bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: POLYSTYRENE‐BEARING CYCLOPENTADIENYL METAL CATALYSTS: COPOLYMERIZATION OF A STYRENE MONOMER CONTAINING CYCLOPENTADIENE SYNTHONS
Authors: SEKIYA A. , STILLE J. K.
Published: April 2016

Die Reaktion von Norbornenon (I) mit Styryl‐MgBr (II) liefert das Carbinol (IIIa) (syn/anti‐Gemisch) das a) in das anti‐Chlorid (IIIb) (mit HCl/HzO/EtgO oder Ac‐Cl/THF) bzw. b) in das Methoxyderivat (V) (syn/anti‐Gemisch) übergeführt wird.
ChemInform Abstract: PHOTOINDUCED OXIDATIVE CLEAVAGE OF ARYLCYCLOPROPANES IN THE PRESENCE OF ORGANIC ELECTRON ACCEPTORS
Authors: MIZUNO K. , OGAWA J. , OTSUJI Y.
Published: April 2016

Die photolytische Spaltung von Arylcyclopropanen (I) in Acetonitril in Gegenwart von nucleophilen Verbindungen (III) und Elektronen‐Akzeptoren wie (IIa) bzw. (IIb) führt in mäßigen Ausbeuten zu den Produkten (IV), (V) und (VI).
ChemInform Abstract: BENZOQUINONES AND RELATED COMPOUNDS. PART 3. PREPARATION OF 1,4‐BENZOQUINONES S BY OXIDATION OF HYDROQUINONES WITH MANGANESE DIOXIDE
Authors: BRUCE J. M. , FITZJOHN S. , PARDASANI R. T.
Published: April 2016

Anstatt mit Silberoxid lassen sich die Hydrochinone (I) in trockenem Benzol auch durch Schütteln mit MnOZ zu den Chinonen (II) oxidieren.
ChemInform Abstract: REACTIONS OF MALONANILIC ACID ETHYL ESTERS WITH HETEROCUMULENES
Authors: RUDORF W.‐D. , KOCH K. , AUGUSTIN M.
Published: April 2016

Die Malonsäureethylesteranilide (I) kondensieren mit den Halogeniden (II) und CS2 in Gegenwart von NaH zu den offenkettigen S,S‐Acetalen (III) und mit den ogw‐Dihalogeniden (IV) zu den cyclischen S,S‐Acetalen (V).
ChemInform Abstract: α‐NITROKETONES. 3. STEREOCHEMISTRY OF THE NITRATION OF 1‐ACETOXYCYCLOHEXENES: SYNTHESIS OF 2‐NITROCYCLOHEXANONES
Authors: OEZBAL H. + , ZAJAC W. W. JUN.
Published: April 2016

Aus den Cyclohexanonen (I) entstehen die Enolacetate (II) und (III), deren Nitrierung untersucht wird.
ChemInform Abstract: REACTION OF PERFLUOROISOBUTYLENE WITH AROMATIC ALDEHYDES
Authors: ZEIFMAN YU. V. , SIMONYAN L. A. , SAFRONOVA Z. V. , GAMBARYAN N. P.
Published: April 2016

Perfluor‐isobutylen (II) bildet mit p‐Dimethylaminobenzaldehyd (Ia) unter Abspaltung von Carbonylfluorid (IV) das Derivat (III).
ChemInform Abstract: STEREOCHEMISTRY OF HALOGENATION OF NITRONATE ADDUCTS FROM 4‐METHOXY‐1‐NITRO‐NAPHTHALENE AND RMGX TO 1‐HALOGENO‐2‐ALKYL‐4‐METHOXY‐1‐NITRO‐1,2‐DIHYDRONAPHTHALENES AND OF SUBSEQUENT ELIMINATION TO ALKYLHALOGENONAPHTHALENES. CRYSTAL STRUCTURE OF A TETRAHYDRONAPHTHALENONE DERIVATIVE
Authors: BARTOLI G. , BOSCO M. , FORESTI E. , PRADELLA G.
Published: April 2016

Grignardverbindungen (II) reagieren mit dem 4‐Methoxy‐1‐nitro‐naphthalin (I) zu den Nitronaten (III), die nach Hydrolyse zu (IV) mit Hypochlorit und Hypobromit zu den Halogen‐nitro‐methoxy‐dihydronaphthalinen (V) bzw. (VI) führen.
ChemInform Abstract: FACILE OXETANE FORMATION IN A RIGID BICYCLO(2.2.2)OCTANE SYSTEM
Authors: DENMARK S. E.
Published: April 2016

Aus dem Triketon (I) erhält man mit Lithiumalanat die beiden Triole (II) und (III), die mit Phenylboronsäure zu (IVa) cyclokondensiert und dann zu (IVb) silyliert werden.
ChemInform Abstract: APPLICATION OF NEW β‐LACTAM SYNTHESES TO THE PREPARATION OF (.+‐.)‐3‐AMINONOCARDICINIC ACID
Authors: WASSERMAN H. H. , HLASTA D. J. , TREMPER A. W. , WU J. S.
Published: April 2016

Cyclopropanon (II) reagiert mit dem Amin (I) zu dem Addukt (III), das mit tert.‐Butylhypochlorit zu der N‐Chlorverbindung (IV) führt.
ChemInform Abstract: SYNTHESIS OF BIOLOGICALLY ACTIVE HYDRAZONES AND SUBSTITUTED PYRAZOLES FROM .beta±beta.‐DICHLOROVINYL KETONES
Authors: MIRSKOVA A. N. , LEVKOVSKAYA G. G. , VORONKOV M. G.
Published: April 2016

Durch Umsetzung mit Semicarbaziden (II) werden aus den Alkyl‐ bzw. den Aryl‐βJS‐dichlorvinylketonen (I) bzw. (IV) Semicarbazone erhalten.
ChemInform Abstract: REACTIONS OF GUANIDINE AND UREA WITH AMINONITRILES. HETEROCYCLES. 65
Authors: WENDELIN W. , KERN W. , ZMOELNIG I. + , SCHRAMM H.‐W.
Published: April 2016

