bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: AMBIDENT ANILINE REACTIVITY IN MEISENHEIMER COMPLEX FORMATION
Authors: STRAUSS M. J. , RENFROW R. A. , BUNCEL E.
Published: May 2016

Wird das Benzofuroxan (III) mit 1 Äquivalent (Äqu.) Anilin (II) in [D6 JDMSO umgesetzt, so läßt sich die Bildung des Zwitterions (I) nachweisen; aus CH3OH fallt (I) aus.
ChemInform Abstract: ALKYLATION OF ALLYLIC DERIVATIVES. 5. LOSS OF DOUBLE‐BOND CONFIGURATION ASSOCIATED WITH α‐ALKYLATION OF ALLYLIC CARBOXYLATES WITH DIALKYLCUPRATES
Authors: GOERING H. L. , KANTNER S. S.
Published: May 2016

Aus den′ (′innamyl‐acetaten (I) entstehen wenig stereospezifisch mit Dimethyllithiumctiprat die Methylierungsprodukte (II) und (III) neben geringen Anteilen an γ‐Substitutionsprodukt (IV).
ChemInform Abstract: AZO‐ AND AZOXY COMPOUNDS. VIII. SYNTHESIS OF 1‐OXIDO‐2‐ALKOXYDIAZENEALKYLACETATES BY THE NITROSATION OF ALKYLMALONIC ESTERS
Authors: YANDOVSKII V. N. , DOSHCHECHKINA T. I. , TSELINSKII I. V. , KUZNETSOV V. S.
Published: May 2016

Nitrosierung der Alkylmalonsäurediethylester (I) durch NO in Gegenwart von NaOMe und anschließendes Aufarbeiten mit Wasser ergibt die Natriumsalze (II), deren Behandlung mit Alkylierungsreagenzien [Me,SO4, Alkyliodide (IV)] und anschließend mit Wasser die Titelverbindungen (III), (V) und (VI) liefert.
ChemInform Abstract: REACTION OF ORGANIC CARBONATES WITH AMINES. III. REACTION OF AMINES WITH ALKYLENE CARBONATES
Authors: MIKHEEV V. V. , SVETLAKOV N. V. , SYSOEV V. A. , GUMEROVA R. KH.
Published: May 2016

Die Alkylencarbonate (I1), erhalten aus den Epoxiden (I) und CO2, werden mit den Aminen (III) zu den Urethanen (IV) umgesetzt.
ChemInform Abstract: NEW REACTIONS OF 4,5‐DICHLORO‐2‐(DICHLOROMETHYLENE)‐4‐CYCLOPENTENE‐1,3‐DIONE
Authors: GUNBIN V. N. , TALZI V. P. , GUDOSHNIKOV S. K. , BARYSHEVA N. A. , MASLENNIKOV E. I.
Published: May 2016

Das Furanon (I) wird durch Reaktion mit DMF oder mit DMSO in das Furandion (II) übergeführt.
ChemInform Abstract: OPTIMIZATION OF POLYMER‐SUPPORTED OLIGOETHERS AS SOLID‐LIQUID PHASE TRANSFER CATALYSTS
Authors: HEFFERNAN J. G. , SHERRINGTON D. C.
Published: May 2016

Aus einem Chlormethyl‐Polymeren (I) erhält man mit Tetraethylenglykol neben den verzweigten Estern (II) die Monosubstitutionsprodukte (IIIa), deren Tosylatc (IIIb) mit 8‐Hydroxy‐chinolin zu (Vb) führen.
ChemInform Abstract: REDOX POTENTIALS OF 4‐ARENESULFENYLIMINO‐2,6‐DI‐TERT‐BUTYL‐1,4‐BENZOQUINONES
Authors: BURMISTROV K. S. , BELOV V. V. , BURMISTROV S. I.
Published: May 2016

Das p‐Benzochinorunonoxim (I) wird zum p‐Amirlophenolderivat ′(ll) reduziert.
ChemInform Abstract: NOVEL 1,2‐ESTER TRANSPOSITION REACTIONS
Authors: TOU J. S. , SCHLEPPNIK A. A.
Published: May 2016

Aus den Ethan‐tricarbonsäure‐Derivaten (I) entstehen nach Alkylierurlg entsprechende Substitutionsprodukte (III), die mit KII über diskutierte Zwischenstufen zu den I,2‐Ulnlagerungsproduktex1 (IV) führen.
ChemInform Abstract: A NEW ROUTE TO FUNCTIONALIZED TRANS‐HYDRINDENONES
Authors: SNIDER B. B. , KIRK T. C.
Published: May 2016

Das Keton (I), das in 3 Stufen aus llydrozimtsäure dargestellt werden kann (Ausb. ca. 40%), cyclisiert sich in Gegenwart von butyliertem Hydroxytoluol (BHT) und mehr als einem und weniger als 2 Äquiv.
ChemInform Abstract: Reaktion von 1,4‐Dihydroxyanthrachinonen mit den Anionen von CH‐Säuren.
Authors: GORELIK M. V. , MISKINA E. V.
Published: May 2016

Die Anthrachinone (I) reagieren mit den C,H‐aciden Verbindungen (II) in Gegenwart von Base unter nucleophiler Substitution des Wasserstoffatoms in Position 2 und nachfolgender Cyclisierung zu den Anthrafurandionen (III).
ChemInform Abstract: STUDIES ON ISOMERIC PYRIDYLISOXAZOLES
Authors: BELGODERE E. , BOSSIO R. , DE SIO F. , MARCACCINI S. , PEPINO R.
Published: May 2016

Die Pyridyl‐ und Thienylsubstituierten Diketone (I) reagieren mit Hydroxylumin zu Gemischen von Pyridylisoxazolen (II) und (III), deren Zusammensetzung von der Art der Substituenten abhängig ist.
ChemInform Abstract: SYNTHESIS OF SOME NEW BENZOXAZOLE, BENZOTHIAZOLE AND BENZIMIDAZOLE DERIVATIVES WITH BIOLOGICAL ACTIVITY
Authors: EL‐SHERIEF H. A. H. , MAHMOUD A. M. , ABDEL‐RAHMAN A. E. , EL‐NAGGAR G. M.
Published: May 2016

