bluuebunny/crossref_metadata_2025 huggingface dataset:
Ynamide‐Mediated Thiopeptide Synthesis
Authors: Yang Jinhua , Wang Changliu , Xu Silin , Zhao Junfeng
Published: November 2018

Exploration of the full potential of thioamide substitution as a tool in the chemical biology of peptides and proteins has been hampered by insufficient synthetic strategies for the site‐specific introduction of a thioamide bond into a peptide backbone. A novel ynamide‐mediated two‐step strategy for thiopeptide bond formation with readily available monothiocarboxylic acids as thioacyl donors is described. The α‐thioacyloxyenamide intermediates formed from the ynamides and monothiocarboxylic acids can be purified, characterized, and stored. The balance between their activity and stability enables them to act as effective thioacylating reagents to afford thiopeptide bonds under mild reaction conditions. Amino acid functional groups such as OH, CONH2, and indole NH groups need not be protected during thiopeptide synthesis. The modular nature of this strategy enables the site‐specific incorporation of a thioamide bond into peptide backbones in both solution and the solid phase.
Novel palladium nanoparticles supported on β‐cyclodextrin@graphene oxide as magnetically recyclable catalyst for Suzuki–Miyaura cross‐coupling reaction with two different approaches in bio‐based solvents
Authors: Heidari Bahareh , Heravi Majid M. , Nabid Mohammad Reza , Sedghi Roya , Hooshmand Seyyed Emad
Published: November 2018

A novel nanocatalyst was designed and prepared. Initially, the surface of magnetic graphene oxide (M‐GO) was modified using thionyl chloride, tris(hydroxymethyl)aminomethane and acryloyl chloride as linkers which provide reactive C═C bonds for the polymerization of vinylic monomers. Separately, β‐cyclodextrin (β‐CD) was treated with acryloyl chloride to provide a modified β‐CD. Then, in the presence methylenebisacrylamide as a cross‐linker, monomers of modified β‐CD and acrylamide were polymerized on the surface of the pre‐prepared M‐GO. Finally, palladium acetate and sodium borohydride were added to this composite to afford supported palladium nanoparticles. This fabricated nanocomposite was fully characterized using various techniques. The efficiency of this easily separable and reusable heterogeneous catalyst was successfully examined in Suzuki–Miyaura cross‐coupling reactions of aryl halides and boronic acid as well as in modified Suzuki–Miyaura cross‐coupling reactions ofN‐acylsuccinimides and boronic acid in green media. The results showed that the nanocatalyst was efficient in coupling reactions for direct formation of the corresponding biphenyl as well as benzophenone derivatives in green media based on bio‐based solvents. In addition, the nanocatalyst was easily separable, using an external magnet, and could be reused several times without significant loss of activity under the optimum reaction conditions.
CuBr‐catalysed one‐pot multicomponent synthesis of 3‐substituted 2‐thioxo‐2,3‐dihydroquinazolin‐4(1H)‐one derivatives
Authors: Sayahi Mohammad Hosein , Saghanezhad Seyyed Jafar , Bahadorikhalili Saeed , Mahdavi Mohammad
Published: November 2018

A novel methodology is presented for the synthesis of 3‐substituted 2‐thioxo‐2,3‐dihydroquinazolin‐4(1H)‐one derivatives based on an efficient tandem multicomponent reaction using copper bromide as catalyst. This methodology is based on the multicomponent one‐pot reaction of methyl 2‐bromobenzoate, phenylisothiocyanate derivatives and sodium azide in the presence of copper bromide and l‐proline under basic conditions. To show the generality of the method, various phenylisothiocyanates bearing electron‐donating or electron‐withdrawing functionalities were used and the desired products were obtained in high isolated yields.
Solvent effects on catalytic activity of manganese porphyrins with cationic, anionic and uncharged meso substituents: Indirect evidence on the nature of active oxidant species
Authors: Esfandiari bayat Zahra , Rahiminezhad Hajar , Zakavi Saeed
Published: November 2018

Oxidation of cyclohexene and styrene with sodium periodate and tetra‐n‐butylammonium periodate (TBAP) catalyzed by MnT(3‐MePy)P(OAc), MnT(4‐SO3)PP(OAc) and MnTPP(OAc) has been studied in water, methanol, acetonitrile and dichloromethane as solvents. The results show significant dependence of the product distribution on the type of solvent and the electronic nature of the aryl substituents introduced at the porphyrin periphery. While the oxidation of cyclohexene and styrene in the presence of MnT(3‐MePy)P(OAc) and MnTPP(OAc) in water (also in methanol) gave the corresponding epoxides as nearly the sole product, performing the reactions in the presence of MnT(4‐SO3)PP(OAc) yielded the products of allylic oxidation, cyclohexene‐2‐ol and cyclohexene‐2‐one and acetophenone as the major products. In the case of styrene, performing the reaction in the presence of MnT(4‐SO3)PP(OAc), MnT(3‐MePy)P(OAc) and MnTPP(OAc) in acetonitrile gave a mixture of styrene oxide and acetophenone as the products. Under the same conditions, the oxidation of cyclohexene afforded cyclohexene oxide as approximately the exclusive product. Furthermore, the oxidation of olefins in dichloromethane gave the corresponding epoxide as the exclusive products. The product distributions observed in the protic and aprotic solvents were used to provide indirect evidence on the relative contribution and reactivity of high valent manganese oxo and periodato Mn(III) porphyrin species to the oxidation reactions.
Common dolphins in the Gulf of Corinth are Critically Endangered
Authors: Santostasi Nina Luisa , Bonizzoni Silvia , Gimenez Olivier , Eddy Lavinia , Bearzi Giovanni
Published: November 2018

Regional populations (“subpopulations”) of globally abundant species can be exposed to human impacts that threaten their viability. Given the value of cetacean subpopulations as evolutionary significant units, keystone and umbrella species, it is important to assess their conservation status separately and propose area‐specific conservation measures.