Umsetzung der Aminonitrile (I) mit Guanidin (IDliefert die Imidazolindiimine (IID [isoliert als Sulfate, im Falle von (IIId) als H2SO4‐Doppelsalz mit (II)].
ChemInform Abstract: PYRYLIUM COMPOUNDS. XVI. ISOLABLE 2‐DIALKYLAMINO‐2H‐PYRANS FROM TETRA‐ AND PENTA‐SUBSTITUTED PYRYLIUM SALTS
Authors: FISCHER G. W. , ZIMMERMANN T. , WEISSENFELS M.
Published: April 2016

2,4,6‐Triaryl‐pyryliumsalze mit geeigneten Substituenten in 3‐ bzw. 3,5‐Stellung wie (I) reagieren mit den Dialkylaminen (II) in aprotischen Lösungsmitteln zu den isolierbaren Pyranen (III).
ChemInform Abstract: SYNTHESES WITH NITRILES. PART 61. SYNTHESIS AND FLUORESCENCE OF CYANO‐SUBSTITUTED 2‐AMINOPYRIDINES
Authors: KOITZ G. , FABIAN W. , SCHMIDT H.‐W. , JUNEK H.
Published: April 2016

Nach den im einzelnen im Formelschema angegebenen Methoden werden die Titelverbindungen (III), (VI), (VIII), (X), (XI) und (XIII) dargestellt, deren Absorptions‐ und Fluoreszenzspektren untersucht werden; der Einfluß der Cyangruppen wird diskutiert.
ChemInform Abstract: REISSERT COMPOUND STUDIES. XL. THE FIRST MONOCYCLIC REISSERT COMPOUNDS
Authors: VEERARAGHAVAN S. , BHATTACHARJEE D. , POPP F. D.
Published: April 2016

Pyrimidin (I) reagiert mitTrimethylsily1cyanid (II) und Benzoylchlorid (III) in Gegenwart von Aluminiumchlorid zu den Reissert‐Verbindungen (IV).
ChemInform Abstract: THE UNUSUAL FORMATION OF PYRROLO(1,2‐A)PYRAZINES IN THE REACTION OF ALKYLPYRAZINE ANIONS WITH TRANS‐1,2‐DICHLOROETHYLENE
Authors: HOUMINER Y.
Published: April 2016

Die aus den entsprechenden Alkylpyrazinen mit Lithiumdiisopropylamid leicht zugänglichen Verbindungen (I) reagieren mit trans‐1,2‐Dichlorethylen (II) zu den Cyclisierungsprodukten (III) in mäßigen Ausbeuten.
ChemInform Abstract: 2,4‐BIS(ARYLIMINO)‐1,3,5‐TRIARYLHEXAHYDRO‐S‐TRIAZINONES
Authors: RICHTER R. , ULRICH H.
Published: April 2016

Phosgen reagiert mit den Bis‐arylirnino‐1 ,3‐diaryl‐l ,3‐diazetidinen (I) zu den Spaltprodukten (III), die mit den Aminen (IV) zu den Bis‐arylimino‐hexahydro‐s‐triazinen (V) kondensiert werden.
ChemInform Abstract: PREPARATION OF MACROCYCLIC LACTONES BY RING CLOSURE OF CESIUM CARBOXYLATES
Authors: KRUIZINGA W. H. , KELLOGG R. M.
Published: April 2016

Oxidation der cyclischen Ketone (I) mit m‐Chlorperbenzoesäure gibt die Lactone (II), die mit HBr oder HI unter Ringöffnung zu den co‐Halogenalkansäuren (III) reagieren.
ChemInform Abstract: REACTION OF DIMETHYLSILYLENE WITH ALLYLIC METHYL SULFIDES
Authors: CHIHI A. , WEBER W. P.
Published: April 2016

Das durch Photolyse von Dodekamethylcyclohexasilan erzeugte Dimethylsilylen reagiert mit dem Allylmethylsulfid (I) regiospezifisch zu dem Produkt (II).
ChemInform Abstract: HOMOLYTISCHE ADDITION VON DIALKYLPHOSPHITEN AN 1,4‐DIMETHOXY‐2‐BUTIN
Authors: BREL' A. K. , RAKHIMOV A. I. , FILIMONOVA L. M.
Published: April 2016

1,4‐Dimethoxybutin (II) reagiert mit einem großen Überschuß an Phosphiten (I) zu Phosphonaten, die in der cis‐Form (III) und der trans‐Form (IV) vorliegen.
ChemInform Abstract: RADICALS BY OXIDATION OF Λ3‐PHOSPHORIN DERIVATIVES
Authors: DIMROTH K. , HEIDE W.
Published: April 2016

Die ersten ESR‐Spektren, beobachtet bei der elektrolytischen Oxidation der trisubstituierten P‐Phosphorine (I), bei der Oxidation mit DDQ oder der mit Tetracyanethen, sind nicht, wie früher angenommen, die der K3‐Phosphorin‐Kationradikale (II).
ChemInform Abstract: A NOVEL SYNTHESIS OF 4,6‐DIMETHYL‐ AND DIPHENYL‐2,5‐DIHYDRO‐1,3,5,2‐TRIAZAPHOSPHORINES
Authors: LI V.‐SH. , CATES L. A.
Published: April 2016

Phosphorsäuremonoethylesterdichlorid (I) reagiert mit Acetamidinhydrochlorid in Gegenwart von Basen zu den Cyclokondensationsprodukten (III).
ChemInform Abstract: OXYSELENATION OF DIOLEFINS WITH PHENYL SELENOCYANATE AND COPPER(II) CHLORIDE. SYNTHESIS OF CYCLIC ETHERS
Authors: TOSHIMITSU A. , AOAI T. , UEMURA S. , OKANO M.
Published: April 2016

1,5‐Cyclooctadien (I) reagiert mit Phenylselenocyanat (II) in Gegenwart von CuCl2 in Alkoholen zu den beiden cyclischen Ethern (III) und (IV), die auch über die Cyclooctene (V) erhalten werden können.
ChemInform Abstract: RING‐SUBSTITUTED (1)TITANOCENOPHANES
Authors: KLOURAS N. , KOEPF H. +
Published: April 2016

Die Titelverbindungen (I‐IIa) und (V) können dargestellt werden durch Reaktion des Silans (I) mit den entsprechenden Nacyclopentadienylverbindungen, Metallierung der erhaltenen Derivate (II) bzw. (IV) mit Butyllithium und anschließende Umsetzung mit TiCl4 in THF.
ChemInform Abstract: PHOTOCHEMICAL REACTIONS OF TRANSITION METAL‐OLEFIN COMPLEXES. III. REACTION OF TRICARBONYL‐η‐1,3,5‐CYCLOHEPTATRIENE‐CHROMIUM(0) WITH 6‐MONO‐ AND 6‐DISUBSTITUTED FULVENES
Authors: KREITER C. G. , KURZ H.
Published: April 2016