Die 2‐Mereap(obenzazole (I) werden von Chloraeetamiden (II) zu den Benzuzolylthioaeetamiden (III) alkyliert, die auch aus den Benzuzo‐ Iylthioessigsäuren (VI) und den Aminen (IV) in Gegenwart des Dihydrochinolins (V) zugänglich sind.
ChemInform Abstract: NEW POLYHETERO POLYCYCLIC RING SYSTEMS. PART XIV. SYNTHESES OF 15‐OXA‐16‐AZA AND 15,16‐BISAZA ANALOGUES OF 3‐DEOXY‐12‐THIAEQUILENIN
Authors: RAMADAS S. R. , CHENCHAIAH P. C.
Published: May 2016

Das Thiaphenanthrenon (I) kondensiert mit Dimethyloxalat (II) zum Diketoester (III), der mit Hydroxylamin (IV) zum Isoxazol (V) und mit den Hydrazinen (VI) zu den Pyrazolen (VII) cycIisiert.
ChemInform Abstract: REACTION OF PYRIDINE N‐OXIDE WITH ANILINE AND P‐TOLUENESULFONYL CHLORIDE IN AN ALKALINE MEDIUM
Authors: KURBATOV YU. V. , SOLEKHOVA M. A.
Published: May 2016

Die Titelverbindungen (I), (II) und (III) werden in basischer Lösung zu 2‐Phe‐ nyl‐tosyl‐aminopyridin (IV) umgesetzt, das in 2‐Phenylamino‐pyridin (V) übergeführt wird.
ChemInform Abstract: A CONVENIENT METHOD FOR SYNTHESIS OF NOVEL 3‐(1,3,4‐OXADIAZOL‐2‐YL)METHYLENE‐2‐OXO‐1,2,3,4‐TETRAHYDROQUINOXALINES: REGIOSELECTIVE CYCLIZATION OF 3‐ETHOXYHYDRAZONOCARBONYLMETHYLENE‐2‐OXO‐1,2,3,4‐TETRAHYDROQUINOXALINE
Authors: KURASAWA Y. , MORITAKI Y. , TAKADA A.
Published: May 2016

3‐Methcixycarbonylmethylen‐tetrahydrochinoxalinon (I) wird mit Hydrazin und anschließend Orthoestern (III) in die Derivate (IV) Limgewzmdelt, die beim Erhitzen mit DBU in n‐Butanol zu Oxadiaizol‐Derivaten (V) cyclisicren.
ChemInform Abstract: REACTIONS OF FLUORINATED NITRILES WITH SULFUR(II) CHLORIDES; CRYSTAL STRUCTURE OF 2,4,6‐TRIS(DIFLUOROSULFOXIMIDO)‐1,3,5‐TRIAZENE AT 170 K
Authors: HOEFS H.‐U. , MEWS R. , NOLTEMEYER M. , SHELDRICK G. M. , SCHMIDT M. , HENKEL G. , KREBS B.
Published: May 2016

Bei Reaktion des Nitri1s(IIIa) mit (II) ohne Lösungsmittel mit Aktivkohle als Katalysator entsteht (Ia), analog verläuft die Reaktion mit SClg zu (IVa).
ChemInform Abstract: A SYNTHESIS OF ALKYNYLAZACYCLOALKANES BY THE COUPLING REACTION OF ALKYNYLBORANES AND LACTAMS
Authors: YAMAGUCHI M. , HIRAO I.
Published: May 2016

Wie im Formelschema anhand einer allgemeinen Reaktionsfolge angegeben ist, lassen sich aus Acetylenen über die entsprechenden Borderivate mit Lactamen (III) die entsprechenden Alkinyl‐Iactame erhalten.
ChemInform Abstract: SYNTHESIS OF MACROCYCLIC LACTONES BY RING ENLARGEMENT REACTION. PRELIMINARY REPORT
Authors: KOSTOVA K. , HESSE M.
Published: May 2016

Die Ketoaldehyde (II) ergeben bei ihrer Methylierung neben dem Öl (III) bereits geringe Mengen (IVa) und 10‐16% (IVb).
ChemInform Abstract: SYNTHESIS AND REARRANGEMENT OF CYCLOADDUCTS FROM TRIMETHYLSILANECARBONITRILE OXIDE
Authors: DE SARLO F. , BRANDI A. , GOTI A. , GUARNA A. , ROVERO P.
Published: May 2016

Trimethylsilanearbonitriloxid (I) reagiert mit Olefinen (II) unter lß‐dipolzirer Addition zu Dihydroisoxazolen (III), die sehr leicht unter Ringöffntmg und hydrolytischer Abspaltung des Silylrestes gespalten werden.
ChemInform Abstract: STUDY OF THE REACTIVITY AND TAUTOMERISM OF AZOLIDINES. XLVII. ALKYLATION OF SELENAZOLIDONES
Authors: LEVSHIN I. B. , V'YUNOV K. A. , TSURKAN A. A. , KNIZHNIK A. Z. , GINAK A. I.
Published: May 2016

Die Selenazolidindione (I), die mit 69‐94% Ausb. nach Literaturverfahren erhalten werden, werden in die Kaliumderivate (II) übergeführt.
ChemInform Abstract: ISOMERIZATION OF MIXED β‐CHLOROVINYL DERIVATIVES OF MERCURY
Authors: ERDYNEEV N. S. , MOGNONOV D. M. , MARKHAEVA V. P. , OKHLOBYSTIN O. YU.
Published: May 2016

Die cis‐Chlorvinylquecksilberverbindung (I) wird beim Erwärmen teilweise isomerisiert, und das entstehende Isomerengemisch (II), das sich bei weiterem Erwärmen zersetzt, enthält 32% der trans‐Verbindung.
ChemInform Abstract: SYNTHESIS OF GERMANIUM DERIVATIVES OF URACIL AND 5‐FLUOROURACIL
Authors: TAKAKUSAKI K. , KAKIMOTO N. , TAKEUCHI Y. , TOMODA S.
Published: May 2016

Uracil (Ia) und 5‐Fluor‐uracil (Ib) werden zunächst mit Acetylchlorid in Gegenwart von Basen zu (II) acetyliert und dann mit Trichlorgerman (III) definiert in Addukte (IV) übergeführt, deren Hydrolyse zu den Germaniumsesquioxiden (V) führt.
ChemInform Abstract: SYNTHESIS, CHARACTERIZATION, AND CHEMICAL REACTIVITY OF SOLUBLE BIMETALLOMERS
Authors: DRAGO R. S. , DESMOND M. J. , CORDEN B. B. , MILLER K. A.
Published: May 2016