We used a threat assessment process and applied IUCN Red List criteria to a regional population of common dolphins Delphinus delphis in the semi‐enclosed Gulf of Corinth, Greece. We compiled subpopulation‐specific information about abundance and trends, estimated the geographic range of the subpopulation (area of occupancy and extent of occurrence), and calculated the probability of extinction through stochastic modelling.

The subpopulation qualified as Endangered according to criteria A (population size reduction over three generations) and B (geographic range), and as Critically Endangered under criteria C (population size and decline) and D (very small or restricted population). The probability of extinction was estimated to be ≥50% in three generations, qualifying the subpopulation as Critically Endangered under criterion E (quantitative analysis). We concluded that the subpopulation should be classified as Critically Endangered.

Considering the high extinction risk faced by common dolphins in the Gulf of Corinth, we recommend that: (a) immediate action is taken to mitigate anthropogenic activities known or suspected to have a negative impact on cetaceans in the area (particularly commercial fishing); and (b) a marine protected area is established in the Gulf of Corinth as a management tool for enforcing conservation action and facilitating the recovery of common dolphins.
Anatomy Teaching, a “Model” Answer? Evaluating “Geoff”, a Painted Anatomical Horse, as a Tool for Enhancing Topographical Anatomy Learning
Authors: Bietzk Edward , Weller Renate , Simons Victoria , Channon Sarah B.
Published: November 2018

Development of new methods for anatomy teaching is increasingly important as we look to modernize and supplement traditional teaching methods. In this study, a life‐sized equine model, “Geoff,” was painted with surface and deep anatomical structures with the aim of improving students’ ability to convert theoretical knowledge into improved topographical anatomy knowledge on the live horse. Third and fourth year veterinary medicine students (n = 45) were randomly allocated into experimental (used “Geoff”) and control (used textbook) groups. The efficacy of the model was evaluated through a structured oral exam using a live horse. Questionnaires gathered information on student confidence and enjoyment of the task. There was no significant difference in the performance of experimental and control groups either immediately (44±20% vs. 40±21%; P = 0.504) or 9 weeks after the learning intervention (55±17% vs. 55±20%; P = 0.980). There were however specific questions on which the experimental group performed better than controls, and for which gender effects were apparent. The students using “Geoff” showed a transient gain in confidence following the session (Likert scale 2.7 to 3.6) however the initial increase was no longer present at the second test. There was a significant influence of gender on confidence with greater confidence gains in females in the Experimental group. The students found the model to be extremely useful and both groups found the sessions enjoyable. The model will be of benefit as a complementary learning tool for students.
Radical Addition/Cyclization Reaction of 2‐Vinylanilines with Alkynes: Synthesis of Naphthalenes via Electron Catalysis
Authors: Cao Xia , Cai Bao‐Gui , Xu Guo‐Yong , Xuan Jun
Published: November 2018

A cascade radical addition/cyclization reaction of 2‐vinylanilines with alkynes for the synthesis of biologically important naphthalene derivatives is reported. In this transformation, the in‐situ‐formed diazonium salts from 2‐vinylanilines served as efficient aryl radical precursors and the reaction was run under metal‐free conditions.
Tunable luminescent properties of BaGd2O4:Eu3+ scintillating phosphors by Pr3+‐codoping
Authors: Sun Xin‐Yuan , Zhu Shou‐Bao , Xiao Fen , Zhou Shen‐Lin , Li Lu‐Nong
Published: November 2018

BaGd2O4:Eu3+ scintillating phosphors by Pr3+‐codoping were synthesized at 1300°C in air using a solid‐state reaction method. The as‐synthesized phosphors were characterized by X‐ray diffraction (XRD), photoluminescence (PL) including excitation and emission spectra, radioluminescence (RL) spectra excited by X‐ray and thermoluminescence (TL) spectra. Both the PL and RL spectra are composed of the featured trivalent europium (Eu3+) without any praseodymium (Pr3+) ions, and the PL and RL intensities as well as the lifetimes of BaGd2O4:Eu3+ scintillating phosphors decrease dramatically with an increasing concentration of Pr3+ ions. Finally, the TL spectra reveal the trap concentration of the existing defects decrease with an increasing concentration of Pr3+ ions, while the relative TL intensity ratio of the high temperature band to the low temperature one increases with an increasing concentration of Pr3+ ions, which results in the afterglow suppression of BaGd2O4:Eu3+ scintillating phosphors.
An ultra scale‐down method to investigate monoclonal antibody processing during tangential flow filtration using ultrafiltration membranes
Authors: Fernandez‐Cerezo Lara , Rayat Andrea C. M. E. , Chatel Alex , Pollard Jennifer M. , Lye Gary J. , Hoare Michael
Published: November 2018