Photochemische Reaktionen zwischen Tricarbonyl‐nl,3,5‐cycloheptatrien‐chrom(0) (I) und Fulvenen (IIa)‐(IId) führen bevorzugt zu einer Verknüpfung der beiden Ringsysteme durch eine substituierte Methylenbrücke, wobei die Komplexe (IIIa), (IIIb) und (IIIc) erhalten werden.
ChemInform Abstract: NEW LAYERED COMPOUNDS WITH TRANSITION‐METAL OXIDE LAYERS SEPARATED BY COVALENTLY BOUND ORGANIC LIGANDS. MOLYBDENUM AND TUNGSTEN TRIOXIDE‐PYRIDINE
Authors: JOHNSON J. W. , JACOBSON A. J. , RICH S. M. , BRODY J. F.
Published: April 2016

Beim Erhitzen von MoO3 mit Pyridin im Überschuß unter wasserfreien Bedingungen bildet sich mikrokristallines (Ia), dessen IR‐spektroskopische und röntgenkristallographische Charakterisierung eine neue Schichtverbindung zeigt.
ChemInform Abstract: STEROIDS. CCXLVII. SYNTHESIS OF 5,6‐CYCLOPROPANOCHOLESTANE DERIVATIVES WITH AN OXYGEN FUNCTION IN POSITION 7
Authors: KOHOUT L.
Published: April 2016

In Fortführung der Untersuchungen über die Solvolyse von Cyclosteroiden werden einige der Titelverbindungen synthetisiert.
ChemInform Abstract: AMINO ACIDS AND PEPTIDES. CLXXII. USE OF THE PHENYLACETYL GROUP FOR PROTECTION OF THE LYSINE Nε‐AMINO GROUP IN SYNTHESIS OF PEPTIDES
Authors: BRTNIK F. , BARTH T. , JOST K.
Published: April 2016

Ausgehend vom Derivat (Ib) des Ne‐geschützten Lysins (Ia) wird nach üblichen Methoden das Tripeptidamid (II) aufgebaut, das durch Kondensation mit dem (bekannten) Hydrazid (III) [ 4+ (IV)], nachfolgende Reduktion und oxidative Disulfid‐Brückenbildung das geschützte Cyclopeptid (Va) (Ausb.‐Angabe in mg) liefert; die Phenylacetylgruppe in (Va) kann unter Bildung von Desamino‐Lysin‐Vasopressin (Vb) durch Einwirkung von Penici11in‐Amidohydrolase (E93 .5.
ChemInform Abstract: BUILDING UNITS FOR OLIGOSACCHARIDES. XXX. NEW EFFECTIVE β‐GLYCOSIDE SYNTHESIS OF MANNOSE GLYCOSIDES. SYNTHESES OF MANNOSE CONTAINING OLIGOSACCHARIDES
Authors: PAULSEN H. , LOCKHOFF O.
Published: April 2016

Eine neue Methode zur selektiven Synthese von Oligosacchariden mit β‐verknüpfter Mannose‐Einheit wird entwickelt, für deren indirekte Gewinnung es bisher kein Verfahren gab.
ChemInform Abstract: PHASE TRANSFER CATALYSTS BASED ON SUCROSE ETHYLENE OXIDE ADDUCTS
Authors: GRUBER H. , GREBER G.
Published: April 2016

Saccharose (I)‐Ethylenoxid (II)‐Addukte (III) werden durch Umsetzung von (I) mit verschiedenen Mengen (II) dargestellt.
ChemInform Abstract: A STEREOCONTROLLED SYNTHESIS OF Z AND E TERMINAL DIENES FROM PINACOL E‐1‐TRIMETHYLSILYL‐1‐PROPENE‐3‐BORONATE
Authors: TSAI D. J. S. , MATTESON D. S.
Published: April 2016

Das Boronat (III) kann in der angegebenen Weise hergestellt und dann mit den Aldehyden (IV) zu den Silyl‐boronaten (Va) kondensiert werden.
ChemInform Abstract: TERNARY COMPLEXES IN SOLUTION. PART 36. STABILITY OF BINARY AND TERNARY β‐ALANINE CONTAINING DIPEPTIDE COPPER(II) COMPLEXES
Authors: SIGEL H. , PRIJS B. , MARTIN R. B.
Published: April 2016

Gleichgewichtskonstanten werden mittels potentiometrischer pH‐Messungen für die Protonierung und die Cu(II)‐Koordination von Gly‐NHQ , Gly‐gly, Gly‐β‐ala, β‐Ala‐gly, β‐Alα‐β‐ala und β‐Ala‐NH2 bestimmt.
ChemInform Abstract: ACTIVATION OF OXIDATIONS WITH OXYGEN ON METALLIC PLATINUM AS AN EXAMPLE OF THE CONVERSION OF 2‐PHENOXYETHANOLS TO PHENOXYACETIC ACIDS
Authors: FIEGE H. , WEDEMEYER K.
Published: April 2016

Zusätze von Pb‐ oder Bi‐nitrat ermöglichen bei gleichzeitiger Anwesenheit von Cd‐nitrat als Coaktivator die Oxidation von Phenoxyethanol (Ia) zur Essigsäure (IIa) an Pt‐Aktivkohle (Pt‐Gehalt 0.1%).
ChemInform Abstract: PARAMAGNETIC INTERMEDIATES IN THE THERMAL REACTIONS OF BENZO(2,1‐B;3,4‐B′)DITHIOPHENE‐4,5‐DIONE WITH SOME METAL(III) COMPOUNDS OF THE HEAVIER GROUP VA ELEMENTS
Authors: ALBERTI A. , HUDSON A. , MACCIONI A. , PODDA G. , PEDULLI G. F.
Published: April 2016

