bluuebunny/crossref_metadata_2025 huggingface dataset:
Tools of the Trade: Investigations into Design Strategies of Small Molecules to Target Components in Alzheimer's Disease
Authors: Derrick Jeffrey S. , Lim Mi Hee
Published: March 2015

The growing prevalence of Alzheimer's disease (AD) has warranted the development of effective therapeutic methods. Current available drugs for AD (i.e., acetylcholinesterase (AChE) inhibitors and N‐methyl‐D‐aspartate (NMDA) receptor antagonists) have only offered brief symptomatic relief. Considering that the numbers affected by AD are projected to substantially rise, long‐term strategies are urgently needed. The multiple series of small molecules to combat AD have been expanded, with current methods taking aim at factors, such as misfolded protein accumulation, metal ion dyshomeostasis, and oxidative stress. This concept article focuses on describing the design of compounds to target various components of AD and underlining recent advances that have been made.
Acid‐Stable Peroxoniobophosphate Clusters To Make Patterned Films
Authors: Son Jung‐Ho , Park Deok‐Hie , Keszler Douglas A. , Casey William H.
Published: March 2015

Two new peroxoniobophosphate clusters were isolated as tetramethylammonium (TMA) salts having the stoichiometries: TMA5[HNb4P2O14(O2)4]⋅9 H2O and TMA3[H7Nb6P4O24(O2)6]⋅7 H2O. The former is stable over the pH range: 3<pH<12 and the latter is stable only below pH 3. These two molecules interconvert as a function of solution pH. The [H7Nb6P4O24(O2)6]3− cluster can be used to fabricate patterned niobium phosphate films by electron‐beam lithography after solution deposition.
Enhancement of electric properties of polypyrrole by copper electrodeposition
Authors: Chikouche Imene , Sahari Ali , Zouaoui Ahmed , Tingry Sophie
Published: March 2015

Polypyrrole films (0.2–1.0 μm thick) were electrosynthetized in organic media by potentiodynamic electropolymerization on silicon surfaces. To improve the electronic conductivity of the polypyrrole films, elemental copper was electrodeposited directly on the film surface by simple electrolysis from a copper chloride bath. Copper electrodeposited onto the surface of the polypyrrole film was characterized by X‐ray diffraction and consisted only of Cufcc phase. The presence of copper on the PPy surface did not greatly affect the overall electronic conductivity of the material. However, immersion of polypyrrole films in Cu2+ solution for a period of time caused Cu2+ ions to enter the polypyrrole matrix. The reduction of the Cu2+after insertion into the polypyrrole template formed a polypyrrole/Cu composite with high electrical conductivity; this conductivity was higher for longer steeping (immersion) time. Raman spectroscopy shows much greater peak intensities when copper was present in the polypyrrole matrix. Scanning electron microscopy and cross‐sectional analysis showed clear differences in the appearance of the films with copper deposited onto the polypyrrole surface and copper inserted into the polypyrrole matrix.
Effect of liquid‐phase properties on separation efficiency in a randomly packed distillation column
Authors: Bader Andrea J. , Afacan Artin , Sharp Dave , Chuang Karl T.
Published: March 2015

The effects of the liquid properties on packing efficiency were investigated experimentally. Tests were performed in a column packed with ceramic Intalox® saddles, 7 mm in diameter. The distillation column was operated under total reflux and at atmospheric pressure (94 kPa). Surface tension positive (methanol/water, n‐heptane/toluene), surface tension negative (benzene/n‐heptane), and surface tension neutral (methanol/isopropanol and cyclohexane/n‐heptane) systems were selected to examine the wide range liquid property effects on the height of equivalent to a theoretical tray (HETP). The surface tension gradient was found to be the dominant factor affecting HETP in surface tension positive systems, but had no effect for the surface tension negative system. For the surface tension neutral system, it was found that the liquid diffusivities and viscosities had the greatest effect on HETP. The measured HETP data was also compared with tray results obtained from literature, to determine if packing and tray efficiencies are affected in a similar manner by the liquid properties. It was concluded that the surface tension gradient, liquid diffusivities, and viscosity have similar effects on the efficiency of packed and tray columns.
Bioisosteric Matrices for Ligands of Serotonin Receptors
Authors: Warszycki Dawid , Mordalski Stefan , Staroń Jakub , Bojarski Andrzej J.
Published: March 2015

The concept of bioisosteric replacement matrices is applied to explore the chemical space of serotonin receptor ligands, aiming to determine the most efficient ways of manipulating the affinity for all 5‐HT receptor subtypes. Analysis of a collection of over 1 million bioisosteres of compounds with measured activity towards serotonin receptors revealed that an average of 31 % of the ligands for each target are mutual bioisosteres. In addition, the collected dataset allowed the development of bioisosteric matrices—qualitative and quantitative descriptions of the biological effects of each predefined type of bioisosteric substitution, providing favored paths of modifying the compounds. The concept exemplified here for serotonin receptor ligands can likely be more broadly applied to other target classes, thus representing a useful guide for medicinal chemists designing novel ligands.
The Predicted Ensemble of Low‐Energy Conformations of Human Somatostatin Receptor Subtype 5 and the Binding of Antagonists
Authors: Dong Sijia S. , Abrol Ravinder , Goddard William A.
Published: March 2015