The availability of material for experimental studies is a key constraint in the development of full‐scale bioprocesses. This is especially true for the later stages in a bioprocess sequence such as purification and formulation, where the product is at a relatively high concentration and traditional scale‐down models can require significant volumes. Using a combination of critical flow regime analysis, bioprocess modelling, and experimentation, ultra scale‐down (USD) methods can yield bioprocess information using only millilitre quantities before embarking on highly demanding full‐scale studies. In this study the performance of a pilot‐scale tangential flow filtration (TFF) system based on a membrane flat‐sheet cassette using pumped flow was predicted by devising an USD device comprising a stirred cell using a rotating disc. The USD device operates with just 2.1 cm2of membrane area and, for example, just 1.7 mL of feed for diafiltration studies. The novel features of the design involve optimisation of the disc location and the membrane configuration to yield an approximately uniform shear rate. This is characterised using computational fluid dynamics for a defined layer above the membrane surface. A pilot‐scale TFF device operating at ~500‐fold larger feed volume and membrane area was characterised in terms of the shear rate derived from flow rate‐pressure drop relationships for the cassette. Good agreement was achieved between the USD and TFF devices for the flux and resistance values at equivalent average shear rates for a monoclonal antibody diafiltration stage.
Leading corporate sustainability: The role of top management team composition for triple bottom line performance
Authors: Henry Leona Aimée , Buyl Tine , Jansen Rob J.G.
Published: November 2018

Sustainable development at the corporate level requires balancing social, environmental, and financial performance goals. Achieving such “triple bottom line” (TBL) performance is a very challenging task. In this study, we explore the role the organization's top management team (TMT) plays in leading their organization towards corporate sustainability. We focus on how two distinct aspects of the TMT's structural composition—the presence of a “chief sustainability officer” (CSO) and the TMT's functional diversity—affect the organization's ability to reach high levels of TBL performance. We follow the presence of 22 global energy companies in Corporate Knight's “Global 100” sustainability index for a period of 11 years and find that, surprisingly, the presence of a CSO does not boost TBL performance. However, we do find a positive effect for TMT functional diversity, suggesting that more diverse TMTs are better able to lead their organization to higher levels of TBL performance.
Dysregulated circular RNAs in medulloblastoma regulate proliferation and growth of tumor cells via host genes
Authors: Lv Tao , Miao Yi‐Feng , Jin Ke , Han Shuo , Xu Tian‐Qi , Qiu Zi‐Long , Zhang Xiao‐Hua
Published: November 2018

Circular RNAs (circRNAs) have been demonstrated to be involved in various biological processes. Nevertheless, the function of circRNAs in medulloblastoma (MB) is still unknown. The present study aimed to investigate the expression profiles of circRNAs and related mechanisms for regulating the proliferation and growth of tumor cells in MB. The expression profiles of circRNAs were screened from four normal cerebellum and four MB samples using a HiSeq Sequencer. Bioinformatic analysis was employed to predict the interaction between circRNAs and mRNAs in MB. Subsequently, the expression levels of eight differential circRNAs [circ‐SKA3 (hsa_circ_0029696), circ‐DTL (hsa_circ_0000179), circ‐CRTAM, circ‐MAP3K5 (hsa_circ_0006856), circ‐RIMS1‐1 (hsa_circ_0132250), circ‐RIMS1‐2 (hsa_circ_0076967), circ‐FLT3‐1 (hsa_circ_0100165), and circ‐FLT3‐2 (hsa_circ_0100168)] were validated using quantitative reverse transcription−polymerase chain reaction. Moreover, circ‐SKA3 and circ‐DTL were silenced using small interfering RNAs and their host genes were overexpressed to investigate their role in the pathogenesis of MB. A total of 33 circRNAs were found to be differentially expressed in MB tissues (fold change ≥ 2.0, FDR <0.05), of which three were upregulated and 30 were downregulated; six circRNAs were experimentally validated successfully. Upregulated circ‐SKA3 and circ‐DTL promoted the proliferation migration and invasion in vitro by regulating the expression of host genes. This novel study exploited the profiling of circRNAs in MB and demonstrated that circ‐SKA3 and circ‐DTL were crucial in the tumorigenesis and development of MB and might be considered as novel and potential biomarkers for the diagnosis and new targets for the intervention of MB.
Colloidal Fluorophore Aggregates for the Selective Detection of Albumins in Solution and on Electrophoresis Gels
Authors: Park Jihee , Kim Youngmi
Published: November 2018

We report a fluorescent probe that is highly sensitive and selective for serum albumins. Signal transduction results from the disassembly of fluorescence‐quenched aggregates upon binding to human serum albumin (HSA). The probe offers a rapid (≤2 s) fluorometric assay of HSA in phosphate‐buffered saline, urine, or blood serum with a high signal‐to‐noise ratio. It is also useful as a wash‐free prestaining reagent for detecting HSA on electrophoresis gels.
Concurrent phyllodes tumor, eccrine carcinoma, and multinodular goiter 20 years after radiotherapy for Hodgkin lymphoma
Authors: Quinn Kristen M. , Tozbikian Gary , Carson William E.
Published: November 2018

Key Clinical Message

This unusual case of concurrent eccrine adenocarcinoma, phyllodes tumor, and multinodular goiter serves to alert the oncologic community to the high prevalence of second cancers after childhood radiotherapy. Increased surveillance and index of suspicion are recommended to successfully diagnose and treat second primary cancers in this vulnerable population.
Antioxidant Activity of an Industrial Cupuassu Seed By‐product: Molecular Modeling of Phenolic Compounds
Authors: Silva da Costa Russany , de Farias Silva Natália , Gabbay Alves Taís Vanessa , Fernandes da Silva Milena , do Socorro Barros Brasil Davi , Ribeiro-Costa Roseane Maria , Converti Attilio , Carréra Silva José Otávio
Published: November 2018