Die thermischen Reaktionen von MC13‐nPhn (M: As, Sb; n: 0‐3), AsMe,Br, SbF3, BiCl3 und BiPh3 und As(III)‐ oder Sb(III)‐enthaltenden heterocyclischen Verbindungen wie (IV) mit der Titelverbindung in Diglyme, Tetraglyme oder geschmolzenem Biphenyl als Lösungsmittel, die zu paramagnetischen Addukten führen können, werden ESR‐ spektroskopisch untersucht.
Beyond the cytoskeleton: The emerging role of organelles and membrane remodeling in the regulation of axon collateral branches
Authors: Winkle Cortney C. , Taylor Kendra L. , Dent Erik W. , Gallo Gianluca , Greif Karen F. , Gupton Stephanie L.
Published: April 2016

The generation of axon collateral branches is a fundamental aspect of the development of the nervous system and the response of axons to injury. Although much has been discovered about the signaling pathways and cytoskeletal dynamics underlying branching, additional aspects of the cell biology of axon branching have received less attention. This review summarizes recent advances in our understanding of key factors involved in axon branching. This article focuses on how cytoskeletal mechanisms, intracellular organelles, such as mitochondria and the endoplasmic reticulum, and membrane remodeling (exocytosis and endocytosis) contribute to branch initiation and formation. Together this growing literature provides valuable insight as well as a platform for continued investigation into how multiple aspects of axonal cell biology are spatially and temporally orchestrated to give rise to axon branches. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1293–1307, 2016
Colocalization of cellular nanostructure using confocal fluorescence and partial wave spectroscopy
Authors: Chandler John E. , Stypula‐Cyrus Yolanda , Almassalha Luay , Bauer Greta , Bowen Leah , Subramanian Hariharan , Szleifer Igal , Backman Vadim
Published: April 2016

A new multimodal confocal microscope has been developed, which includes a parallel Partial Wave Spectroscopic (PWS) microscopy path. This combination of modalities allows molecular‐specific sensing of nanoscale intracellular structure using fluorescent labels. Combining molecular specificity and sensitivity to nanoscale structure allows localization of nanostructural intracellular changes, which is critical for understanding the mechanisms of diseases such as cancer. To demonstrate the capabilities of this multimodal instrument, we imaged HeLa cells treated with valinomycin, a potassium ionophore that uncouples oxidative phosphorylation. Colocalization of fluorescence images of the nuclei (Hoechst 33342) and mitochondria (anti‐mitochondria conjugated to Alexa Fluor 488) with PWS measurements allowed us to detect a significant decrease in nuclear nanoscale heterogeneity (Σ), while no significant change in Σ was observed at mitochondrial sites. In addition, application of the new multimodal imaging approach was demonstrated on human buccal samples prepared using a cancer screening protocol. These images demonstrate that nanoscale intracellular structure can be studied in healthy and diseased cells at molecular‐specific sites.

magnified image
Acute dextran sulfate sodium (DSS)‐induced colitis promotes gut microbial dysbiosis in mice
Authors: Munyaka Peris Mumbi , Rabbi Mohammad Fazle , Khafipour Ehsan , Ghia Jean‐Eric
Published: April 2016

The most widely used and characterized experimental model of ulcerative colitis (UC) is the epithelial erosion, dextran sulfate sodium (DSS)‐induced colitis, which is developed by administration of DSS in drinking water. We investigated fecal and colonic mucosa microbial composition and functional changes in mice treated with DSS. C57Bl/6 mice received 5% DSS in drinking water for 5 days. Inflammation was evaluated clinically and by analysis of colonic tissue cytokine levels and C‐reactive protein (CRP) in the serum. Colonic mucosa and fecal samples were used for DNA extraction and the V4 region of bacterial 16S rRNA gene was subjected to MiSeq Illumina sequencing. Alpha‐ and beta‐diversities, and compositional differences at phylum and genus levels were determined, and bacterial functional pathways were predicted. DSS increased disease severity, serum CRP and cytokines IL‐1β and IL‐6, but decreased bacterial species richness, and shifted bacterial community composition. Bacteroides, Turicibacter, Escherichia, Clostridium, Enterobacteriaceae, Clostridiaceae, Bacteroidaceae, Bacteroidales, among other taxa were associated with DSS treatment in fecal and colonic samples. Also, DSS altered microbial functional pathways in both colonic mucosa and fecal samples. Conclusions: The development of colitis in DSS model was accompanied with reduced microbial diversity and dysbiosis of gut microbiota at lower taxonomical levels.
Low‐level laser therapy as a treatment for androgenetic alopecia
Authors: Afifi Ladan , Maranda Eric L. , Zarei Mina , Delcanto Gina M. , Falto‐Aizpurua Leyre , Kluijfhout Wouter P. , Jimenez Joaquin J.
Published: April 2016

Background and Objectives

Androgenetic alopecia (AGA) affects 50% of males by age 50 and 50% of females by age 80. Recently, the use of low‐level laser therapy (LLLT) has been proposed as a treatment for hair loss and to stimulate hair regrowth in AGA. This paper aims to review the existing research studies to determine whether LLLT is an effective therapy for AGA based on objective measurements and patient satisfaction.

Study Design

A systematic literature review was done to identify articles on Medline, Google Scholar, and Embase that were published between January 1960 and November 2015. All search hits were screened by two reviewers and examined for relevant abstracts and titles. Articles were divided based on study design and assessed for risk of bias.

Results

Eleven studies were evaluated, which investigated a total of 680 patients, consisting of 444 males and 236 females. Nine out of 11 studies assessing hair count/hair density found statistically significant improvements in both males and females following LLLT treatment. Additionally, hair thickness and tensile strength significantly improved in two out of four studies. Patient satisfaction was investigated in five studies, and was overall positive, though not as profound as the objective outcomes.