Durch Kondensation von S‐Heptyldithiocarbazat mit 4‐tert.‐Butyl‐ö‐formylsalicylaldehyd, dessen Synthese nach einer modifizierten Vierstufen‐Ullman /Brittner‐Methode beschrieben wird, in Ethanol/Wasser 1:1 ′wird der Ligand dargestellt, der mit den Metullacetaten in Ethanol die Bimetallomeren (Ia) ergibt.
ChemInform Abstract: A NEW TOTAL SYNTHESIS OF DL‐SIRENIN
Authors: MANDAI T. , HARA K. , KAWADA M. , NOKAMI J.
Published: May 2016

Aus dem bekannten Keton (I) entsteht das Acetoxy‐nitril (II), das mit Pd‐Katalysatoren zu (III) und (IV) umgelagert werden kann.
ChemInform Abstract: NOVEL TRANSFORMATION OF PENICILLIN INTO THE PENEM NUCLEUS: SYNTHESIS OF 2‐CARBOXYPENEM DERIVATIVE
Authors: KAMETANI T. , KANAYA N. , MOCHIZUKI T. , HONDA T.
Published: May 2016

Aus dem (rAminO‐penieillansaurederivat (I) und der Diazoverbindung (II) erhält man in Gegenwart von Rh‐Kxitalyszttoren die Kondensationsprodukte (III), die mit Triethylamin zu (IV) führen und über das Ketal (Va) in die I)eri‐ tvate (Vb) und (Vc) übergefilhrt, zu (VI) verseift und dann mit Ozon zu (VII) abgebaut werden, aus dem das Cyclisiertnngsprodukt (VIII) entsteht.
ChemInform Abstract: SYNTHESIS OF NOVEL FUSED β‐LACTAMS BY INTRAMOLECULAR 1,3‐DIPOLAR CYCLOADDITIONS. 6. PHENOXYACETAMIDO ISOAZAPENEM AND ISOAZACEPHEM CARBOXYLIC ACIDS
Authors: BRANCH C. L. , PEARSON M. J.
Published: May 2016

Aus dem β‐Lactam‐akin (Ia) erhält man bei der katalytischen Hydrierung über Pd‐Bariumsulfat das Olefin (Ib), das nach Spaltung zu (IIa) in das Azid (IIb) übergeführt und dann thermisch zu (IIIa) und (IIIb) cyclisiert wird.
Modelling and experimental study of pressure elution of high‐viscosity substances with a low‐viscosity liquid from granular bed
Authors: Błaszczyk Mariola M. , Sęk Jerzy P. , Przybysz Łukasz
Published: May 2016

The pressurized elution of oily substances with high viscosities from porous granular media is of primary importance from the point of view of enhanced oil recovery techniques and technologies. Accurate prediction of such processes can lead to their technical and financial optimization. Modelling considerations existing in the literature neglect many factors affecting elution phenomena. Additionally, extensive experimental data are not available. Other description methods are needed to enable more precise descriptions of the process.

This paper develops a theoretical model which considers the dependence of oily substance elution on many parameters characterizing porous granular beds and flowing liquids. The influence of grain size distribution in the bed was considered, as well as the finite dimensions of the real bed. The bed saturation at the beginning of the process was also included in the modelling work together with eluent flow rate and media viscosity. Theoretical considerations were verified and supported with extensive experimental measurements.
Computational comparison of regional stress and deformation characteristics in tricuspid and bicuspid aortic valve leaflets
Authors: Cao K. , Sucosky P.
Published: May 2016

The bicuspid aortic valve (BAV) is the most common congenital valvular defect and a major risk factor for secondary calcific aortic valve disease. While hemodynamics is presumed to be a potential contributor to this complication, the validation of this theory has been hampered by the limited knowledge of the mechanical stress abnormalities experienced by BAV leaflets and their dependence on the heterogeneous BAV fusion patterns. The objective of this study was to compare computationally the regional and temporal fluid wall shear stress (WSS) and structural deformation characteristics in tricuspid aortic valve (TAV), type‐0, and type‐I BAV leaflets. Arbitrary Lagrangian–Eulerian fluid‐structure interaction models were designed to simulate the flow and leaflet dynamics in idealized TAV, type‐0, and type‐I BAV geometries subjected to physiologic transvalvular pressure. The regional leaflet mechanics was quantified in terms of temporal shear magnitude (TSM), oscillatory shear index (OSI), temporal shear gradient (TSG), and stretch. The simulations identified regions of WSS overloads and increased WSS bidirectionality (174% increase in temporal shear magnitude, 0.10 increase in OSI on type‐0 leaflets) in BAV leaflets relative to TAV leaflets. BAV leaflets also experienced larger radial deformations than TAV leaflets (4% increase in type‐0 BAV leaflets). Type‐I BAV leaflets exhibited contrasted WSS environments marked by WSS overloads on the non‐coronary leaflet and sub‐physiologic WSS levels on the fused leaflet. This study provides important insights into the mechanical characteristics of BAV leaflets, which may further our understanding of the role played by hemodynamic forces in BAV disease. Copyright © 2016 John Wiley & Sons, Ltd.
Molecular and Nanoscale Sensors for Detecting Ionizing Radiation in Radiotherapy
Authors: Pushpavanam Karthik , Narayanan Eshwaran , Rege Kaushal
Published: May 2016

Ever since the discovery of radioactivity, beneficial use of ionizing radiation has been pursued for the betterment of human health. In particular, fractionated radiotherapy is commonly used in the clinic for ablation of malignant tumors. Use of higher radiation dose fractions and complex dose trajectories necessitate measurements of radiation dose delivered to the target tissue and surrounding tissues in order to ensure patient safety. Traditional dosimeters including polymer gel dosimeters, radiochromic films and metal‐oxide semiconductor field effect transistors (MOSFETs) suffer from limitations, which complicate their day‐to‐day use in the clinic. Molecular and nanoscale systems offer great potential for the development of effective sensors of ionizing radiation, which can lead to quantitative dosimeters in biological settings. This review discusses recent developments based on organic and inorganic molecular and nanoscale dosimeters including quantum dots, polymers and plasmonic nanoparticles as platforms for radiation sensing. Potential advantages and challenges of translating these technologies to clinical applications are also discussed.
Core–Shell Silicon@Mesoporous TiO2 Heterostructure: Towards Solar‐Powered Photoelectrochemical Conversion
Authors: Pal Manas , Wu Hao , Jing Yunke , Li Xiaomin , Zhu Hongwei , Wang Changyao , Wang Shuai , Al‐Enizi Abdullah M. , Deng Yonghui , Zheng Gengfeng , Zhao Dongyuan
Published: May 2016