To better understand the biological properties of cupuassu seed residue resulting from fruit industrial processing, its antioxidant activity was determined by both the 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) assays. Molecular modeling was used to correlate the antiradical power of eleven known cupuassu phenolic compounds with their structures. The extract antioxidant activity by both methods was very high compared with those of similar residues. The properties of the highest occupied and lowest unoccupied molecular orbitals indicate that the most energetically stable compounds possess the highest antioxidant activity. This was confirmed through the molecular electrostatic potential map by the nucleophilic surfaces on the oxygen atoms of carbonyl and hydroxyl groups.
Origin of the Photoinduced Geometrical Change of Copper(I) Complexes from the Quantum Chemical Topology View
Authors: Gutiérrez‐Arzaluz Luis , Ramírez‐Palma David Ignacio , Ramírez‐Palma Lillian G. , Barquera‐Lozada José Enrique , Peon Jorge , Cortés‐Guzmán Fernando
Published: November 2018

Copper(I) complexes (CICs) are of great interest due to their applications as redox mediators and molecular switches. CICs present drastic geometrical change in their excited states, which interferes with their luminescence properties. The photophysical process has been extensively studied by several time‐resolved methods to gain an understanding of the dynamics and mechanism of the torsion, which has been explained in terms of a Jahn–Teller effect. Here, we propose an alternative explanation for the photoinduced structural change of CICs, based on electron density redistribution. After photoexcitation of a CIC (S0→S1), a metal‐to‐ligand charge transfer stabilizes the ligand and destabilizes the metal. A subsequent electron transfer, through an intersystem crossing process, followed by an internal conversion (S1→T2→T1), intensifies the energetic differences between the metal and ligand within the complex. The energy profile of each state is the result of the balance between metal and ligand energy changes. The loss of electrons originates an increase in the attractive potential energy within the copper basin, which is not compensated by the associated reduction of the repulsive atomic potential. To counterbalance the atomic destabilization, the valence shell of the copper center is polarized (defined by ∇2ρ(r) and ∇2Vne(r)) during the deactivation path. This polarization increases the magnitude of the intra‐atomic nuclear–electron interactions within the copper atom and provokes the flattening of the structure to obtain the geometry with the maximum interaction between the charge depletions of the metal and the charge concentrations of the ligand.
Construction of a DNA‐Based Supramolecular Nanosheet That Emits Bluish‐White Light from Charge‐Transfer Excited States of the Nucleobases
Authors: Iwaura Rika
Published: November 2018

1,ω‐Inosinic acid‐bearing bolaamphiphiles dI(18), dI(19), and dI(20) with a 3′‐phosphorylated inosine as a universal base connected to each end of an oligomethylene chain were synthesized for the first time. Single‐component self‐assemblies of these bolaamphiphiles and their binary self‐assemblies with salmon sperm DNA were studied by AFM; temperature‐dependent UV absorption, fluorescence, and circular dichroism spectroscopy; and gel electrophoresis. The binary self‐assembly of dI(20) and salmon sperm DNA (dI(20)‐DNA) had a nanosheet structure with a homogeneous thickness of about 6 nm and widths of several micrometers. Interestingly, an aqueous solution of the nanosheets showed a broad absorption band originating from the charge‐transfer (CT) states of the nucleobase in the long‐wavelength region (>300 nm), and the molar absorptivity per nucleobase was calculated to be approximately 150 times that of single‐stranded (dT20 and dA20) and double‐stranded (dT20‐dA20) oligonucleotides. In addition, a continuous and broad emission band originating from CT excited states of the nucleobases was observed in the visible region. These observations indicate that CT states of the nucleobases were formed and stabilized in the supramolecular nanosheet and that bluish white light was emitted from CT excited states of the nucleobases.
Phosphorus versus Sulfur: Discovery of Benzenephosphonamidates as Versatile Sulfonamide‐Mimic Chemotypes Acting as Carbonic Anhydrase Inhibitors
Authors: Nocentini Alessio , Gratteri Paola , Supuran Claudiu T.
Published: November 2018

The first zinc‐binding group (ZBG) to have been identified as inhibitor of the metallo‐enzymes carbonic anhydrases (CA, EC 4.2.1.1) was the sulfonamide. From then on several classes of zinc‐binders have been described. This work reports the benzenephosponamidates as a new chiral aromatic sulfonamide‐mimic ZBG able to meet the requirements for effectively binding the enzyme active site. Several low micromolar CA I, II, VII, IX inhibitors were thus detected. Kinetic studies, QM‐polarized ligand docking, and MM‐GBSA in silico methods were used to characterize this newly identified CA inhibitor chemotype.
Single C−F Bond Activation of the CF3 Group with a Lewis Acid: CF3‐Cyclopropanes as Versatile 4,4‐Difluorohomoallylating Agents
Authors: Fuchibe Kohei , Oki Rie , Hatta Hibiki , Ichikawa Junji
Published: November 2018

The selective activation of one C−F bond (single activation) of the CF3 group on cyclopropanes was achieved for the first time. When (trifluoromethyl)cyclopropanes were treated with arenes, allylsilanes, silyl enol ethers, or hydrosilanes in the presence of Me2AlCl, fluoride elimination and the subsequent ring opening proceeded to afford 4,4‐difluorohomoallylated products. In the absence of external nucleophiles, an alkyl group of AlR3 was effectively introduced to provide the corresponding 1,1‐difluoroalkenes.
Porphyrin‐Stabilized Nitrenium Dication
Authors: Fujimoto Keisuke , Shimizu Daiki , Osuka Atsuhiro
Published: November 2018