Conclusion

The majority of studies covered in this review found an overall improvement in hair regrowth, thickness, and patient satisfaction following LLLT therapy. Although we should be cautious when interpreting these findings, LLLT therapy seems to be a promising monotherapy for AGA and may serve as an effective alternative for individuals unwilling to use medical therapy or undergo surgical options. Lasers Surg. Med. 49:27–39, 2017. © 2016 Wiley Periodicals, Inc.
New Diluents for Dental Composites
Authors: Moszner Norbert , Fischer Urs Karl , Angermann Jörg
Published: April 2016

Five new urethane groups containing monomers 1–5, acetylated glycerol dimethacrylate (AGDMA), and glycerol trimethacrylate (GTMA) are synthesized as alternative diluents to triethylene glycol dimethacrylate (TEGDMA) for dental resins or composites. The synthesized monomers are characterized by means of 1H NMR, 13C NMR, and IR spectroscopy. The secondary acrylamide group containing hybrid monomers 1 and 2 are solids. However, the monomers 3–5, AGDMA and GTMA are colorless and relatively low‐viscosity liquids. They are not mutagenic in the Ames test and show a lower cytotoxicity and a lower polymerization shrinkage compared to TEGDMA. The tertiary amide group containing crosslinker 3 shows a significantly higher photopolymerization rate compared to that of TEGDMA in the presence of the monomolecular Ge‐based photoinitiator Ivocerin. The synthesized diluents are evaluated in experimental dental formulations for resins, cements, and direct filling composites using a conventional binary camphorquinone/amine photoinitiator.

image
A Multicriteria Decision‐Making Application to the Conceptual Design of Mechanical Components
Authors: Renzi Cristina , Leali Francesco
Published: April 2016

Early design is crucial for the success of the final product. In the conceptual design phase, several constraints, criteria, objectives and disciplines have to be considered. To this aim, multidisciplinary optimization has proven effective for the solution of engineering design problems, even in the industrial every‐day practice, to improve and simplify the work of designers in a successful quest of the best compromise solution. In this paper, a multicriteria decision‐making (MCDM)‐based design platform for early optimal design of industrial components is proposed. In a group decision‐making context, the selection of the most suitable component among several possible layouts is performed by means of a group Fuzzy Technique for Order of Preference by Similarity to Ideal Solution approach. Hence, a multi‐objective optimization is performed on the selected component by applying a multi‐objective particle swarm optimization for finding optimal component dimensions. An industrial case study is presented for showing the efficiency of the multicriteria decision‐making‐based design platform, regarding an innovative and low‐cost solution to increase the duration of heel tips in women's shoes. Copyright © 2016 John Wiley & Sons, Ltd.
A robust return‐map algorithm for general multisurface plasticity
Authors: Adhikary D. P. , Jayasundara C. T. , Podgorney R. K. , Wilkins A. H.
Published: April 2016

Three new contributions to the field of multisurface plasticity are presented for general situations with an arbitrary number of nonlinear yield surfaces with hardening or softening. A method for handling linearly dependent flow directions is described. A residual that can be used in a line search is defined. An algorithm that has been implemented and comprehensively tested is discussed in detail. Examples are presented to illustrate the computational cost of various components of the algorithm. The overall result is that a single Newton‐Raphson iteration of the algorithm costs between 1.5 and 2 times that of an elastic calculation. Examples also illustrate the successful convergence of the algorithm in complicated situations. For example, without using the new contributions presented here, the algorithm fails to converge for approximately 50% of the trial stresses for a common geomechanical model of sedementary rocks, while the current algorithm results in complete success. Because it involves no approximations, the algorithm is used to quantify the accuracy of an efficient, pragmatic, but approximate, algorithm used for sedimentary‐rock plasticity in a commercial software package. The main weakness of the algorithm is identified as the difficulty of correctly choosing the set of initially active constraints in the general setting. Copyright © 2016 John Wiley & Sons, Ltd.
Leisure‐time physical activity and intra‐abdominal fat in young adulthood: A monozygotic co‐twin control study
Authors: Rottensteiner Mirva , Leskinen Tuija , Järvelä‐Reijonen Elina , Väisänen Karoliina , Aaltonen Sari , Kaprio Jaakko , Kujala Urho M.
Published: April 2016

Objective

To investigate differences in abdominal fat compartments between young adult monozygotic twin pairs discordant for leisure‐time physical activity.

Methods

Ten young adult male monozygotic twin pairs (age range 32‐36 years) discordant for leisure‐time physical activity during the past 3 years were systematically selected from a population‐based Finnish twin cohort. Magnetic resonance image at the level of the L2‐L3 intervertebral disc was used to predict intra‐abdominal and subcutaneous abdominal fat masses. Dietary intake was assessed with a 4‐day food diary.

Results

Inactive twins had 31% more intra‐abdominal fat than their active co‐twins (mean difference 0.52 kg, 95% CI 0.12 to 0.91,P = 0.016), whereas the difference in subcutaneous abdominal fat was only 13% (P = 0.21) and 3% in body mass index (P = 0.28). Intraperitoneal fat mass was 41% higher among inactive twins compared to their active co‐twins (mean difference 0.41 kg, 95% CI 0.11 to 0.70,P = 0.012). Dietary intake did not differ between co‐twins.

Conclusions

A lower level of physical activity is related to greater accumulation of intra‐abdominal fat among healthy adult males in their mid‐30s. The findings highlight the importance of leisure‐time physical activity independent of genes and diet in the prevention of intra‐abdominal fat accumulation from early adulthood onward.
Perceived weight discrimination, childhood maltreatment, and weight gain in U.S. adults with overweight/obesity
Authors: Udo Tomoko , Grilo Carlos M.
Published: April 2016

Objective

Perceived weight discrimination and childhood maltreatment have been independently associated with physical and mental health issues, as well as weight gain. It is not known, however, whether childhood maltreatment modifies the relationship between perceived weight discrimination and weight changes.

Methods

This study examined the relationship between perceived weight discrimination, childhood maltreatment, and changes in body mass index (BMI) over 3 years in 21,357 men and women with overweight and obesity from Wave 1 and Wave 2 surveys of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

Results

Reporting childhood maltreatment, regardless of the specific form of maltreatment, was associated with a significantly greater likelihood of perceived weight discrimination in women. Perceived weight discrimination was associated with a significantly greater increase in BMI in both genders. Among all women with perceived weight discrimination, those who also reported having experienced childhood maltreatment had significantly less BMI increase compared to those reporting not having experienced childhood maltreatment.

Conclusions

Perceived weight discrimination may foster weight gain rather than encouraging weight loss in individuals with overweight/obesity and should be addressed in prevention efforts and clinical settings. Childhood maltreatment may perhaps sensitize individuals to subsequent stressors and increase vulnerability to perceived weight discrimination, particularly in women.
Fatty liver index is a risk determinant of incident type 2 diabetes in a metabolically healthy population with obesity
Authors: Jung Chang Hee , Kang Yu Mi , Jang Jung Eun , Hwang Jenie Yoonoo , Kim Eun Hee , Park Joong‐Yeol , Kim Hong‐Kyu , Lee Woo Je
Published: April 2016

Objective

This study investigated the effect of fatty liver disease (FLD) on the risk of incident type 2 diabetes in a population with metabolically healthy obesity (MHO).