Core–shell heterostructured nanomaterials with mesopores have enormous potential applications in diverse fields. Herein, we report a facile extended Stöber method to synthesize core–shell heterostructured semiconducting nanomaterials with mesoporosity. Silver (Ag) metal‐assisted chemically wet etched p‐type silicon nanowires (Si NWs) were used as the core, and layer‐controllable mesoporous n‐type anatase TiO2 was grown as the shell to successfully fabricate the core–shell p‐Si@mesoporous n‐TiO2 hybrid materials. Detailed characterization reveals that the TiO2 shell was composed of aggregated crystalline TiO2 nanoparticles with diameters of ≈15 nm, where the TiO2 coating thickness was tuned ≈50 nm. The interstitial pores of these nanoparticles were observed with average pore sizes of 4–8 nm. The core–shell structured p‐Si@mesoporous n‐TiO2 hybrid materials were demonstrated as photocathodes for the solar‐driven photoelectrochemical (PEC) production of H2 at the semiconductor/electrolyte interface.
Electrocardiographic Effects of a Supratherapeutic Dose of Oritavancin
Authors: Mason Jay W. , Bellibas S. Eralp , Huang Nuo‐Yu , Sanabria Carlos R. , Darpo Borje
Published: May 2016

The purpose of this study was to measure oritavancin's electrocardiographic effects at a supratherapeutic dose of 1600 mg given intravenously (IV) over 3 hours. A cohort of 150 healthy volunteers were randomized to receive placebo, oritavancin, or oral moxifloxacin 400 mg in a parallel designed thorough QT study. A supratherapeutic mean maximum oritavancin concentration (Cmax) of 232 μg/mL was achieved. There was no significant effect on baseline and placebo corrected (dd) QTcF, QRS, or heart rate; ddPR was slightly increased at most time points, with a maximum mean change of 7.7 milliseconds 1 hour after infusion. Linear PK‐PD modeling predicted a 3.2‐millisecond change in the PR interval for the Cmax (138 μg/mL) observed in pivotal phase 3 studies after 1200 mg of oritavancin. Moxifloxacin produced the expected increase in ddQTcF, validating assay sensitivity. At plasma concentrations above the clinical exposures of oritavancin, no clinically or statistically significant effect on QTcF, QRS, or heart rate was observed. The increase in PR is considered clinically insignificant, given the rapid decline in initial plasma concentration of oritavancin after infusion and the expected lower Cmax in patients. A therapeutic 1200‐mg single dose of oritavancin is not anticipated to cause any clinically significant effect on cardiac electrophysiology.
Evaluation of the Effect of Tofacitinib on the Pharmacokinetics of Oral Contraceptive Steroids in Healthy Female Volunteers
Authors: Menon Sujatha , Riese Richard , Wang Ronnie , Alvey Christine W. , Shi Haihong , Petit Wendy , Krishnaswami Sriram
Published: May 2016

Tofacitinib is an oral Janus kinase inhibitor. Tofacitinib metabolism is primarily mediated by cytochrome P450 3A4. This phase 1 randomized, open‐label, 2‐way crossover study (NCT01137708) evaluated the effect of tofacitinib 30 mg twice daily on the single‐dose pharmacokinetics of combination oral contraceptives ethinylestradiol (EE) and levonorgestrel (LN). EE and LN were administered as a single Microgynon 30® tablet (30 μg EE and 150 μg LN) to 19 healthy women. In the presence of tofacitinib, the area under the curve from time zero to infinity (AUC∞) increased by 6.6% and 0.9% for EE and LN, respectively. Maximal plasma concentrations decreased by 10.4% for EE and increased by 12.2% for LN when coadministered with tofacitinib. The 90% confidence intervals for the adjusted geometric mean ratios for AUC∞ fell within the 80%–125% region for both EE and LN. Mean half‐life was similar in the presence and absence of tofacitinib: 13.8 and 13.3 hours, respectively, for EE; 25.9 and 25.4 hours, respectively, for LN. Tofacitinib had no clinically relevant net inhibitory or inductive effect on the pharmacokinetics of EE and LN. Therefore, there is no evidence to suggest dose adjustments of oral contraceptive drugs containing EE or LN when coadministered with tofacitinib.
Clinical Experience With Desvenlafaxine in Treatment of Patients With Fibromyalgia Syndrome
Authors: Allen Rob , Sharma Uma , Barlas Suna
Published: May 2016

Two multicenter, randomized, placebo‐controlled, adaptive‐design trials of desvenlafaxine for fibromyalgia syndrome (FMS) were conducted. In study 1, male and female patients were randomized to a 27‐week treatment with placebo or desvenlafaxine 50, 100, 200, or 400 mg/d. In study 2, female patients were randomized to an 8‐week treatment with placebo, desvenlafaxine 200 mg/d, or pregabalin 450 mg/d after a placebo run‐in. The primary efficacy end point was change from baseline in numeric rating scale (NRS) pain score. Protocol‐specified interim analyses were planned after 12 (study 1) and 8 (study 2) weeks of treatment. Safety data were collected. In all, 697 patients were randomly assigned to treatment in study 1. At the interim analysis (n = 346), none of the desvenlafaxine doses met the efficacy criteria (mean [SE] advantage over placebo, –0.21 [0.36] to 0.04 [0.35]), and the study was terminated. Study 2 was stopped for business reasons before the planned interim analysis. NRS scores in week 8 were –1.98 (0.37), –1.60 (0.37), and –1.70 (0.38) for placebo (n = 26), desvenlafaxine 250 mg/d (n = 24), and pregabalin 450 mg/d (n = 21), respectively; neither active treatment differed significantly from placebo. Desvenlafaxine was generally safe and well tolerated. Efficacy of desvenlafaxine for pain associated with FMS was not demonstrated.
Wide‐band aperture array using a four‐channel manifold‐type planar multiplexer and digital 2‐D IIR filterbank
Authors: Sengupta Arindam , Madanayake Arjuna , Gómez‐García Roberto , Belostotski Leonid
Published: May 2016