Human somatostatin receptor subtype 5 (hSSTR5) regulates cell proliferation and hormone secretion. However, the identification of effective therapeutic small‐molecule ligands is impeded because experimental structures are not available for any SSTR subtypes. Here, we predict the ensemble of low‐energy 3D structures of hSSTR5 using a modified GPCR Ensemble of Structures in Membrane BiLayer Environment (GEnSeMBLE) complete sampling computational method. We find that this conformational ensemble displays most interhelical interactions conserved in class A G protein‐coupled receptors (GPCRs) plus seven additional interactions (e.g., Y2.43–D3.49, T3.38–S4.53, K5.64–Y3.51) likely conserved among SSTRs. We then predicted the binding sites for a series of five known antagonists, leading to predicted binding energies consistent with experimental results reported in the literature. Molecular dynamics (MD) simulation of 50 ns in explicit water and lipid retained the predicted ligand‐bound structure and formed new interaction patterns (e.g. R3.50–T6.34) consistent with the inactive μ‐opioid receptor X‐ray structure. We suggest more than six mutations for experimental validation of our prediction. The final predicted receptor conformations and antagonist binding sites provide valuable insights for designing new small‐molecule drugs targeting SSTRs.
Iodide‐Free Ionic Liquid with Dual Redox Couples for Dye‐Sensitized Solar Cells with High Open‐Circuit Voltage
Authors: Li Chun‐Ting , Lee Chuan‐Pei , Lee Chi‐Ta , Li Sie‐Rong , Sun Shih‐Sheng , Ho Kuo‐Chuan
Published: March 2015

A novel ionic‐liquid mediator, 1‐butyl‐3‐{2‐oxo‐2‐[(2,2,6,6‐tetramethylpiperidin‐4‐yl)amino]ethyl}‐1H‐imidazol‐3‐ium selenocyanate (ITSeCN), has been successfully synthesized for dye‐sensitized solar cells (DSSCs). ITSeCN possesses dual redox channels, imidazolium‐functionalized 2,2,6,6‐tetramethylpiperidine N‐oxyl (TEMPO) and selenocyanate, which can serve as the cationic redox mediator and the anionic redox mediator, respectively. Therefore, ITSeCN has a favorable redox nature, which results in a more positive standard potential, larger diffusivity, and better kinetic heterogeneous rate constant than those of iodide. The DSSC with the ITSeCN electrolyte shows an efficiency of 8.38 % with a high open‐current voltage (VOC) of 854.3 mV, and this VOC value is about 150 mV higher than that for the iodide‐based DSSC. Moreover, different electrocatalytic materials were employed to trigger the redox reaction of ITSeCN. The ITSeCN‐based DSSC with the CoSe counter electrode achieved the best performance of 9.01 %, which suggested that transition‐metal compound‐type materials would be suitable for our newly synthesized ITSeCN mediator.
Bulky Monodentate Biphenylarsine Ligands: Synthesis and Evaluation of Their Structure Effects in the Palladium‐Catalyzed Heck Reaction
Authors: Quinteros Gisela J. , Uberman Paula M. , Martín Sandra E.
Published: March 2015

Biphenyl‐based arsine ligands were prepared in two‐step fashion by Pd‐catalyzed arsination and microwave‐assisted Suzuki–Miyaura coupling, providing sterically demanding arsine ligands in overall isolated yields up to 82 % as air‐stable solids. Short reaction times were achieved with the assistance of microwave irradiation in the direct and simple described protocol for the synthesis of biarylarsine ligands. The activities of the biphenyl arsine ligands were explored in Pd‐catalyzed Heck coupling. As a general trend, the ligands with “blocked” ortho‐positions on the non‐arsine‐containing ring of the biphenyl backbone performed more efficiently in the coupling reaction. This catalytic system allowed several interesting stilbenes to be obtained in very good yields.
Neurobiological and Clinical Variables Associated with Alcohol Abuse in Bulimia Nervosa
Authors: Vaz‐Leal Francisco J. , Ramos‐Fuentes María I. , Rodríguez‐Santos Laura , Flores‐Mateos Isabel S. , Franco‐Zambrano Andrés , Rojo‐Moreno Luis , Beato‐Fernández Luis
Published: March 2015

The study was aimed at analysing the reciprocal relationships of several clinical and neurobiological items in order to predict alcohol misuse in patients with bulimia nervosa (BN). Seventy BN patients and 70 healthy controls were assessed for depression, impulsivity, borderline personality traits and self‐defeating behaviours using specific scales; serum cortisol and 24‐hour urinary excretion of serotonin and 5‐hydroxiindolacetic acid were also assessed. The study confirmed the implications of these clinical factors for alcohol misuse in BN patients, but the results suggested that depressive symptoms and hypercortisolism could lie behind these relationships. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.
Prioritization of pharmaceuticals for potential environmental hazard through leveraging a large-scale mammalian pharmacological dataset
Authors: Berninger Jason P. , LaLone Carlie A. , Villeneuve Daniel L. , Ankley Gerald T.
Published: March 2015

The potential for pharmaceuticals in the environment to cause adverse ecological effects is of increasing concern. Given the thousands of active pharmaceutical ingredients (APIs) that can enter the aquatic environment through human and/or animal (e.g., livestock) waste, a current challenge in aquatic toxicology is identifying those that pose the greatest risk. Because empirical toxicity information for aquatic species is generally lacking for pharmaceuticals, an important data source for prioritization is that generated during the mammalian drug development process. Applying concepts of species read-across, mammalian pharmacokinetic data were used to systematically prioritize APIs by estimating their potential to cause adverse biological consequences to aquatic organisms, using fish as an example. Mammalian absorption, distribution, metabolism, and excretion (ADME) data (e.g., peak plasma concentration, apparent volume of distribution, clearance rate, and half-life) were collected and curated, creating the Mammalian Pharmacokinetic Prioritization For Aquatic Species Targeting (MaPPFAST) database representing 1070 APIs. From these data, a probabilistic model and scoring system were developed and evaluated. Individual APIs and therapeutic classes were ranked based on clearly defined read-across assumptions for translating mammalian-derived ADME parameters to estimate potential hazard in fish (i.e., greatest predicted hazard associated with lowest mammalian peak plasma concentrations, total clearance and highest volume of distribution, half-life). It is anticipated that the MaPPFAST database and the associated API prioritization approach will help guide research and/or inform ecological risk assessment. Environ Toxicol Chem 2016;35:1007–1020. Published 2015 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.
Hydra viridissima (green Hydra) rapidly recovers from multiple magnesium pulse exposures
Authors: Prouse Andrea E. , Hogan Alicia C. , Harford Andrew J. , van Dam Rick A. , Nugegoda Dayanthi
Published: March 2015