An azepine‐fused NiII‐porphyrin dimer was synthesized by oxidative amination of β–β linked NiII‐porphyrin dimer, and its N‐aryl congener was synthesized by twofold Buchwald–Hartwig amination of β‐to‐β linked and dichlorinated NiII‐porphyrin dimer. Oxidation of the NH congener gave neutral aminyl radical and nitrenium ion successively in a similar manner to the previously reported NH‐bridged NiII‐porphyrin dimer. Oxidation of the N‐aryl congener afforded formal nitrenium dication in a single‐step two‐electron oxidation. Stable nitrenium dications that are isoelectronic to neutral trivalent boron compounds and tertiary carbocations are rare. The chemical stability of the nitrenium dication was improved by chlorine substitution at the most reactive β‐position. The structural, optical, magnetic, electrochemical properties of these compounds were fully characterized.
Atopic dermatitis as Th2 disease revisited
Authors: Tokura Yoshiki , Phadungsaksawasdi Pawit , Ito Taisuke
Published: November 2018

T helper 1 (Th1) and T helper 2 (Th2) populations are a classical dichotomy to understand the immunological disorders, and this concept remains vital in atopic dermatitis (AD). While IL‐4 and IL‐13 are produced mainly by Th2 cells, mast cells, and basophils, these cytokines target these producers, indicating the presence of autocrine and paracrine stimulation. There are two types of receptors for IL‐4 and IL‐13, type I and type II. IL‐4 binds to both type I and II receptors, while IL‐13 has affinity to type II. Dupilumab is an IL‐4Rα‐antagonist that inhibits IL‐4 and IL‐13 signaling through blockade of the shared IL‐4α subunit. The Th2‐stimulating effect of thymic stromal lymphopoietin (TSLP) is triggered by its binding to TSLP receptor (TSLPR) on Th2 cells. The frequency of TSLPR+CD4+ T cells correlates with disease activity. CD4+ T cells directly interact with TSLP to produce a high amount of IL‐4. Conversely, IL‐4 induces TSLPR expression in T cells. Moreover, TSLP and IL‐4 promote CCR4 expression, which is a chemokine receptor for CCL17/TARC. Langerhans cells initiate epicutaneous sensitization with protein antigens and induce Th2 cell–mediated immune responses via TSLP signaling. Filaggrin deficiency, which cornified layer‐damaged skin allows protein antigens to penetrate through the stratum corneum, leads to allergy where IL‐4 and IL‐13 are overproduced. Subsequently, IL‐4 and IL‐13 further depress filaggrin expression with vicious cycle. AD is generally a Th2 disease, but there exist several exceptional and undeniable facts to be considered, including Th1‐activated intrinsic AD, Th1‐infiltrating chronic AD skin lesions, and Th17 involvement.
Bioequivalence of the Once‐Daily Single‐Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability
Authors: Crauwels Herta M. , Baugh Bryan , Van Landuyt Erika , Vanveggel Simon , Hijzen Anja , Opsomer Magda
Published: November 2018

The effect of food on the bioavailability of the components of the once‐daily, single‐tablet human immunodeficiency virus (HIV) type 1 regimen containing darunavir (DRV 800 mg), cobicistat (COBI 150 mg), emtricitabine (FTC 200 mg), and tenofovir alafenamide (TAF 10 mg) (D/C/F/TAF) (NCT02475135) and the bioequivalence of D/C/F/TAF versus combined intake of the separate agents (NCT02578550) were evaluated. These were 2 phase 1, open‐label, randomized, 2‐period crossover studies (7‐day washout between treatments) in HIV‐negative healthy volunteers. Twenty‐four participants each received a single dose of D/C/F/TAF in fasted conditions (test) or after a standardized high‐fat breakfast (reference). Ninety‐six participants each received a single dose of D/C/F/TAF (test) or combined intake of a single DRV 800‐mg tablet, a COBI 150‐mg tablet, and an FTC/TAF 200/10‐mg tablet (reference), both after a standardized regular‐calorie, regular‐fat breakfast. Pharmacokinetic profiles for all D/C/F/TAF components, safety, and tolerability were assessed. Following D/C/F/TAF in fasted conditions, DRV peak concentration, area under the concentration‐time curve from time of administration until the last time point with a measurable concentration (AUC)last, and extrapolated to infinity (AUCinf) were lower by 45%, 34%, and 30%, respectively, compared with fed conditions, with no clinically relevant differences in COBI, FTC, or TAF exposures between fed and fasted conditions. In the bioequivalence study 90% confidence intervals of the geometric mean ratios of all main pharmacokinetic parameters were within the 80.00% to 125.00% bioequivalence limits for DRV, COBI, FTC, and TAF. No grade 3/4 adverse events (AEs), serious AEs, deaths, or discontinuations due to AEs occurred. D/C/F/TAF is bioequivalent to combined administration of the separate agents. Consistent with other (co)formulations of DRV, DRV exposure was lower in fasted than in fed conditions as evaluated when taken with food, so D/C/F/TAF should be taken with food.
Application global state monitoring in optimization of parallel event‐driven simulation
Authors: Maśko Łukasz , Tudruj Marek
Published: November 2018

