionalized Bisbenzannulated [5,6]‐Spiro­ketals
Authors: Wilsdorf Michael , Lentz Dieter , Reissig Hans‐Ulrich
Published: February 2016

Following up on our previous model studies on the synthesis of simple bisbenzannulated [5,6]‐spiroketals we here report the preparation of new examples of this entity with a variation in their substitution pattern. The regioselective introduction of functional groups in the C‐3 or C‐3′ positions (rubromycin numbering) may either take place prior to the spiroketalization by α‐functionalizations of the ketone moiety of the precursor or in a subsequent step by the nucleophilic substitution of the benzylic hydroxy group of the previously described C‐3‐hydroxylated spiroketal. By applying these methods we could synthesize new methyl‐substituted, hydroxylated, halogenated and amino‐substituted bisbenzannulated [5,6]‐spiroketals in good overall yields.
Diversity Oriented Synthesis of Allocolchicinoids with Fluoro and/or Oxygen Substituent(s) on the C‐Ring from a Single Common Intermediate
Authors: Takubo Keita , Furutsu Kazunori , Ide Takafumi , Nemoto Hiroyuki , Ueda Yuko , Tsujikawa Kazutake , Ikawa Takashi , Yoshimitsu Takehiko , Akai Shuji
Published: February 2016

Allocolchicinoids, with a distinct polyoxygenated dibenzocycloheptane skeleton, attract much attention as potential candidate anticancer drugs. In this study, eight C‐ring fluorinated analogues of allocolchicinoids, seven C‐ring oxygen‐substituted analogues, and known compounds N‐acetylcolchinol and NSC 51046 were synthesized as racemates from a single common intermediate by using either the deoxyfluorination/migration domino reaction or acid‐promoted migration as the key step. Among the products obtained, some of the fluorinated derivatives strongly inhibited the growth of prostate DU145 and pancreas Panc 1 cancer cell lines with efficacy comparable to or better than those of N‐acetylcolchinol and NSC 51046. They were also less toxic against a non‐cancerous cell line than the known compounds were.
Certification of a New Naringenin Reference Material by Coulometric Titrimetry Combined HPLC‐MS
Authors: Yang Dezhi , Zhang Baoxi , Zhang Li , Lu Yang
Published: February 2016

Certified reference material (CRM) is a kind of measuring tool with high accuracy and traceability. CRMs are the important guarantee of accurate and reliable results of analysis methods. They are the medium of international communication of experimental data. CRMs are widely used in various fields and play a pivotal role in analytical science. However, in the characterization of CRMs, available absolute analysis methods are very limited. In this situation, accurate and reliable relative analysis methods should be applied. In this work, coulometric titrimetry (CT) was applied to the characterization of flavone naringenin CRM according to its structure. For further illustration of the principle of CT, high‐performance liquid chromatography tandem mass spectrometry (HPLC‐MS) was utilized to analyze the titration products in detail. As the conclusion of this paper, the advantages and the influence factors of CT were given. Mass balance (MB) method was employed to verify the result of CT, and consistent result was obtained.
A Facile Chemical Synthesis of Cu2O Nanocubes Covered with Co3O4 Nanohexagons for the Sensitive Detection of Glucose
Authors: Velmurgan Sakthi , Devasenathipathy Rajkumar , Chen Shen‐Ming , Wang Sea‐Fue
Published: February 2016

Copper (I) oxide nanocubes (Cu2O NCs) covered with cobalt oxide nanohexagons (Co3O4 NHs) were prepared through simple chemical method. Here, ascorbic acid is used as reducing and capping agent for the synthesis of nanocubes and nanohexagons. Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Energy‐dispersive X‐ray spectroscopy (EDX) and X‐ray diffraction spectroscopy (XRD) were employed to confirm the prepared nanocomposite. Cu2O NCs−Co3O4 NHs nanocomposite is drop cast on the glassy carbon electrode (GCE) for the fabrication of glucose sensor. The fabricated Cu2O NCs−Co3O4 NHs/GCE exhibited a better electrocatalytic activity towards the determination of glucose than that of individually fabricated Cu2O NCs and Co3O4 NHs modified GCE. Our finding exhibited a wide linear range from 1 μM to 5330 μM with LOD of 0.63 towards glucose. In addition, the sensor attained appreciable stability, repeatability and reproducibility. Practicality of the sensor was demonstrated in human serum samples. The main advantages of the fabricated sensor are simple, biocompatible, cost effective, fast response and highly stable electrode surface.
Capturing CO2 Emissions in the Iron Industries using a Magnetite–Iron Mixture
Authors: Kumar Sushant , Drozd Vadym , Durygin Andriy , Saxena Surendra K.
Published: February 2016