Methods

The study population comprised 34,258 Koreans without type 2 diabetes. Participants were stratified by BMI (cutoff value, 25.0 kg/m2) and metabolic health state (using Wildman criteria). FLD was defined by the fatty liver index (FLI), a predictive algorithm to detect FLD. Subjects were classified into low and high FLI groups based on tertile.

Results

At baseline, there were significant differences in FLI between four study groups. During a median follow‐up of 36.5 months, 1.7% individuals developed type 2 diabetes. The risk of incident type 2 diabetes varied for the MHO group according to the level of FLI. The risk of type 2 diabetes in the MHO with low FLI was not significantly elevated compared with the metabolically healthy individuals without obesity (MHNO) with low FLI (multivariate‐adjusted HR, 1.19 [95% CI 0.66‐2.14]). However, the MHO with high FLI had an elevated risk of incident type 2 diabetes (multivariate‐adjusted HR, 1.99 [95% CI 1.36‐2.92]).

Conclusions

MHO subjects have a substantially higher risk of incident type 2 diabetes than MHNO subjects. The presence of FLD assessed by FLI partially explains this increased risk.
Assessing Photocatalytic Activity at the Nanoscale Using Integrated Optical and Electron Microscopy
Authors: Debroye Elke , Van Loon Jordi , Gu Xian , Franklin Thomas , Hofkens Johan , Janssen Kris P. F. , Roeffaers Maarten B. J.
Published: April 2016

An integrated optical‐electron microscope is presented that enables the in situ study of dynamic processes on photoactive materials. Here, the deposition of metallic silver nanostructures at ZnO photocatalyst particles is monitored in real time under ambient conditions by means of scanning electron microscopy. Zinc oxide crystals are immobilized on an electron transparent silicon nitride window. By passing UV light through an opposing optically transparent window, the zinc oxide is illuminated resulting in the photocatalytic formation of silver nanostructures. Both windows are part of a specially designed liquid cell filled with a dilute aqueous silver nitrate solution. Using the presented system, different electron detectors are evaluated for their ability to provide detailed images despite the interference caused by the liquid surrounding the sample. Special care has to be taken since direct silver reduction from solution induced by the electron beam interferes with the photocatalytic process. Oxygen gas, produced during the photocatalytic reaction, is also shown to complicate the imaging of the dynamic nanoscale processes in the scanning electron microscope. Nevertheless, the integrated approach allows to directly establish structure–activity relationships and to unravel optically induced processes at nanostructured materials.
Weaning nocturnal ventilation and decannulation in a pediatric ventilator care program
Authors: Liptzin Deborah R. , Connell Elisabeth A. , Marable Jennifer , Marks Jill , Thrasher Jodi , Baker Christopher D.
Published: April 2016

Introduction

Children with chronic respiratory failure and upper airway disorders may require tracheostomy placement and long‐term mechanical ventilation, yet many improve to permit ventilator weaning and decannulation.

Methods

As a quality improvement project, we conducted a chart review of patients followed by our Ventilator Care Program who underwent evaluation for weaning nocturnal ventilation (NV) and/or decannulation from 2007–2014. We collected patient demographics and characterized location, monitoring techniques, and outcomes for patients undergoing weaning NV or decannulation. We attempted to implement end tidal carbon dioxide (ETCO2) monitoring and used linear regression to compare ETCO2 with morning pCO2.

Results

Weaning NV was successful in 20/21 patients. Decannulation was successful in 18/21 attempts. Once implemented, ETCO2 was piloted and successfully performed in 12 attempts (29%). Blood testing was performed in 24/42 trials (57%). When measured, the final ETCO2 result partially correlated with morning pCO2 (R2 = 0.53, P < 0.02). Neither blood testing nor ETCO2 was performed for the four patients with unsuccessful attempts.

Conclusions

Inpatient observation for weaning NV and decannulation is safe and, in most cases, successful. With close observation, weaning NV at home may also be safe. Blood testing and ETCO2 monitoring were frequently utilized, but rarely affected decision‐making since signs of respiratory distress were observed clinically prior to testing. ETCO2 monitoring may provide reassurance without venipuncture. With our experience, we propose an algorithm for weaning NV and decannulation. Pediatr Pulmonol. 2016;51:825–829. © 2016 Wiley Periodicals, Inc.
The Politics of African Household Budget Studies in South Africa
Authors: Ross Robert
Published: April 2016

This paper traces the development of studies of African household budgets in South Africa, from the 1920s up to the 1970s, and indeed in summary form till the present. It argues that, although the genre seems to be politically neutral, and only concerned to establish “the facts,” in reality the outcome of the various researches, and certainly their presentation was dependent on the political and institutional position of the researcher, whether “liberal,” linked to commercial institutions, or as part of the apartheid state.
Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study
Authors: Price R. Jordan , Lillycrop Karen A. , Burdge Graham C.
Published: April 2016

The effect of folic acid (FA) on breast cancer (BC) risk is uncertain. We hypothesised that this uncertainty may be due, in part, to differential effects of FA between BC cells with different phenotypes. To test this we investigated the effect of treatment with FA concentrations within the range of unmetabolised FA reported in humans on the expression of the transcriptome of non-transformed (MCF10A) and cancerous (MCF7 and Hs578T) BC cells. The total number of transcripts altered was: MCF10A, seventy-five (seventy up-regulated); MCF7, twenty-four (fourteen up-regulated); and Hs578T, 328 (156 up-regulated). Only the cancer-associated geneTAGLNwas altered by FA in all three cell lines. In MCF10A and Hs578T cells, FA treatment decreased pathways associated with apoptosis, cell death and senescence, but increased those associated with cell proliferation. The folate transporters SLC19A1, SLC46A1 and FOLR1 were differentially expressed between cell lines tested. However, the level of expression was not altered by FA treatment. These findings suggest that physiological concentrations of FA can induce cell type-specific changes in gene regulation in a manner that is consistent with proliferative phenotype. This has implications for understanding the role of FA in BC risk. In addition, these findings support the suggestion that differences in gene expression induced by FA may involve differential activities of folate transporters. Together these findings indicate the need for further studies of the effect of FA on BC.
Compulsory Voting and Dissatisfaction with Democracy
Authors: Singh Shane P.
Published: April 2016

Compulsory voting is often linked to pro-democracy orientations in the public. However, there is reason to question the strength and universality of this link. Engaging research on the effects of coercion and punishment, this article argues that forced participation inflates the tendency of those with negative orientations towards democracy to see the democratic system as illegitimate, and to be dissatisfied with democracy. The study finds support for these expectations in analyses of three separate cross-national surveys and a natural experiment. Compulsory voting heightens dissatisfaction with democracy within key segments of the population.
Perilymph fistula: the patients' experience
Authors: Meldrum J A , Prinsley P R
Published: April 2016

Objective:

This study aimed to assess the experiences and outcomes of patients who underwent surgical repair of a perilymph fistula in Norfolk, UK.