The time taken for organisms to recover from a pulsed toxicant exposure is an important consideration when water quality guidelines are applied to intermittent events in the environment. Organisms may appear to have recovered by standard toxicity testing methods but could carry residual toxicant or damage that may make them more sensitive to subsequent pulses. Such cumulative effects may render guidelines underprotective. The present study evaluated recovery of the freshwater cnidarian Hydra viridissima following multiple pulse exposure to magnesium (Mg). The H. viridissima were exposed to 4-h pulses of 790 mg/L and 1100 mg/L separated by 2-h, 10-h, 18-h, 24-h, 48-h, and 72-h recovery periods. Twenty-four-hour pulses of 570 mg/L, 910 mg/L, and 940 mg/L were separated by 24-h, 96-h, and 168-h recovery periods. All treatments showed similar or reduced sensitivity to the second pulse when compared with the single pulse, indicating that full recovery occurred prior to a second pulse-exposure. Five variations of equivalent time-weighted average concentrations were used to compare sensitivity of Hydra with various pulse scenarios. The sensitivity of the organisms to the multiple pulses was significantly lower than the time-weighted average continuous exposure response in 3 of the 4 scenarios tested, indicating that the Hydra benefited from interpulse recovery periods. The findings will be utilized alongside those from other species to inform the use of a site-specific, duration-based water quality guideline for Mg, and they provide an example of the use of empirical data in the regulation of toxicant pulses in the environment. Environ Toxicol Chem 2015;34:1734–1743. © 2015 Commonwealth of Australia
Cadmium sulfide quantum dots induce oxidative stress and behavioral impairments in the marine clam Scrobicularia plana
Authors: Buffet Pierre-Emmanuel , Zalouk-Vergnoux Aurore , Poirier Laurence , Lopes Christelle , Risso-de-Faverney Christine , Guibbolini Marielle , Gilliland Douglas , Perrein-Ettajani Hanane , Valsami-Jones Eugenia , Mouneyrac Catherine
Published: March 2015

Cadmium sulfide (CdS) quantum dots have a number of current applications in electronics and solar cells and significant future potential in medicine. The aim of the present study was to examine the toxic effects of CdS quantum dots on the marine clam Scrobicularia plana exposed for 14 d to these nanomaterials (10 µg Cd L–1) in natural seawater and to compare them with soluble Cd. Measurement of labile Cd released from CdS quantum dots showed that 52% of CdS quantum dots remained in the nanoparticulate form. Clams accumulated the same levels of Cd regardless of the form in which it was delivered (soluble Cd vs CdS quantum dots). However, significant changes in biochemical responses were observed in clams exposed to CdS quantum dots compared with soluble Cd. Increased activities of catalase and glutathione-S-transferase were significantly higher in clams exposed in seawater to Cd as the nanoparticulate versus the soluble form, suggesting a specific nano effect. The behavior of S. plana in sediment showed impairments of foot movements only in the case of exposure to CdS quantum dots. The results show that oxidative stress and behavior biomarkers are sensitive predictors of CdS quantum dots toxicity in S. plana. Such responses, appearing well before changes might occur at the population level, demonstrate the usefulness of this model species and type of biomarker in the assessment of nanoparticle contamination in estuarine ecosystems. Environ Toxicol Chem 2015;34:1659–1664. © 2015 SETAC
Linking the chemical speciation of cerium to its bioavailability in water for a freshwater alga
Authors: El-Akl Philippe , Smith Scott , Wilkinson Kevin J.
Published: March 2015

Over the past decade, researchers have begun to use metals of the lanthanide family for numerous applications, including liquid crystal display (LCD) screens, optical fibers, and laser technology. Unfortunately, little is presently known about their bioavailability or the mechanisms by which they might cause toxicity. The present study focuses on cerium (Ce), one of the most widely used lanthanides, and on validating the biotic ligand model as a means to predict Ce bioaccumulation. Short-term exposures to Ce were performed using the unicellular alga Chlamydomonas reinhardtii, to better relate Ce bioavailability to its chemical speciation in solution. Maximum uptake fluxes (Jmax) and affinity constants for the binding of Ce to the biological uptake sites (KS) were established at pH 5.0 and pH 7.0. An apparent affinity constant of 1.8 × 107 M–1 was observed at pH 5.0, with a larger value obtained at pH 7.0 (6 × 107 M–1), albeit under conditions where equilibrium could not be confirmed. By evaluating Ce speciation using centrifugal ultrafiltration and single-particle inductively coupled plasma spectrometry, it could be concluded that very little (∼30%) Ce was truly dissolved at pH 7.0, with the majority of the metal being present in colloidal species. Speciation was also monitored by fluorescence to evaluate Ce complexation by natural organic matter (NOM). The presence of NOM decreased Ce bioaccumulation in line with free Ce concentrations. Finally, competition with calcium for the metal uptake sites was shown to result in a decrease in Ce uptake by C. reinhardtii. Environ Toxicol Chem 2015;34:1711–1719. © 2015 SETAC
Modeling Compositional Time Series with Vector Autoregressive Models
Authors: Kynčlová Petra , Filzmoser Peter , Hron Karel
Published: March 2015