Emerging wide‐band communications and spectrum‐sensing systems demand support for multiple electronically scanned beams while maintaining a frequency independent, constant far‐field beam width. Realizing existing phased‐array technology on a digital scale is computationally intensive. Moreover, digitizing wide‐band signals at Nyquist rate requires complex high‐speed analog‐to‐digital converters (ADCs), which is challenging for real developments driven by the current ADC technology. A low‐complexity alternative proposed in this paper is the use of radio‐frequency (RF) channelizers for spectrum division followed by sub‐sampling of the RF sub‐bands, which results in extensive reduction of the necessary ADC operative frequency. The RF‐channelized array signals are directionally filtered using 2‐D digital filterbanks. This mixed‐domain RF/digital aperture array allows sub‐sampling, without utilizing multi‐rate 2‐D systolic arrays, which are difficult to realize in practice. Simulated examples showing 14–19 dB of rejection of wide‐band interference and noise for a processed bandwidth of 1.6 GHz are demonstrated. The sampling rate is 400 MHz. The proposed VLSI hardware uses a single‐phase clock signal of 400 MHz. Prototype hardware realizations and measurement using 65‐nm Xilinx field‐programmable gate arrays, as well as Cadence RTL synthesis results including gate counts, area‐time complexity, and dynamic power consumption for a 45‐nm CMOS circuit operating at BDC = 1.1 V, are presented. Copyright © 2016 John Wiley & Sons, Ltd.
Maternal effects as drivers of sibling competition in a parent–offspring conflict context? An experimental test
Authors: Merkling Thomas , Perrot Charlotte , Helfenstein Fabrice , Ferdy Jean‐Baptiste , Gaillard Laurent , Lefol Emilie , Voisin Emmanuelle , Hatch Scott A. , Danchin Etienne , Blanchard Pierrick
Published: May 2016

Maternal effects occur when the mother's phenotype influences her offspring's phenotype. In birds, differential allocation in egg yolk components can allow mothers to compensate for the competitive disadvantage of junior chicks. We hypothesize that the parent–older chick conflict peaks at intermediate conditions: parents benefit from the younger chick(s) survival, but its death benefits the older chick in terms of growth and survival. We thus expect maternal compensation to follow a bell‐shaped pattern in relation to environmental conditions. We studied a black‐legged kittiwake (Rissa tridactyla) population where previous results revealed increased allocation of yolk testosterone in younger as compared to older chicks in intermediate conditions, in line with our theoretical framework. We therefore predicted a maternally induced increase in aggressiveness, growth, and survival for younger chicks born in intermediate environmental conditions. Controlling for parental effects and chick sex, we manipulated food availability before egg laying to create a situation with intermediate (Unfed group) and good (Fed group) environmental conditions. Within each feeding treatment, we further created experimental broods where the natural hatching order was reversed to maximize our chances to observe an effect of feeding treatment on the younger chicks' aggressiveness. As predicted, we found that chick aggressiveness was higher in younger chicks born from the Unfed group (i.e., in intermediate environmental conditions), but only when they were put in a senior position, in reversed broods. Predictions on growth and survival were not confirmed. Mothers thus seem to favor the competitiveness of their younger chick in intermediate conditions via egg yolk components, but our study also suggests that hatching asynchrony need to be small for maternal compensation to be efficient. We emphasize the need for further studies investigating other chick behaviors (e.g., begging) and focusing on the relative role of different yolk components in shaping parent–offspring conflict over sibling competition.
An Oxidation–Amidation Approach for the Synthesis of Glycuronamides
Authors: Lin Sicheng , Ashmus Roger A. , Lowary Todd L.
Published: May 2016

A route for the synthesis of glycuronamides via the intermediacy of 6‐S‐tolyl‐substituted glycosides and uronic acid thioesters, is reported. The route, which is compatible with a variety of carbohydrate residues and protecting groups, was used to synthesize the repeating unit of the E. coli K54 capsular polysaccharide.
Excitonic Coupling in Acyclic and Cyclic Dithioaryl‐Linked BODIPY DYEmers
Authors: Ahrens Johannes , Scheja Anne , Wicht Richard , Bröring Martin
Published: May 2016

BODIPY DYEmers with dithioaryl bridges have been prepared by nucleophilic substitution reactions of α‐brominated BODIPYs. The optical properties of these compounds can be predicted by the Kashas exciton coupling model up to a critical interchromophore distance. The first macrocyclic derivative with stacked subchromophores has been obtained and proves the suitability of the Kasha model for predicting H‐type behavior from the molecular structures of this type of DYEmer.
Far‐red dependent changes in the chemical composition of Spirulina platensis
Authors: Kula Monika , Rys Magdalena , Saja Diana , Tys Jerzy , Skoczowski Andrzej
Published: May 2016

The influence of far‐red light (FRL) was studied on the chemical composition of Spirulina platensis biomass. The following light compositions were used during the culture white light, blue‐red LED light (BRL) and BRL supplemented with FRL (BRFRL). Chlorophyll and phenol contents were measured by spectrophotometric methods, whereas presence of carotenoids, lipids, and phycobiliproteins were estimated by Fourier‐transform Raman spectrometry. Additionally, phenol content was investigated by fluorescence intensity of algae culture in the range of 430–650 nm. The content of chlorophyll and phenols in algae cells depended on the spectral composition of light and was the highest under BRL (16.7 ± 0.5 and 9.1 ± 0.6, respectively). It was shown that there is a positive linear correlation (R = 0.902 at p < 0.0000001) between the ratio of relative fluorescence intensity of S. platensis suspensions at 450 nm to the suspensions at 540 nm (F450/F540) and the content of phenolic compounds in the biomass. Changes in the F450/F540 ratio can explain approximately 80% changes of phenol contents in algae cells. Spirulina platensis Raman spectra demonstrated that the biomass of algae growing under white light and BRL had a significantly higher intensity of phycobiliprotein bands than the algae growing under BRFRL.
Nanostructured Particles for Controlled Polymer Release in Enhanced Oil Recovery
Authors: Tamsilian Yousef , S. A. Ahmad Ramazani , Shaban Masoom , Ayatollahi Shahab , de la Cal Jose C. , Sheng James J. , Tomovska Radmila
Published: May 2016