The paper is concerned with discrete event‐driven simulation, which is a well‐known technique used for modeling and simulating complex parallel systems. The focus of the paper is on distributed simulation, in which multiple simulated event queues are processed in parallel according to the Time Warp approach. With this approach, parallel simulation based on event queues is allowed to progress in an optimistic way until event correlation errors appear in parallel simulation branches what results in simulation rollbacks. In the absence of synchronization between simulator parallel queues, massive processing rollbacks can strongly slow down simulation. The paper presents a distributed optimistic event‐driven simulation control based on simulator global state monitoring. A systematic control of the simulator global states prevents excessive rollbacks in the Time Warp simulation. Each simulation event queue reports its progress to a global synchronizer which monitors the global simulation state based on virtual timestamps of recently processed events. Based on the global state, the synchronizer checks the simulation progress and sends control signals which asynchronously slow down servicing too advanced queues. The paper describes the principles of the proposed approach and experimental results of its basic program implementation. Comparisons to existing parallel simulation methods are provided.
CyberGIS‐Jupyter for reproducible and scalable geospatial analytics
Authors: Yin Dandong , Liu Yan , Hu Hao , Terstriep Jeff , Hong Xingchen , Padmanabhan Anand , Wang Shaowen
Published: November 2018

The interdisciplinary field of cyberGIS (geographic information science and systems (GIS) based on advanced cyberinfrastructure) has a major focus on data‐ and computation‐intensive geospatial analytics. The rapidly growing needs across many application and science domains for such analytics based on disparate geospatial big data poses significant challenges to conventional GIS approaches. This paper describes CyberGIS‐Jupyter, an innovative cyberGIS framework for achieving data‐intensive, reproducible, and scalable geospatial analytics using Jupyter Notebook based on ROGER, the first cyberGIS supercomputer. The framework adapts the Notebook with built‐in cyberGIS capabilities to accelerate gateway application development and sharing while associated data, analytics, and workflow runtime environments are encapsulated into application packages that can be elastically reproduced through cloud‐computing approaches. As a desirable outcome, data‐intensive and scalable geospatial analytics can be efficiently developed and improved and seamlessly reproduced among multidisciplinary users in a novel cyberGIS science gateway environment.
Probing Adsorption Configurations of Small Molecules on Surfaces by Single‐Molecule Tip‐Enhanced Raman Spectroscopy
Authors: Zhang Yao , Zhang Rui , Jiang Song , Zhang Yang , Dong Zhen‐Chao
Published: November 2018

Determining the adsorption configurations of organic molecules on surfaces, especially for relatively small molecules, is a key issue for understanding the microscopic physical and chemical processes in surface science. In this work, we have applied low‐temperature ultrahigh‐vacuum tip‐enhanced Raman scattering (TERS) technique to distinguish the configurations of small 4,4′‐bipyridine (44BPY) molecules adsorbed on the Ag(111) surface. The observed Raman spectra exhibit notable differences in the spectral features which can be assigned to three different molecular orientations, each featuring a specific fingerprint pattern based on the TERS selection rule that determines the distribution of the relative intensities of different vibrational peaks. Furthermore, such a small molecule can in turn act as a local probe to provide information on the local electric field distribution at the tip apex. Our work showcases the capability of TERS technique for obtaining information on adsorption configurations of small molecules on surfaces down to the single‐molecule level, which is of fundamental importance for many applications in the fields of molecular science and surface chemistry.
Performance improvement of 60‐GHz wireless optical systems with reverse‐parallel hybrid modulation scheme
Authors: Bhatia Richa , Prakash Saurabh , Saini Ekta
Published: November 2018

This paper improves the performance of 60‐GHz wireless optical system including radio over fibre (RoF) and radio over free space optics (RoFSO), based on novel reverse‐parallel (RP) hybrid modulation scheme. This scheme combines the chromatic dispersion compensation technique of parallel modulation with energy efficiency manipulation technique of reverse modulation. Superior functioning of RoFSO is provided with reverse modulation compared with normal modulation. Comparative investigations are performed by loading 60‐GHz RF signal with 2.5 and 10‐Gbps data and modulating it with both reverse and hybrid modulators. Hybrid modulation performed better with improved BER of 10−23 at distance of 51 km for 2.5‐Gbps data compared with reverse modulation with BER of 10−7.
Harvesting effects on wild bee communities in bioenergy grasslands depend on nesting guild
Authors: Spiesman Brian J. , Bennett Ashley , Isaacs Rufus , Gratton Claudio
Published: November 2018

Conversion of annual crops to native perennial grasslands for bioenergy production may help conserve wild bees by enhancing nest and food resources. However, bee response to the disturbance of biomass harvesting may depend on their nesting location, thus their vulnerability to nest destruction, and the response of the forb community on which they forage. Moreover, because bees have long foraging ranges, effects of local harvesting may depend on the amount of natural habitat in the surrounding landscape. We performed a large‐scale one‐ and two‐year experiment in Michigan and Wisconsin, USA, respectively, to examine how grassland harvesting, landscape context, and study year affect the forb community, above‐ and belowground‐nesting bee species richness, community composition, trap nest emergence, and visitation rate. In Wisconsin, harvesting increased forb richness, cover, and evenness compared to unharvested control sites. Harvesting negatively affected aboveground‐nesting bee richness and emergence from trap nests, possibly because of nest destruction during the previous harvest. By contrast, harvesting positively affected belowground‐nesting bee richness, possibly because of the greater food resource availability and reduced thatch allowing greater access to nesting sites in the soil. Harvesting also affected bee community composition, reflecting the increase in belowground‐nesting species at harvested sites. Despite harvesting effects on forb and bee communities, there was no effect on flower visitation rate, indicating little effect on pollination function. We did not find a harvest by landscape context interaction, which, in combination with the negative harvesting effect on trap nest emergence, suggests that harvesting can affect local population growth rather than simply affecting forager aggregation in different resource environments. For bees, there was no harvest by study year interaction, indicating a consistent response over a short timescale. Similarly, in Michigan, belowground‐nesting species also responded positively to harvesting, which was more pronounced in sandier soils that are preferred for nesting. However, other components of the Michigan bee and forb communities were not significantly affected by biomass harvesting. Overall, our study demonstrates that harvesting grasslands can positively affect the ~80% of bee species that nest belowground by enhancing nest and/or forage resources, but that conserving aboveground nesters may require leaving some area unharvested.
Dissecting a potential spandrel of adaptive radiation: Body depth and pectoral fin ecomorphology coevolve in Lake Malawi cichlid fishes
Authors: Hulsey Christopher D. , Holzman Roi , Meyer Axel
Published: November 2018