Multivariate time series describing relative contributions to a total (like proportional data) are called compositional time series. They need to be transformed first to the usual Euclidean geometry before a time series model is fitted. It is shown how an appropriate transformation can be chosen, resulting in coordinates with respect to the Aitchison geometry of compositional data. Using vector autoregressive models, the standard approach based on raw data is compared with the compositional approach based on transformed data. The results from the compositional approach are consistent with the relative nature of the observations, while the analysis of the raw data leads to several inconsistencies and artifacts. The compositional approach is extended to the case when also the total of the compositional parts is of interest. Moreover, a concise methodology for an interpretation of the coordinates in the transformed space together with the corresponding statistical inference (like hypotheses testing) is provided. Copyright © 2015 John Wiley & Sons, Ltd.
Immediate memory for “when, where and what”: Short‐delay retrieval using dynamic naturalistic material
Authors: Kwok Sze Chai , Macaluso Emiliano
Published: March 2015

We investigated the neural correlates supporting three kinds of memory judgments after very short delays using naturalistic material. In two functional magnetic resonance imaging (fMRI) experiments, subjects watched short movie clips, and after a short retention (1.5–2.5 s), made mnemonic judgments about specific aspects of the clips. In Experiment 1, subjects were presented with two scenes and required to either choose the scene that happened earlier in the clip (“scene‐chronology”), or with a correct spatial arrangement (“scene‐layout”), or that had been shown (“scene‐recognition”). To segregate activity specific to seen versus unseen stimuli, in Experiment 2 only one probe image was presented (either target or foil). Across the two experiments, we replicated three patterns underlying the three specific forms of memory judgment. The precuneus was activated during temporal‐order retrieval, the superior parietal cortex was activated bilaterally for spatial‐related configuration judgments, whereas the medial frontal cortex during scene recognition. Conjunction analyses with a previous study that used analogous retrieval tasks, but a much longer delay (>1 day), demonstrated that this dissociation pattern is independent of retention delay. We conclude that analogous brain regions mediate task‐specific retrieval across vastly different delays, consistent with the proposal of scale‐invariance in episodic memory retrieval.Hum Brain Mapp 36:2495–2513, 2015. ©2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Identification of Five New Minor Constituents from the Whole Plant of Amischotolype hispida
Authors: Chang Chun‐Wei , Chang Hsun‐Shuo , Cheng Ming‐Jen , Peng Chien‐Fang , Chen Ih‐Sheng
Published: March 2015

Bioassay‐guided fractionation of the active AcOEt‐soluble layer from the whole plant of Amischotolype hispida resulted in the isolation of four new compounds, i.e., amisbenzoic acid (1), one butenolide derivative, amisnolide (2), one chlorin analog, amisphytin (3), one lignan, amislignol (4), and one metabolite isolated for the first time from nature, (−)‐glaberide I (5), along with 20 known compounds, 6–25. Their structures were elucidated on the basis of UV, IR, 1D‐ and 2D‐NMR (1H,1H‐COSY, DEPT, HSQC, HMBC), as well as HR‐ESI‐MS, analyses. Among these isolates, palmitic acid (13) showed an antimycobacterial activity with an MIC value of 20.0 μg/ml against Mycobacterium tuberculosis H37Rv.
Synthesis of New Pyrano[2′,3′: 5,6]chromeno[4,3‐b]quinolin‐4‐ones via Aza‐DielsAlder Reaction
Authors: Kumar Bejjanki Naveen , Venkatesham Akkaladevi , Nagaiah Kommu , Babu Nanubolu Jagadeesh
Published: March 2015

New pyrano[2′,3′: 5,6]chromeno[4,3‐b]quinolin‐4‐ones have been synthesized by intramolecular aza‐DielsAlder reaction of the azadienes generated in situ from aryl amines and 8‐formyl‐7‐(prop‐2‐ynyl)2,3‐disubstituted chromones using CuFe2O4 nanoparticles as a catalyst in DMSO at 80–90° in good‐to‐excellent yields. Particularly valuable features of this methodology include simple implementation, inexpensive and reusable catalyst, and good yields. The structures were established by spectroscopic data and further confirmed by X‐ray diffraction analysis of one of the products.
A Facile Synthesis of 1‐Substituted 3‐Alkoxy‐1H‐isoindoles Based on the Reaction of 2‐(Dialkoxymethyl)phenyllithiums with Nitriles, Followed by Acid‐Catalyzed Cyclization
Authors: Kuroda Minami , Kobayashi Kazuhiro
Published: March 2015

A two‐step synthesis of 1‐substituted 3‐alkoxy‐1H‐isoindoles 4 has been developed. Thus, the reaction of 2‐(dialkoxymethyl)phenyllithium compounds, which are easily generated in situ by Br/Li exchange between 1‐bromo‐2‐(dialkoxymethyl)benzenes 1 and BuLi in THF at −78°, with nitriles afforded [2‐(dialkoxymethyl)phenyl]methanimines 2, which were treated with a catalytic amount of TsOH⋅H2O in refluxing CHCl3 to give the desired products in reasonable yields. Similarly, 3‐aryl‐1‐ethoxy‐1‐methyl‐1H‐isoindoles 7 have been prepared starting from 1‐bromo‐2‐(1,1‐diethoxyethyl)benzenes 5.
Effects of Reclaimed Water on the Growth and Fruit Quality of Cucumber
Authors: Chen Feng‐Wen , Liu Chen‐Wuing
Published: March 2015