With the decline in oil discoveries over recent decades, it is believed that enhanced oil recovery (EOR) technologies will play a key role to meet energy demand in the coming years. Polymer flooding is used commonly worldwide as an EOR process. In this work, we propose the synthesis of protected polyacrylamide (PAM) nanoparticles (PPNs) with a hydrophobic polystyrene (PSt) shell by one‐pot two‐step inverse emulsion polymerization, in which the PSt shell was created by surface polymerization. The shell protects the active PAM chains from premature degradation caused by the harsh environment in the reservoirs, controls the release of the chains as rheological modifiers, and additionally, it provides the chains with prolonged stability. The time‐dependent release of the PPNs promotes the effectiveness of the PPNs as viscosity modifiers, as the maximum viscosity enhancement is achieved at longer residence times in the reservoirs. This can be up to 30 days, and the released polymer maintained its activity. Under conditions of high salinity (total dissolved solids=178 082 mg L−1), temperatures up to 90 °C, and shear rates up to 1000 s−1, PPNs have shown superior properties, such as elastic modulus, shear rate behavior, viscosity loss, and sand adsorption over PAM, whereas the areal sweep efficiency of PPNs is similar to that of PAM and higher than that of conventional water flooding. All of this makes PPNs promising candidates for polymer‐enhanced oil recovery.
Simulating the thermal response of the flame manikin with different materials exposed to flash fire by CFD
Authors: Tian Miao , Li Jun
Published: May 2016

To investigate the differences of thermal response between heat flux sensors and human skin on the flame manikin, a three‐dimensional heat transfer model was developed and validated by the flame manikin system. The initial temperature of the model with sensor material was set to 300 K, and the model with skin material was set as the real condition. Simulated results validated the effectiveness of heat flux measured by the sensor. The incident heat flux through the measured surface was influenced by the different emissivity of the human skin and experimental sensors. Significant difference was found for the temperature response of these two kinds of materials within 4‐s fire exposure. The heat flux measured by sensor or the simulated results with actual human skin parameters could be used as the input boundary condition of the skin heat transfer model for Henriques's skin burn prediction. It is necessary to study the actual skin thermal response by experiments, where the 3D model established in this study could be used as the supplementary means for skin simulant sensor development. These findings will also be adopted in our following study of skin burn prediction module in the 3D full‐scale simulation platform. Copyright © 2016 John Wiley & Sons, Ltd.
Thermal and mechanical transient behaviour of steel doors installed in non‐load‐bearing partition wall assemblies during exposure to the standard fire test
Authors: Nassif Ayman Y. , Yoshitake Isamu , Vimonsatit Vanissorn
Published: May 2016

In this paper, the authors present experimental results and observations of four full‐scale standard fire tests on single‐leaf steel doors and steel frames installed in 3 × 3 m non‐load‐bearing partition walls. Three full‐scale fire tests were performed on steel doors installed in lightweight partition walls constructed by using steel C‐section studs with gypsum boards fixed on both sides. Two lightweight walls incorporated Rockwool cavity insulation, while the third lightweight wall was constructed without cavity insulation. The fourth fire test involved a steel door installed in a masonry partition wall. While the steel door leaf and door frames were identical in all four full‐scale tests, only the steel door installed in the masonry wall achieved the desired fire resistance rating of 30 min. The integrity criterion for fire resistance was determined for the scenario when the door opened away from the furnace. The duration of fire resistance according to the integrity criterion was found to be 38, 25 and 19 min for the same door when installed in masonry wall, uninsulated lightweight wall and insulated lightweight wall respectively. For the thermal insulation criterion of fire resistance, the scenario of the door opening into the fire was found to be the most onerous. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Thermal analysis of high‐performance mortar containing burnt clay shale as a partial portland cement replacement in the temperature range up to 1000 °C
Authors: Trník Anton , Scheinherrová Lenka , Kulovaná Tereza , Reiterman Pavel , Vejmelková Eva , Černý Robert
Published: May 2016

Clay shale is a specific type of material that contains a large amount of kaolinite. Burnt clay shale belongs to a large group of pozzolans, and its pozzolanic properties are activated after burning at temperatures similar to those when kaolinite is transformed into metakaolin. In this study, fine powder of burnt clay shale was used for the design of a high‐performance mortar as a partial replacement for portland cement up to 60 wt.%. The prepared specimens were subjected to a thermal analysis by using differential scanning calorimetry, thermogravimetry, and thermodilatometry. The investigation was performed in the temperature range 25–1000 °C. The basic physical and mechanical properties were studied as well. It was demonstrated that it is possible to design and produce a high‐performance mortar containing fine burnt clay shale powder and that an appropriate amount of this replacement is up to 20 wt.%. Copyright © 2016 John Wiley & Sons, Ltd.
Microbial associations with macrobiota in coastal ecosystems: patterns and implications for nitrogen cycling
Authors: Moulton Orissa M , Altabet Mark A , Beman J Michael , Deegan Linda A , Lloret Javier , Lyons Meaghan K , Nelson James A , Pfister Catherine A
Published: May 2016

In addition to their important effects on nitrogen (N) cycling via excretion and assimilation (by macrofauna and macroflora, respectively), many macrobiota also host or facilitate microbial taxa responsible for N transformations. Interest in this topic is expanding, especially as it applies to coastal marine systems where N is a limiting nutrient. Our understanding of the diversity of microbes associated with coastal marine macrofauna (invertebrate and vertebrate animals) and macrophytes (seaweeds and marine plants) is improving, and recent studies indicate that the collection of microbes living in direct association with macrobiota (the microbiome) may directly contribute to N cycling. Here, we review the roles that macrobiota play in coastal N cycling, review current knowledge of macrobial–microbial associations in terms of N processing, and suggest implications for coastal ecosystem function as animals are harvested and as foundational habitat is lost or degraded. Given the biodiversity of microbial associates of macrobiota, we advocate for more research into the functional consequences of these associations for the coastal N cycle.
A Matter of Taste
Authors: Unterstell Rembert
Published: May 2016

Biochemist Wolfgang Meyerhof studies the basic mechanisms of the long‐neglected sense of taste. He also seeks to understand the relationship between taste and nutrition. We spoke to him about the world of bitter receptors, eating the abdomens of honeybees for sweetness, and taste preferences and aversions.
Feasibility of the AML profiler (Skyline™ Array) for patient risk stratification in a multicentre trial: a preliminary comparison with the conventional approach
Authors: Nomdedéu Josep F. , Puigdecanet Eulalia , Bussaglia Elena , Hernández Juan José , Carricondo Maite , Estivill Camino , Martí‐Tutusaus Josep Maria , Tormo Mar , Zamora Lurdes , Serrano Elena , Perea Granada , de Llano Maria Paz Queipo , García Antoni , Sánchez‐Ortega Isabel , Ribera Josep Maria , Nonell Lara , Aventin Anna , Solé Francesc , Brunet Maria Salut , Sierra Jorge
Published: May 2016

Deoxyribonucleic acid microarrays allow researchers to measure mRNA levels of thousands of genes in a single experiment and could be useful for diagnostic purposes in patients with acute myeloid leukaemia (AML). We assessed the feasibility of the AML profiler (Skyline™ Array) in genetic stratification of patients with de novo AML and compared the results with those obtained using the standard cytogenetic and molecular approach.