The evolution of body shape reflects both the ecological factors structuring organismal diversity as well as an organism's underlying anatomy. For instance, body depth in fishes is thought to determine their susceptibility to predators, attractiveness to mates, as well as swimming performance. However, the internal anatomy influencing diversification of body depth has not been extensively examined, and changes in body depth could arise as a by‐product of functional changes in other anatomical structures. Using an improved phylogenetic hypothesis for a diverse set of Lake Malawi cichlid fishes, we tested the evolutionary association between body depth and the height of the pectoral girdle. To refine the functional importance of the observed substantial correlation, we also tested the coevolution of pectoral girdle height and pectoral fin area. The extensive coevolution of these traits suggests body depth in fishes like the Lake Malawi cichlids could diverge simply as a by‐product of being tightly linked to ecomorphological divergence in other functional morphological structures like the pectoral fins.
Carnivorous pitcher plants eat a diet of certain spiders, regardless of what's on the menu
Authors: Milne Marc A. , Waller Deborah A.
Published: November 2018

The purple pitcher plant, Sarracenia purpurea, is a low‐lying carnivorous plant that uses pitcher‐shaped leaves to catch arthropod prey for nutrition. Spiders make up a significant portion of these prey. To determine the tendency of specific spider taxa to be captured by the plant, we compared the composition (by taxonomic family) of three spider assemblages: those captured by the plant, those residing on or over the plant, and those found nearby in the local environment. Although there were some broad similarities within the three spider assemblages, significant differences existed when specific families and guilds were considered. While some families (e.g., Linyphiidae and Lycosidae) and guilds (e.g., low sheet/tangle weavers) were heavily represented in all three assemblages, other groups varied, and we found that the taxonomic makeup of victimized and resident spiders did not always reflect their environmental abundances. Moreover, spider assemblages captured by S. purpurea were extremely similar across distant locations regardless of environmental spider assemblage composition, suggesting that S. purpurea is very selective in its spider capture regimen.
Hollow Carbon@NiCo2O4 Core–Shell Microspheres for Efficient Electrocatalytic Oxygen Evolution
Authors: Wu Xiujuan , Wu Xingqiang , Lee Husileng , Ye Qilun , Wang Xiaoxiao , Zhao Yimeng , Sun Licheng
Published: November 2018

Earth‐abundant transition metal oxides are considered one of the most promising oxygen evolution reaction (OER) catalysts. However, their intrinsically low electrical conductivity inhibits the fast kinetics for OER. To overcome this drawback, hollow carbon@NiCo2O4 core–shell microspheres (C@NiCo2O4 HSs) are synthesized with enhanced electrocatalytic activity and stability toward OER. The prepared C@NiCo2O4/Ni foam delivers a current density of 10 mA cm−2 at a small overpotential of 268 mV and exhibits a low Tafel slope of 54 mV dec−1. The enhanced OER performance is attributed to the enlarged specific surface area induced by the combination effect between the 1D nanosheet structure and the 3D hollow microsphere structure, and the improved electrical conductivity is ascribed to the carbon core support.
Energy dissipation models for RC members and structures
Authors: Grammatikou Sofia , Fardis Michael N. , Biskinis Dionysis
Published: November 2018

The unloading parameters of hysteretic models for RC members are given in terms of their shear‐span‐to‐depth ratio and the viscous damping used to model other energy dissipation sources. They reflect the energy dissipation in full post‐yield load cycles in 534 tests of rectangular or circular members. Pre‐yield hysteretic energy dissipation—ignored if the model is elastic till yielding—amounts in the tests to a mean viscous damping around 8.5% and can be considered in nonlinear response‐history analysis through a new model which combines constant elastic stiffness in virgin loading with hysteretic energy dissipation both before and after yielding. Models with linear behavior till yielding and hysteretic energy dissipation only after it come closer to the results of the new model if viscous damping is 5%.
Debris‐flow volumes in northeastern Italy: Relationship with drainage area and size probability
Authors: Marchi Lorenzo , Brunetti Maria Teresa , Cavalli Marco , Crema Stefano
Published: November 2018