The purpose of this study was to evaluate the feasibility of using reclaimed water for cucumber irrigation. The experiment was conducted using raw canal water, and water reclaimed from treated wastewater using a natural recycling treatment system. The raw water quality met the Irrigation Water Quality Standards of Taiwan. The water quality of reclaimed water was treated within the ranges of DO: 3.9–8.4 (mg l−1); pH: 6.5–7.8; EC: 206–587 (µs cm−1, 25 °C); SS: 0.1–11.8 (mg l−1); NH4‐N: 0–18.16 (mg l−1) and BOD: 0.1–1.8 (mg l−1). The experimental period for cucumber growth was 75 days. Rg was defined as the different multiple of plant growth and used to estimate the effects of irrigation water quality. Furthermore, yield, weight, length, and diameter of cucumbers were used to quantify the influence of irrigation water quality on cucumber quality. Result shows that Rg was within the range (1.003–1.311). The heights of cucumbers grown using reclaimed water were longer than those grown using raw water. Comparing the yield, weight, length, and diameter of cucumbers irrigated by reclaimed water (RW) and by raw water (IW), the percentages of RW/IW were respectively 154, 96, 95.5 and 101%. Based on the results, this study concludes that using reclaimed water for cucumber irrigation is feasible. Copyright © 2015 John Wiley & Sons, Ltd.
Evaluation of an intramedullary bone stabilization system using a light‐curable monomer in sheep
Authors: Zani Brett G. , Baird Rose , Stanley James R. L. , Markham Peter M. , Wilke Markus , Zeiter Stephan , Beck Aswin , Nehrbass Dirk , Kopia Gregory A. , Edelman Elazer R. , Rabiner Robert
Published: March 2015

Percutaneous intramedullary fixation may provide an ideal method for stabilization of bone fractures, while avoiding the need for large tissue dissections. Tibiae in 18 sheep were treated with an intramedullary photodynamic bone stabilization system (PBSS) that comprised a polyethylene terephthalate (Dacron) balloon filled with a monomer, cured with visible light in situ, and then harvested at 30, 90, or 180 days. In additional 40 sheep, a midshaft tibial osteotomy was performed and stabilized with external fixators or external fixators combined with the PBSS and evaluated at 8, 12, and 26 weeks. Healing and biocompatibility were evaluated by radiographic analysis, micro‐computed tomography, and histopathology. In nonfractured sheep tibiae, PBSS implants conformably filled the medullary canal, while active cortical bone remodeling and apposition of new periosteal and/or endosteal bone was observed with no significant macroscopic or microscopic observations. Fractured sheep tibiae exhibited increased bone formation inside the osteotomy gap, with no significant difference when fixation was augmented by PBSS implants. Periosteal callus size gradually decreased over time and was similar in both treatment groups. No inhibition of endosteal bone remodeling or vascularization was observed with PBSS implants. Intramedullary application of a light‐curable PBSS is a biocompatible, feasible method for fracture fixation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 291–299, 2016.
Mechanical fatigue performance of PCL‐chondroprogenitor constructs after cell culture under bioreactor mechanical stimulus
Authors: Panadero Juan Alberto , Sencadas Vitor , Silva Sonia C. M. , Ribeiro Clarisse , Correia Vitor , Gama Francisco M. , Gomez Ribelles José Luis , Lanceros‐Mendez Senentxu
Published: March 2015

In tissue engineering of cartilage, polymeric scaffolds are implanted in the damaged tissue and subjected to repeated compression loading cycles. The possibility of failure due to mechanical fatigue has not been properly addressed in these scaffolds. Nevertheless, the macroporous scaffold is susceptible to failure after repeated loading–unloading cycles. This is related to inherent discontinuities in the material due to the micropore structure of the macro‐pore walls that act as stress concentration points. In this work, chondrogenic precursor cells have been seeded in poly‐ε‐caprolactone (PCL) scaffolds with fibrin and some were submitted to free swelling culture and others to cyclic loading in a bioreactor. After cell culture, all the samples were analyzed for fatigue behavior under repeated loading–unloading cycles. Moreover, some components of the extracellular matrix (ECM) were identified. No differences were observed between samples undergoing free swelling or bioreactor loading conditions, neither respect to matrix components nor to mechanical performance to fatigue. The ECM did not achieve the desired preponderance of collagen type II over collagen type I which is considered the main characteristic of hyaline cartilage ECM. However, prediction in PCL with ECM constructs was possible up to 600 cycles, an enhanced performance when compared to previous works. PCL after cell culture presents an improved fatigue resistance, despite the fact that the measured elastic modulus at the first cycle was similar to PCL with poly(vinyl alcohol) samples. This finding suggests that fatigue analysis in tissue engineering constructs can provide additional information missed with traditional mechanical measurements. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 330–338, 2016.
Global climatology of surface water temperatures of large lakes by remote sensing
Authors: Layden Aisling , Merchant Christopher , MacCallum Stuart
Published: March 2015