Methods:

The study involved a retrospective questionnaire-based patient survey and case note review of patients who had undergone tympanotomy and perilymph fistula repair between 1998 and 2012 in two district general hospitals.

Results:

Fourteen patients underwent 20 procedures, of whom 7 completed the pre- and post-operative Vertigo Symptom Scale. In five patients, there was no obvious precipitating cause. Perilymph fistula was precipitated by noise in one patient, by a pressure-increasing event in six patients and by trauma in two patients. The Vertigo Symptom Scale scores showed a statistically significant improvement following surgical repair, from a median of 67 (out of 175) pre-operatively to 19 post-operatively.

Conclusion:

In selected patients with vertigo, perilymph fistula should be considered; surgical repair can significantly improve symptoms.
Emergency presentations of head and neck cancer: a modern perspective
Authors: Bannister M , Vallamkondu V , Ah-See K W
Published: April 2016

Background:

Head and neck cancer emergency presentations are uncommon but persistent. However, there is little published literature on this aspect of cancer and patient demographics. This study aimed to assess the incidence, patient profile, tumour site and stage of emergency cancer presentations in our region.

Method:

Retrospective review of regional cancer database over a five-year period.

Results:

Emergency presentations accounted for 7 per cent of all cases. There was no difference in patient age and risk factors between the emergency and non-emergency presentations. The emergency presentation group showed a greater proportion of female patients compared to the non-emergency presentation group (30 vs 15 per cent). In all emergency presentations, the cancer was at advanced stages. Oropharyngeal cancer was the commonest emergency presentation of cancer, but the third commonest in the non-emergency group.

Conclusion:

Emergency presentations are increasing annually. Female patients and oropharyngeal cancer showed greater representation compared to male patients and laryngeal cancer.
Hypertension-associated C825T polymorphism impairs the function of Gβ3 to target GRK2 ubiquitination
Authors: Zha Zhengyu , Han Xiao-Ran , Smith Matthew D , Lei Qun-Ying , Guan Kun-Liang , Xiong Yue
Published: April 2016

Population-based and case–control studies in different ethnicities have linked a polymorphism, C825T, in exon 10 of GNB3 gene to hypertension and several additional diseases. The 825T allele is associated with alternative splicing and results in a shortened Gβ3 protein, referred to as Gβ3s, which loses 41 amino acids encompassing one WD40 repeat domain. The mechanism of how Gβ3 C825T polymorphism is associated with hypertension has remained unclear, but an impairment of its canonical function in G-protein-coupled receptor signaling has been ruled out. Here, we report that Gβ3, like other Gβ proteins, binds to DDB1 and assembles a DDB1-CUL4A-ROC1 E3 ubiquitin ligase (CRL4AGβ3) to target GRK2 ubiquitination. The loss of the 41 amino-acid residues disrupts the Gβ3-DDB1 binding and impairs the function of Gβ3s to ubiquitinate GRK2. GRK2 ubiquitination levels were decreased and protein levels were accumulated in the blood samples of Gβ3 825T allele carriers. Deletion of Cul4a in mice resulted in systolic pressure increased and weakened heart function in male mice that can be partially rescued by the deletion of one Grk2 allele. These results reveal a mechanism explaining the link between Gβ3 C825T polymorphism and hypertension.
An inhibitor of chondroitin sulfate proteoglycan synthesis promotes central nervous system remyelination
Authors: Keough Michael B. , Rogers James A. , Zhang Ping , Jensen Samuel K. , Stephenson Erin L. , Chen Tieyu , Hurlbert Mitchel G. , Lau Lorraine W. , Rawji Khalil S. , Plemel Jason R. , Koch Marcus , Ling Chang-Chun , Yong V. Wee
Published: April 2016

Remyelination is the generation of new myelin sheaths after injury facilitated by processes of differentiating oligodendrocyte precursor cells (OPCs). Although this repair phenomenon occurs in lesions of multiple sclerosis patients, many lesions fail to completely remyelinate. A number of factors have been identified that contribute to remyelination failure, including the upregulated chondroitin sulfate proteoglycans (CSPGs) that comprise part of the astrogliotic scar. We show that in vitro, OPCs have dramatically reduced process outgrowth in the presence of CSPGs, and a medication library that includes a number of recently reported OPC differentiation drugs failed to rescue this inhibitory phenotype on CSPGs. We introduce a novel CSPG synthesis inhibitor to reduce CSPG content and find rescued process outgrowth from OPCs in vitro and accelerated remyelination following focal demyelination in mice. Preventing CSPG deposition into the lesion microenvironment may be a useful strategy to promote repair in multiple sclerosis and other neurological disorders.
Neural substrates of cognitive biases during probabilistic inference
Authors: Soltani Alireza , Khorsand Peyman , Guo Clara , Farashahi Shiva , Liu Janet
Published: April 2016

Decision making often requires simultaneously learning about and combining evidence from various sources of information. However, when making inferences from these sources, humans show systematic biases that are often attributed to heuristics or limitations in cognitive processes. Here we use a combination of experimental and modelling approaches to reveal neural substrates of probabilistic inference and corresponding biases. We find systematic deviations from normative accounts of inference when alternative options are not equally rewarding; subjects’ choice behaviour is biased towards the more rewarding option, whereas their inferences about individual cues show the opposite bias. Moreover, inference bias about combinations of cues depends on the number of cues. Using a biophysically plausible model, we link these biases to synaptic plasticity mechanisms modulated by reward expectation and attention. We demonstrate that inference relies on direct estimation of posteriors, not on combination of likelihoods and prior. Our work reveals novel mechanisms underlying cognitive biases and contributions of interactions between reward-dependent learning, decision making and attention to high-level reasoning.
All-optical design for inherently energy-conserving reversible gates and circuits
Authors: Cohen Eyal , Dolev Shlomi , Rosenblit Michael
Published: April 2016