A dataset of 809 debris flows that occurred in 537 basins in mountainous areas of northeastern Italy between the mid‐19th century and 2015 is collected and analyzed. A remarkable increase in the number of events is observed in the last four decades and is mainly ascribed to more systematic data collection. The correlation between debris‐flow volume and drainage basin area is obtained assuming a power‐law relationship. The exponent of the power‐law curve at the 50th percentile (0.67 ± 0.02) indicates negative allometry, which means that basin area grows out of proportion to debris‐flow volume. In contrast, the exponents at the 98th and 99th percentiles are close to one, implying that debris‐flow volumes grow linearly with basin areas. The isometric relationship between the largest debris flows and the corresponding basin areas is due to the enhanced debris supply provided by the activation of widespread sediment sources, the extent of which is proportional to the basin size. The probability density function of debris‐flow volume for a subset of the collected dataset is calculated using the kernel density estimation function, which permits estimating the probability of the occurrence of debris flows that exceed a given threshold volume. The comparison with debris flows in other hydroclimatic regions shows that, although debris‐flow volumes in northeastern Italy may attain high values, they are often exceeded by debris flows that occur in seismically active regions and/or are triggered by more intense rainstorms. © 2018 John Wiley & Sons, Ltd.
Optimal routing approaches for IEEE 802.15.4 TSCH networks
Authors: Di Puglia Pugliese Luigi , Zorbas Dimitrios , Guerriero Francesca , Douligeris Christos
Published: November 2018

The IEEE 802.15.4 time‐slotted channel hopping (TSCH) is a medium access control layer protocol designed for industrial internet of things applications. The TSCH focuses on the media access control layer only, while the construction of the routes relies on network layer protocols such as the routing protocol for low‐power and lossy networks. The selection of the routes toward the sink plays a significant role in the nodes duty cycle, the delay, and the reliability of the network. In this paper, we formulate a multiobjective problem taking into account the schedule length (duty cycle/delay), the average number of hops (delay), and the cost of constructing the routes (reliability). To solve this problem, we use a scalarizing version where the objective function is defined as a convex combination of the three aforementioned parameters. Optimal computational as well as simulation results are presented. The findings of the current study can be used either as an optimal static routing solution when the link qualities are known and do not considerably change through time, or as a benchmark when designing low‐power distributed protocols for TSCH networks.
Task scheduling in cloud‐based survivability applications using swarm optimization in IoT
Authors: Al‐Turjman Fadi , Hasan Mohammed Zaki , Al‐Rizzo Hussain
Published: November 2018

Internet of Things (IoT) is dramatically growing in support of the recent revolutionary cloud‐based survivability applications. It has to meet the performance expectations for these applications in real‐time while optimizing the available cloud resources. In this paper, we propose a cooperative resource scheduling in energy‐constrained applications for a reliable and fault‐tolerant performance. We present a task scheduling algorithm based on robust canonical particle swarm optimization (CPSO) and fully informed particle swarm optimization (FIPS) algorithm to solve the problem of resource allocation in both homogeneous and heterogeneous cloud‐based IoT applications. Our objective is to satisfy the quality of service in terms of throughput and delay by performing optimal task scheduling while considering the different experienced data traffic categories. Our results show that throughput and delay can be significantly improved while using the FIPS approach in comparison to the CPSO optimization algorithm.
Fuel Cell Electrolytes of Polybenzimidazole Membranes Cross‐linked with Bis(chloromethyl) Arenes
Authors: Kirkebæk A. , Aili D. , Yue B. , Vassiliev A. , Cleemann L. N. , Jensen J. O. , Li Q.
Published: November 2018

Cross‐linking of phosphoric acid doped polybenzimidazole membranes as fuel cell electrolytes represents an attractive approach to improving the mechanical robustness at a high acid loading. Numerous cross‐linking concepts have been reported in the literature, but a deeper understanding of how the cross‐linking chemistry affects the physicochemical properties of the membrane and its fuel cell performance and durability remains to be assessed. In this work, a series of cross‐linked membranes are prepared using cross‐linking agents of different regio‐chemistry and steric nature. It is shown, that the nature of the cross‐linking agent has a large impact on the effective degree of cross‐linking, which in turn determines the acid doping characteristics and ultimately the fuel cell performance and acid retention during long‐term operation.
Hydrological transit times in nested urban and agricultural watersheds in the Greater Toronto Area, Canada
Authors: Parajulee Abha , Wania Frank , Mitchell Carl P.J.
Published: November 2018

Watershed mean transit times (MTTs) are used to characterize the hydrology of watersheds. Watershed MTTs could have important implications for water quality, as relatively long MTTs imply lengthier water retention, thereby allowing more time for pollutant transformation and more moderate release of pollutants into streams. Although estimates of MTTs are common for undisturbed watersheds, only a few studies to date have applied MTT models to urbanized watersheds. In the present study, we use δ18O to compare estimates of MTTs for paired suburban‐industrial and agricultural watersheds in Toronto, Canada. Although differences in precipitation δ18O between the two watersheds were negligible, there were significant differences in stream δ18O, suggesting differences in water transport pathways. Less damping between input precipitation δ18O and output stream δ18O in the suburban‐industrial watershed indicated a larger streamflow contribution from quick‐flow transport pathways. We applied three transit time models to quantify MTTs. Considering overall model fit, root mean square error, and uncertainty in model parameters, the exponential model performed the best of the three models. Optimized MTTs using this distribution across the suburban‐industrial subwatersheds ranged from 2.1 to 2.9 months, whereas those in the agricultural subwatersheds ranged from 2.7 to 7.5 months. The relatively small difference between urban and agricultural MTTs coincides with observations elsewhere. Model efficiencies could potentially be improved, and MTTs estimated more reliably, with a higher sampling frequency that captures a greater volume of overall discharge. Overall, this work provides a distinct first glimpse into the separation of MTTs between paired watersheds with such a large contrast in their land use.