Lake surface water temperatures (LSWTs) of 246 globally distributed large lakes were derived from Along‐Track Scanning Radiometers (ATSR) for the period 1991–2011. The climatological cycles of mean LSWT derived from these data quantify on a global scale the responses of large lakes' surface temperatures to the annual cycle of forcing by solar radiation and the ambient meteorological conditions. LSWT cycles reflect the twice annual peak in net solar radiation for lakes between 1°S to 12°N. For lakes without a lake‐mean seasonal ice cover, LSWT extremes exceed air temperatures by 0.5–1.7 °C for maximum and 0.7–1.9 °C for minimum temperature. The summer maximum LSWTs of lakes from 25°S to 35°N show a linear decrease with increasing altitude; −3.76 ± 0.17 °C km−1 ( = 0.95), marginally lower than the corresponding air temperature decrease with altitude −4.15 ± 0.24 °C km−1 ( = 0.95). Lake altitude of tropical lakes account for 0.78–0.83 () of the variation in the March to June LSWT–air temperature differences, with differences decreasing by 1.9 °C as the altitude increases from 500 to 1800 m above sea level (a.s.l.) We define an ‘open water phase’ as the length of time the lake‐mean LSWT remains above 4 °C. There is a strong global correlation between the start and end of the lake‐mean open water phase and the spring and fall 0 °C air temperature transition days, ( = 0.74 and 0.80, respectively), allowing for a good estimation of timing and length of the open water phase of lakes without LSWT observations. Lake depth, lake altitude and distance from coast further explain some of the inter‐lake variation in the start and end of the open water phase.
Hybrid Cross‐Linking Characteristics of Hydrogel Control Stem Cell Fate
Authors: Rajesh Krishnan G. , Cheah Calvin , Sarkar Debanjan
Published: March 2015

Controlling hydrogel structures by combination of physical and chemical cross‐links provides a novel system to regulate (stem) cell fate. In this study, we designed a polyethylene glycol (PEG)‐based hydrogel where the polymer chains contain both physical and chemical cross‐linking units in the same chain with self‐assembling L‐tyrosine‐based dipeptides and photopolymerizable polyacrylate groups, respectively. It is shown that hydrogel architectures derived from this polymer are correlated to the cross‐linking mechanisms. Combination of these cross‐links controls three‐dimensional gel architecture to regulate stem cell behavior in these hydrogels. Particularly, interaction of mesenchymal stem cells with the hydrogel enabled cellular aggregation to enhance chondrogenic differentiation as observed from the deposition of chondrogenic matrix. Increased chondrogenesis was due to enhanced cell–cell adhesion, which was mediated by gel morphology. This study shows the interplay of physical and chemical cross‐links in hydrogels to regulate stem cell function and provides a novel molecular engineering tool for controlling hydrogel properties.
Aqueous corrosion behavior of creep resistant Mg‐Al‐Ba‐Ca alloys in sodium chloride solutions
Authors: Zander D. , Zumdick N. A. , Schnatterer C. , Dieringa H.
Published: March 2015

The corrosion performance of creep resistant HPDC and PDC (permanent mould direct chill casting) Mg‐Al‐Ba‐Ca alloys was investigated in three aqueous sodium chloride solutions. These ABaX materials were compared to HPDC AZ91D and PDC AZ91D and creep resistant HPDC AE42. Electrochemical measurements and SEM/EDX analysis of original material and corroded cross‐sections were conducted, in order to draw a correlation between corrosion behavior and microstructure. The major factor determining the corrosion in ABaX alloys was found to be the shape and distribution of second phases, prompting the formation of microgalvanic corrosion instead of serving as a barrier.
Influence of environmental parameters on corrosion mechanisms of steels used in oil field
Authors: Sow L. , Idrac J. , Mora P. , Font E.
Published: March 2015

The influence of several environmental parameters on NACE SSC A tests results was analysed in this study. The effect of dissolved oxygen, pH and partial pressure of hydrogen sulfide (H2S) on corrosion and cracking susceptibility has been experimented. These experiments were done on steel wires used in oil industry. Experiments have proved that the pH value is the most influential parameter on both corrosion and cracking susceptibility of samples. H2S partial pressure also has a negative effect on cracking susceptibility. The dissolved oxygen content appeared as an incriminating factor on corrosion but can reduce the cracking susceptibility of samples.
Monitoring Combretastatin A4–induced tumor hypoxia and hemodynamic changes using endogenous MR contrast and DCE‐MRI
Authors: Colliez Florence , Fruytier Anne‐Catherine , Magat Julie , Neveu Marie‐Aline , Cani Patrice D. , Gallez Bernard , Jordan Bénédicte F.
Published: March 2015

Purpose

To benchmark MOBILE (Mapping of Oxygen By Imaging Lipid relaxation Enhancement), a recent noninvasive MR method of mapping changes in tumor hypoxia, electron paramagnetic resonance (EPR) oximetry, and dynamic contrast‐enhanced MRI (DCE‐MRI) as biomarkers of changes in tumor hemodynamics induced by the antivascular agent combretastatin A4 (CA4).

Methods

NT2 and MDA‐MB‐231 mammary tumors were implanted subcutaneously in FVB/N and nude NMRI mice. Mice received 100 mg/kg of CA4 intraperitoneally 3 hr before imaging. The MOBILE sequence (assessing R1 of lipids) and the DCE sequence (assessing Ktrans hemodynamic parameter), were assessed on different cohorts. pO2 changes were confirmed on matching tumors using EPR oximetry consecutive to the MOBILE sequence. Changes in tumor vasculature were assessed using immunohistology consecutive to DCE‐MRI studies.

Results

Administration of CA4 induced a significant decrease in lipids R1 (P = 0.0273) on pooled tumor models and a reduction in tumor pO2 measured by EPR oximetry. DCE‐MRI also exhibited a significant drop of Ktrans (P < 0.01) that was confirmed by immunohistology.