As energy efficiency becomes a paramount issue in this day and age, reversible computing may serve as a critical step towards energy conservation in information technology. The inputs of reversible computing elements define the outputs and vice versa. Some reversible gates such as the Fredkin gate are also universal; that is, they may be used to produce any logic operation. It is possible to find physical representations for the information, so that when processed with reversible logic, the energy of the output is equal to the energy of the input. It is suggested that there may be devices that will do that without applying any additional power. Here, we present a formalism that may be used to produce any reversible logic gate. We implement this method over an optical design of the Fredkin gate, which utilizes only optical elements that inherently conserve energy.
Divergent bufavirus harboured in megabats represents a new lineage of parvoviruses
Authors: Sasaki Michihito , Gonzalez Gabriel , Wada Yuji , Setiyono Agus , Handharyani Ekowati , Rahmadani Ibenu , Taha Siswatiana , Adiani Sri , Latief Munira , Kholilullah Zainal Abidin , Subangkit Mawar , Kobayashi Shintaro , Nakamura Ichiro , Kimura Takashi , Orba Yasuko , Ito Kimihito , Sawa Hirofumi
Published: April 2016

Bufavirus is a recently recognized member of the genus Protoparvovirus in the subfamily Parvovirinae. It has been reported that human bufavirus was detected predominantly in patients with diarrhoea in several countries. However, little is known about bufavirus or its close relatives in nonhuman mammals. In this study, we performed nested-PCR screening and identified bufavirus from 12 megabats of Pteropus spp. in Indonesia. Furthermore, we determined nearly the full genome sequence of a novel megabat-borne bufavirus, tentatively named megabat bufavirus 1. Phylogenetic analyses showed that megabat bufavirus 1 clustered with known protoparvoviruses, including human bufavirus but represented a distinct lineage of bufavirus. Our analyses also inferred phylogenetic relationships among animal-borne bufaviruses recently reported by other studies. Recombination analyses suggested that the most common recent ancestor of megabat bufavirus 1 might have arisen from multiple genetic recombination events. These results characterized megabat bufavirus 1 as the first protoparvovirus discovered from megabats and indicates the high genetic divergence of bufavirus.
Exon-skipping and mRNA decay in human liver tissue: molecular consequences of pathogenic bile salt export pump mutations
Authors: Dröge Carola , Schaal Heiner , Engelmann Guido , Wenning Daniel , Häussinger Dieter , Kubitz Ralf
Published: April 2016

The bile salt export pump BSEP mediates bile formation. Over 150 BSEP mutations are associated with progressive familial intrahepatic cholestasis type 2 (PFIC-2), with few characterised specifically. We examined liver tissues from two PFIC-2 patients compound heterozygous for the splice-site mutation c.150 + 3A > C and either c.2783_2787dup5 resulting in a frameshift with a premature termination codon (child 1) or p.R832C (child 2). Splicing was analysed with a minigene system and mRNA sequencing from patients’ livers. Protein expression was shown by immunofluorescence. Using the minigene, c.150 + 3A > C causes complete skipping of exon 3. In liver tissue of child 1, c.2783_2787dup5 was found on DNA but not on mRNA level, implying nonsense-mediated mRNA decay (NMD) when c.2783_2787dup5 is present. Still, BSEP protein as well as mRNA with and without exon 3 were detectable and can be assigned to the c.150 + 3A > C allele. Correctly spliced transcripts despite c.150 + 3A > C were also confirmed in liver of child 2. In conclusion, we provide evidence (1) for effective NMD due to a BSEP frameshift mutation and (2) partial exon-skipping due to c.150 + 3A > C. The results illustrate that the extent of exon-skipping depends on the genomic and cellular context and that regulation of splicing may have therapeutic potential.
The role of fluid pressure in induced vs. triggered seismicity: insights from rock deformation experiments on carbonates
Authors: Scuderi Marco M. , Collettini Cristiano
Published: April 2016

Fluid overpressure is one of the primary mechanisms for tectonic fault slip, because fluids lubricate the fault and fluid pressure reduces the effective normal stress that holds the fault in place. However, current models of earthquake nucleation, based on rate- and state- friction laws, imply that stable sliding is favoured by the increase of pore fluid pressure. Despite this controversy, currently, there are only a few studies on the role of fluid pressure under controlled, laboratory conditions. Here, we use laboratory experiments, to show that the rate- and state- friction parameters do change with increasing fluid pressure. We tested carbonate gouges from sub hydrostatic to near lithostatic fluid pressure conditions and show that the friction rate parameter (a − b) evolves from velocity strengthening to velocity neutral behaviour. Furthermore, the critical slip distance, Dc, decreases from about 90 to 10 μm. Our data suggest that fluid overpressure plays an important role in controlling the mode of fault slip. Since fault rheology and fault stability parameters change with fluid pressure, we suggest that a comprehensive characterization of these parameters is fundamental for better assessing the role of fluid pressure in natural and human induced earthquakes.
Vascularised endosteal bone tissue in armoured sauropod dinosaurs
Authors: Chinsamy Anusuya , Cerda Ignacio , Powell Jaime
Published: April 2016

The presence of well-vascularised, endosteal bone in the medullary region of long bones of nonavian dinosaurs has been invoked as being homologous to medullary bone, a specialised bone tissue formed during ovulation in birds. However, similar bone tissues can result as a pathological response in modern birds and in nonavian dinosaurs and has also been reported in an immature nonavian dinosaur. Here we report on the occurrence of well-vascularised endosteally formed bone tissue in three skeletal elements of armoured titanosaur sauropods from the Upper Cretaceous of Argentina: i) within the medullary cavity of a metatarsal, ii) inside a pneumatic cavity of a posterior caudal vertebra, iii) in intra-trabecular spaces in an osteoderm. We show that considering the criteria of location, origin (or development) and histology, these endosteally derived tissues in the saltasaurine titanosaurs could be described as either medullary bone or pathological bone. Furthermore, we show that similar endosteally formed well-vascularised bone tissue is fairly widely distributed among nondinosaurian Archosauriformes and are not restricted to long bones, but can occur in the axial and dermal skeleton. We propose that independent evidence is required to verify whether vascularised endosteal bone tissues in extinct archosaurs are pathological or reproductive in nature.