Diagnostic bone marrow from 31 consecutive de novo AML cases was used to test MLL‐PTD, FLT3‐ITD and TKD, NPM1 and CEBPAdm mutations. Purified RNA was used to assess RUNX1‐RUNX1T1, PML‐RARα and CBFβ‐MYH11 rearrangements. RNA remnants underwent gene expression profiling analysis using the AML profiler, which detects chromosomal aberrations: t(8;21), t(15;17), inv(16), mutations (CEBPAdm, ABD‐NPM1) and BAALC and EVI1 expression. Thirty cases were successfully analysed with both methods. Five cases had FLT3‐ITD. In one case, a t(8;21) was correctly detected by both methods. Four cases had inv(16); in one, the RNA quality was unsatisfactory and it was not hybridized, and in the other three, the AML profiler detected the genetic lesion — this being a rare type I translocation in one case. Two cases with acute promyelocytic leukaemia were diagnosed by both methods. Results for NPM1 mutations were concordant in all but two cases (2/11, non‐ABD mutations). Analysis of costs and turnaround times showed that the AML profiler was no more expensive than the conventional molecular approach. These results suggest that the AML profiler could be useful in multicentre trials to rapidly identify patients with AML with a good prognosis. Copyright © 2016 John Wiley & Sons, Ltd.
A comparison of experiences, competencies and development needs of doctor managers in Kenya and the United Kingdom (UK)
Authors: Ireri Salome Kathomi , Walshe Kieran , Benson Lawrence , Mwanthi Mutuku
Published: May 2016

Purpose

The purpose of the research was to explore and compare the experiences, leadership and management competencies and development needs of doctor managers in Kenya and the UK.

Design/methodology

A comparative study d258esign involving fieldwork in Kenya and the UK was adopted. Data were collected using a multi‐method approach: qualitative interviews and a survey with doctor managers. The template method was used for qualitative data analysis while appropriate statistical tests in SPSS were used for quantitative data analysis.

Findings

The findings of the study add to the knowledge on experiences of doctor managers, competencies and development needs. Ways of addressing some of the difficulties are proposed.

Research limitations/implications

The study highlights issues of a comparative study across different cultures and the issue of bias that is associated with self reports.

Practical and social Implications

It is assumed that management decisions have much in common and the training and socialisation of doctors as professionals is somewhat similar. This paper explores if there are any experiences that are transferable and if competency frameworks in healthcare used in developed countries are transferable to a developing country.

Originality/value

The study gives baseline knowledge and insight into the experiences, competencies and development needs of doctor managers in a developing country and adds to existing knowledge on doctor managers in the UK. This study has also provided currently the only international study comparing the experiences, competencies and development needs of doctors in management.
Inverse associations of dietary fiber and menopausal hormone therapy with colorectal cancer risk in the Multiethnic Cohort Study
Authors: Park Song‐Yi , Wilkens Lynne R. , Kolonel Laurence N. , Henderson Brian E. , Le Marchand Loïc
Published: May 2016

In the Multiethnic Cohort Study, we previously reported that dietary fiber intake was inversely associated with colorectal cancer risk in men only. In women, the inverse relationship was weaker and appeared to be confounded by menopausal hormone therapy (MHT). We re‐examined this observation with a greatly increased power. Using Cox proportional hazards models, we analyzed data from 187,674 participants with 4,692 cases identified during a mean follow‐up period of 16 years. In multivariable‐adjusted models, dietary fiber intake was inversely associated with colorectal cancer risk in both sexes: HR = 0.73, 95% CI: 0.61–0.89 for highest vs. lowest quintile, ptrend = 0.0020 in men and HR = 0.76, 95% CI: 0.62–0.91, ptrend = 0.0067 in women. Postmenopausal women who ever used MHT had a 19% lower risk of colorectal cancer (95% CI: 0.74–0.89) compared with MHT never users. In a joint analysis of dietary fiber and MHT, dietary fiber intake was associated with a lower colorectal cancer risk in MHT never users (HR = 0.75, 95% CI: 0.59–0.95, ptrend = 0.045), but did not appear to further decrease the colorectal cancer risk of MHT ever users (ptrend = 0.11). Our results support the overall protective roles of dietary fiber and MHT against colorectal cancer and suggest that dietary fiber may not lower risk further among women who ever used MHT. If confirmed, these results would suggest that MHT and dietary fiber may share overlapping mechanisms in protecting against colorectal cancer.
Effects of γ‐Irradiation on the Molecular Structures and Functions of Human Serum Albumin
Authors: Hu Xinxin , Song Wei , Li Wei , Guo Changying , Yu Zehua , Liu Rutao
Published: May 2016

In this paper, we use spectroscopic methods (fluorescence spectroscopy, UV absorption spectroscopy, and circular dichroism (CD) spectroscopy) to elucidate the effects of reactive oxygen species generated by γ‐irradiation on the molecular properties of human serum albumin (HSA). The results of fluorescence spectroscopy indicated that oxidation by γ‐irradiation can lead to conformational changes of HSA. Data of CD spectra suggested that with the increase of radiation dose the percentage of α‐helix in HSA has decreased. The determination of protein hydrophobicity showed that the effective hydrophobicity of HSA decreased up to 62% compared to the native HSA solution due to the exposure to the γ‐irradiation. Furthermore, small changes in the esterase‐like activity of HSA were introduced because of oxidation. The content of bityrosine increased markedly, suggesting that the oxidized HSA was aggregated. Moreover, there was no obvious change in the molecular properties of HSA with low γ‐irradiation dose. Changes happened when the irradiation dose exceeded 200 Gy.
Cancer‐specific promoters for expression‐targeted gene therapy: ran, brms1 and mcm5
Authors: Chen Xuguang , Scapa Jacqueline E. , Liu David X. , Godbey W T.
Published: May 2016

Background

To expand the library of promoters that can be used for expression‐targeted gene delivery to cancer cells, the specificity and strength of expression of three cancer‐related gene promoters was evaluated: RAS‐related nuclear protein (Pran), breast cancer metastasis suppressor 1 (Pbrms1) and minichromosome maintenance complex component 5 (Pmcm5).