Conclusion

MOBILE was identified as a marker to follow a decrease in oxygenation induced by CA4. However, DCE‐MRI showed a higher dynamic range to follow changes in tumor hemodynamics induced by CA4. Magn Reson Med 75:866–872, 2016. © 2015 Wiley Periodicals, Inc.
Rheology and crystallization behavior of PLLA/TiO2‐g‐PDLA composites
Authors: Jing Zhanxin , Shi Xuetao , Zhang Guangcheng , Li Jiang
Published: March 2015

Poly(L‐lactide) (PLLA) composites with TiO2‐g‐poly(D‐lactide) (PDLA), which was synthesized by surface‐initiated opening ring polymerization with TiO2 as initiator and Sn(Oct)2 as catalyst, were prepared by solution casting. The synthesized TiO2‐g‐PDLA was characterized by transmission electron microscope (TEM) and dynamic laser scattering (DLS), showing larger size corresponding to that of TiO2. Fourier transform infrared spectroscopy (FT‐IR) and X‐ray photoelectron spectroscopy (XPS) measurements were further carried out and indicated that PDLA was grafted onto TiO2 through covalent bond. For PLLA/TiO2‐g‐PDLA composites, the stereocomplex crystallites were formed between PDLA grafted on the surface of TiO2 and the PLLA matrix, which was determined by FT‐IR, differential scanning calorimetry (DSC), and X‐ray diffractometer (XRD). The influence of stereocomplex crystallites on the rheological behavior of PLLA/TiO2‐g‐PDLA was investigated by rheometer, which showed greater improvement of rheological properties compared to that of PLLA/TiO2 composites especially with a percolation content of TiO2‐g‐PDLA between 3 wt%–5 wt%. The crystallization and melting behavior of PLLA/TiO2‐g‐PDLA composites were studied by DSC under different thermal treatment conditions. The formed PLA stereocomplex network acted as nucleating agents and a special interphase on the functional surface of TiO2, which resulted in imperfect PLLA crystal with lower melting temperature. When the thermal treatment was close to the melting temperature of PLA stereocomplex, the crystallinity approached to the maximum. The isothermal crystallization study by polarizing microscope (POM) indicated that stereocomplex network presented stronger nucleation capacity than TiO2‐g‐PDLA. Copyright © 2015 John Wiley & Sons, Ltd.
Noninvasive prenatal diagnosis of Huntington disease: detection of the paternally inherited expanded CAG repeat in maternal plasma
Authors: van den Oever Jessica M. E. , Bijlsma Emilia K. , Feenstra Ilse , Muntjewerff Nienke , Mathijssen Inge B. , Bakker Egbert , van Belzen Martine J. , Boon Elles M. J.
Published: March 2015

Objective

With a shift towards noninvasive testing, we have explored and validated the use of noninvasive prenatal diagnosis (NIPD) for Huntington disease (HD).

Methods

Fifteen couples have been included, assessing a total of n = 20 pregnancies. Fetal paternally inherited CAG repeat length was determined in total cell‐free DNA from maternal plasma using a direct approach by PCR and subsequent fragment analysis.

Results

All fetal HD (n = 7) and intermediate (n = 3) CAG repeats could be detected in maternal plasma. Detection of repeats in the normal range (n = 10) was successful in n = 5 cases where the paternal repeat size could be distinguished from maternal repeat patterns after fragment analysis. In all other cases (n = 5), the paternal peaks coincided with the maternal peak pattern. All NIPD results were concordant with results from routine diagnostics on fetal genomic DNA from chorionic villi.

Conclusion

In this validation study, we demonstrated that all fetuses at risk for HD could be identified noninvasively in maternal plasma. Additionally, we have confirmed results from previously described case reports that NIPD for HD can be performed using a direct approach by PCR. For future diagnostics, parental CAG profiles can be used to predict the success rate for NIPD prior to testing. © 2015 John Wiley & Sons, Ltd.
A neuroligin‐1‐derived peptide stimulates phosphorylation of the NMDA receptor NR1 subunit and rescues MK‐801‐induced decrease in long‐term potentiation and memory impairment
Authors: Korshunova Irina , Gjørlund Michelle D. , Owczarek Sylwia , Petersen Anders V. , Perrier Jean‐François , Gøtzsche Casper René , Berezin Vladimir
Published: March 2015

Neuroligins (NLs) are postsynaptic adhesion molecules, interacting with presynaptic neurexins (NXs), which determine the differential formation of excitatory (glutamatergic, NL1) and inhibitory (GABAergic, NL2) synapses. We have previously demonstrated that treatment with a NL2‐derived peptide, neurolide‐2, reduces sociability and increase animal aggression. We hypothesized that interfering with NL1 function at the excitatory synapses might regulate synaptic plasticity and learning, and counteract memory deficits induced by N‐methyl‐d‐aspartate (NMDA) receptor inhibition. First, neuronal NMDA receptor phosphorylation after treatment with NL1 or a mimetic peptide, neurolide‐1, was quantified by immunoblotting. Subsequently, we investigated effects of neurolide‐1 on long‐term potentiation (LTP) induction in hippocampal slices compromised by NMDA receptor inhibitor MK‐801. Finally, we investigated neurolide‐1 effects on short‐ and long‐term social and spatial memory in social recognition, Morris water‐maze, and Y‐maze tests. We found that subcutaneous neurolide‐1 administration, restored hippocampal LTP compromised by NMDA receptor inhibitor MK‐801. It counteracted MK‐801‐induced memory deficit in the water‐maze and Y‐maze tests after long‐term treatment (24 h and 1–2 h before the test), but not after short‐term exposure (1–2 h). Long‐term exposure to neurolide‐1 also facilitated social recognition memory. In addition, neurolide‐1‐induced phosphorylation of the NMDA receptor NR1 subunit on a site important for synaptic trafficking, potentially favoring synaptic receptor retention. Our findings emphasize the role of NL1–NMDA receptor interaction in cognition, and identify neurolide‐1, as a valuable pharmacological tool to examine the in vivo role of postsynaptic NL1 in cognitive behavior in physiological and pathological conditions.
Inhibition of the compound action potentials of frog sciatic nerves by aroma oil compounds having various chemical structures
Authors: Ohtsubo Sena , Fujita Tsugumi , Matsushita Akitomo , Kumamoto Eiichi
Published: March 2015