We examined a mixture of magnetite (Fe3O4) and iron (Fe) as a possible CO2 sorbent easily applicable for any ironmaking industries. The mixture reacts with CO2 to form siderite (FeCO3). Our experimental results illustrate a capture capacity of 7.98 mmol
 
for the reactant mixture at 200 °C and 10 bar CO2 pressure in 3 h. The results also show that the kinetics of the carbonation reaction vastly depend on the applied temperature and CO2 pressure. The magnetite was completely regenerated by heating siderite at 350 °C under air flow. The proposed set of reactions can be integrated at any ironmaking sites and can provide a potential solution for CO2 capture in the future.
Targeted activation of CREB in reactive astrocytes is neuroprotective in focal acute cortical injury
Authors: Pardo Luis , Schlüter Agatha , Valor Luis M. , Barco Angel , Giralt Mercedes , Golbano Arantxa , Hidalgo Juan , Jia Peilin , Zhao Zhongming , Jové Mariona , Portero‐Otin Manuel , Ruiz Montserrat , Giménez‐Llort Lydia , Masgrau Roser , Pujol Aurora , Galea Elena
Published: February 2016

The clinical challenge in acute injury as in traumatic brain injury (TBI) is to halt the delayed neuronal loss that occurs hours and days after the insult. Here we report that the activation of CREB‐dependent transcription in reactive astrocytes prevents secondary injury in cerebral cortex after experimental TBI. The study was performed in a novel bitransgenic mouse in which a constitutively active CREB, VP16‐CREB, was targeted to astrocytes with the Tet‐Off system. Using histochemistry, qPCR, and gene profiling we found less neuronal death and damage, reduced macrophage infiltration, preserved mitochondria, and rescued expression of genes related to mitochondrial metabolism in bitransgenic mice as compared to wild type littermates. Finally, with meta‐analyses using publicly available databases we identified a core set of VP16‐CREB candidate target genes that may account for the neuroprotective effect. Enhancing CREB activity in astrocytes thus emerges as a novel avenue in acute brain post‐injury therapeutics. GLIA 2016;64:853–874
Dynamic functional network connectivity reveals unique and overlapping profiles of insula subdivisions
Authors: Nomi Jason S. , Farrant Kristafor , Damaraju Eswar , Rachakonda Srinivas , Calhoun Vince D. , Uddin Lucina Q.
Published: February 2016

The human insular cortex consists of functionally diverse subdivisions that engage during tasks ranging from interoception to cognitive control. The multiplicity of functions subserved by insular subdivisions calls for a nuanced investigation of their functional connectivity profiles. Four insula subdivisions (dorsal anterior, dAI; ventral, VI; posterior, PI; middle, MI) derived using a data‐driven approach were subjected to static‐ and dynamic functional network connectivity (s‐FNC and d‐FNC) analyses. Static‐FNC analyses replicated previous work demonstrating a cognition‐emotion‐interoception division of the insula, where the dAI is functionally connected to frontal areas, the VI to limbic areas, and the PI and MI to sensorimotor areas. Dynamic‐FNC analyses consisted of k‐means clustering of sliding windows to identify variable insula connectivity states. The d‐FNC analysis revealed that the most frequently occurring dynamic state mirrored the cognition‐emotion‐interoception division observed from the s‐FNC analysis, with less frequently occurring states showing overlapping and unique subdivision connectivity profiles. In two of the states, all subdivisions exhibited largely overlapping profiles, consisting of subcortical, sensory, motor, and frontal connections. Two other states showed the dAI exhibited a unique connectivity profile compared with other insula subdivisions. Additionally, the dAI exhibited the most variable functional connections across the s‐FNC and d‐FNC analyses, and was the only subdivision to exhibit dynamic functional connections with regions of the default mode network. These results highlight how a d‐FNC approach can capture functional dynamics masked by s‐FNC approaches, and reveal dynamic functional connections enabling the functional flexibility of the insula across time. Hum Brain Mapp 37:1770–1787, 2016. © 2016 Wiley Periodicals, Inc.
Allocation of Residency Training Positions in Spain: Contextual Effects on Specialty Preferences
Authors: Harris Jeffrey E. , Lopez‐Valcarcel Beatriz G. , Barber Patricia , Ortún Vicente
Published: February 2016

In Spain's ‘MIR’ system, medical school graduates are ranked by their performance on a national exam and then sequentially choose from the available residency training positions. We took advantage of a unique survey of participants in the 2012 annual MIR cycle to analyze preferences under two different choice scenarios: the residency program actually chosen by each participant when it came her turn (the ‘real’) and the program that she would have chosen if all residency training programs had been available (the ‘counterfactual’). Utilizing conditional logit models with random coefficients, we found significant differences in medical graduates' preferences between the two scenarios, particularly with respect to three specialty attributes: work hours/lifestyle, prestige among colleagues, and annual remuneration. In the counterfactual world, these attributes were valued preferentially by those nearer to the top, while in the real world, they were valued preferentially by graduates nearer to the bottom of the national ranking. Medical graduates' specialty preferences, which we conclude, are not intrinsically stable but depend critically on the ‘rules of the game’. The MIR assignment system, by restricting choice, effectively creates an externality in which those at the bottom, who have fewer choices, want what those at the top already have. Copyright © 2016 John Wiley & Sons, Ltd.