Methods

The expression of reporter genes under the control of these promoters demonstrated selectivity in cancer cell lines of breast, prostate and ovarian origins versus a panel of normal cell types. The Pran was next used to regulate the expression of a bioactive exon (a constitutively active form of human caspase 3) to induce apoptosis in cancer cells. Further evaluation was performed in an orthotopic model of murine bladder cancer.

Results

The average strengths of reporter expression had relative intensities of 99.8% (Pran), 87.7% (Pbrms1) and 55.8% (Pmcm5) versus the strong Pcmv‐driven positive control. Comparisons of expression‐targeted reporter gene expression for these three promoters versus the clinically interesting promoter for the human telomerase reverse transcriptase gene (PhTERT) yielded an improvement of two‐ to 15‐fold. Following transfection, cell death was evident from morphologic observations and viability assays performed on the cancer cells lines, with little (if any) effects seen when the same genes were delivered to normal cells. Cell viability was reduced by up to 60% after one treatment, with cell death via apoptosis implied by caspase 3 detection. During the in vivo preclinical study, reduced tumor burden, lack of mineralization and decreased inflammation were demonstrated after only three treatments.

Conclusions

The ran, brms1, and mcm5 promoters have the specificity and strength needed for cancer‐specific expression‐targeted gene therapy. pran in particular produced exciting results when coupled with a version of the caspase 3 exon to treat bladder cancer. Copyright © 2016 John Wiley & Sons, Ltd.
Synthesis of a Novel Tri‐enaminone as Building Block for Polyaza‐heterocycles
Authors: Farghaly Thoraya A. , Abdallah Magda A. , Abdel Aziz Mohamed R.
Published: May 2016

The new tri‐enaminone, namely, 3,4‐bis(3‐dimethylamino‐2‐propenoyl)‐1‐[4‐(3‐dimethylamino‐2‐propenoyl)phenyl]‐5‐methyl‐1H‐pyrazole was prepared and used as building block for synthesis of novel polyaza‐heterocycles. The latter compounds were obtained via an efficient one‐pot reaction of the tri‐enaminone with 1,3‐dipoles and various electrophilic and nucleophilic reagents. The structures of the new products were confirmed based on elemental and spectral analyses. Also, alternative synthetic methods were carried out wherever possible as further evidence for some of the newly synthesized products.
Synthesis and Biological Evaluation of New Dipyridylpteridines, Lumazines, and Related Analogues
Authors: Abbas Zina A. A. , Abu‐Mejdad Najwa M. J. , Atwan Zeenah W. , Al‐Masoudi Najim A.
Published: May 2016

Condensation of 4,5‐diaminopyrimidines 2 and 3 with 2,2ʹ‐dipyridil (4) afforded 6,7‐bis(2‐pyridyl)pteridine‐2‐one analogues 5 and 7, respectively. Analogously, 6,7‐bis(2‐pyridyl)luamzine derivatives 13, 15, 17, and 23 were synthesized from reaction of 5,6‐diamino‐2‐thiopyrimidines 13, 14, and 22 with 4, respectively, while condensation of 4,5,6‐triaminopyrimidines (25) or 5,6‐diamino analogue 26 with 4 furnished the 4‐amino‐pteridine analogue 27 and 28, respectively. Thiation of the new pteridines and lumazines afforded the 4‐thio analogues 6, 8, 16, and 24. Treatment of 6 and 8 with methanolic ammonia afforded the 4‐isopterine analogues 9 and 10, respectively. Alkylation of 15 with substituted phenacyl chloride furnished 18 and 19, which cyclized to the thiazolo‐pteridine derivatives 20 and 21, respectively, on treatment with polyphosphoric acid. Alternatively, 27 was prepared from treatment of 24 with methanolic ammonia under drastic conditions. Condensation of 2 or 29 with 2‐oxo‐2‐(thiophen‐2‐yl)acetaldehyde oxime (11) gave the 6‐(2‐thienyl)‐pteridine‐4‐one (12) and 5‐chloro‐2‐(2‐thienyl)pyrido[3,4‐b]pyrazine (31), respectively. All compounds were evaluated for their antiviral activity against the replication of HIV‐1 and HIV‐2 in MT‐4. Some of the synthesized compounds were tested against the bacterial species, Escherichia coli and Staphylococcus aureus, as well as fungal species, Candida tropicalis and Candida albicans.
Fabrication of boronate‐decorated polyhedral oligomeric silsesquioxanes grafted cotton fiber for the selective enrichment of nucleosides in urine
Authors: Gao Li , Wei Yinmao
Published: May 2016

Various cotton fiber based boronate‐affinity adsorbents are recently developed for the sample pretreatment of cis‐diol‐containing biomolecules, but most do not have efficient capacity due to limited binding sites on the surface of cotton fibers. To increase the density of boronate groups on the surface of cotton fiber, polyhedral oligomeric silsesquioxanes were used to modify cotton fiber to provide plentiful reactive sites for subsequent functionalization with 4‐formylphenylboronic acid. The new adsorbent showed special recognition ability towards cis‐diols and high adsorption capacity (175 μg/g for catechol, 250 μg/g for dopamine, 400 μg/g for adenosine). The in‐pipette‐tip solid‐phase extraction was investigated under different conditions, including pH and ionic strength of solution, adsorbent amount, pipette times, washing solvent, and elution solvent. The in‐pipette‐tip solid‐phase extraction coupled with high‐performance liquid chromatography was used to analyze four nucleosides in urine samples. Under the optimal extraction conditions, the detection limits were determined to be between 5.1 and 6.1 ng/mL (S/N  =  3), and the linearity ranged from 20 to 500 ng/mL for these analytes. The accuracy of the analytical method was examined by studying the relative recoveries of analytes in real urine samples with recoveries varying from 83 to 104% (RSD = 3.9–10.2%, n = 3).