Plant‐derived chemicals including aroma oil compounds have an ability to inhibit nerve conduction and modulate transient receptor potential (TRP) channels. Although applying aroma oils to the skin produces a local anesthetic effect, this has not been yet examined throughly. The aim of the present study was to know how nerve conduction inhibitions by aroma oil compounds are related to their chemical structures and whether these activities are mediated by TRP activation. Compound action potentials (CAPs) were recorded from the frog sciatic nerve by using the air‐gap method. Citral (aldehyde), which activates various types of TRP channels, attenuated the peak amplitude of CAP with the half‐maximal inhibitory concentration (IC50) value of 0.46 mmol/L. Another aldehyde (citronellal), alcohol (citronellol, geraniol, (±)‐linalool, (−)‐linalool, (+)‐borneol, (−)‐borneol, α‐terpineol), ester (geranyl acetate, linalyl acetate, bornyl acetate), and oxide (rose oxide) compounds also reduced CAP peak amplitudes (IC50: 0.50, 0.35, 0.53, 1.7, 2.0, 1.5, 2.3, 2.7, 0.51, 0.71, 0.44, and 2.6 mmol/L, respectively). On the other hand, the amplitudes were reduced by a small extent by hydrocarbons (myrcene and p‐cymene) and ketone (camphor) at high concentrations (2–5 mmol/L). The activities of citral and other TRP agonists ((+)‐borneol and camphor) were resistant to TRP antagonist ruthenium red. An efficacy sequence for the CAP inhibitions was generally aldehydes ≥ esters ≥ alcohols > oxides >> hydrocarbons. The CAP inhibition by the aroma oil compound was not related to its octanol–water partition coefficient. It is suggested that aroma oil compounds inhibit nerve conduction in a manner specific to their chemical structures without TRP activation.
A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa
Authors: Kang Sang Bum , Marchelletta Ronald R. , Penrose Harrison , Docherty Michael J. , McCole Declan F.
Published: March 2015

Linaclotide, a synthetic guanylyl cyclase C (GC‐C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation‐predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC‐C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short‐circuit current (Isc). Subsequent Isc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. Isc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation.
and control design for polytopic continuous‐time Markov jump linear systems with uncertain transition rates
Authors: Morais Cecília F. , Braga Márcio F. , Oliveira Ricardo C. L. F. , Peres Pedro L. D.
Published: March 2015

This paper investigates the problems of
 and
 state feedback control design for continuous‐time Markov jump linear systems. The matrices of each operation mode are supposed to be uncertain, belonging to a polytope, and the transition rate matrix is considered partly known. By appropriately modeling all the uncertain parameters in terms of a multi‐simplex domain, new design conditions are proposed, whose main advantage with respect to the existing ones is to allow the use of polynomially parameter‐dependent Lyapunov matrices to certify the mean square closed‐loop stability. Synthesis conditions are derived in terms of matrix inequalities with a scalar parameter. The conditions, which become LMIs for fixed values of the scalar, can cope with
 and
 state feedback control in both mode‐independent and mode‐dependent cases. Using polynomial Lyapunov matrices of larger degrees and performing a search for the scalar parameter, less conservative results in terms of guaranteed costs can be obtained through LMI relaxations. Numerical examples illustrate the advantages of the proposed conditions when compared with other techniques from the literature. Copyright © 2015 John Wiley & Sons, Ltd.
An end‐to‐end alternative to TCP PEPs: Initial Spreading, a TCP fast start‐up mechanism
Authors: Sallantin Renaud , Baudoin Cédric , Chaput Emmanuel , Arnal Fabrice , Dubois Emmanuel , Beylot André‐Luc
Published: March 2015

While Transmission Control Protocol (TCP) Performance Enhancing Proxy (PEP) solutions have long been undisputed to solve the inherent satellite problems, the improvement of the regular end‐to‐end TCP congestion avoidance algorithms and the recent emphasis on the PEPs drawbacks have opened the question of the PEPs sustainability.

Nevertheless, with a vast majority of Internet connections shorter than ten segments, TCP PEPs continue to be required to counter the poor efficiency of the end‐to‐end TCP start‐up mechanisms. To reduce the PEPs dependency, designing a new fast start‐up TCP mechanism is therefore a major concern. But, while enlarging the Initial Window (IW) up to ten segments is, without any doubt, the fastest solution to deal with a short‐lived connection in an uncongested network, numerous researchers are concerned about the impact of the large initial burst on an already congested network.

Based on traffic observations and real experiments, Initial Spreading has been designed to remove those concerns whatever the load and type of networks. It offers performance similar to a large IW in uncongested network and outperforms existing end‐to‐end solutions in congested networks. In this paper, we show that Initial Spreading, taking care of the satellite specificities, is an efficient end‐to‐end alternative to the TCP PEPs. Copyright © 2015 John Wiley & Sons, Ltd.