bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical study on the Cope rearrangement mechanisms and the homoaromaticity of semibullvalene, barbaralane, and 1,5‐methanosemibullvalene
Authors: Ichikawa Yuka , Sakai Shogo
Published: September 2011

Cope rearrangement mechanisms and the homoaromaticity of semibullvalene, barbaralane, and 1,5‐methanosemibullvalene in the ground and lowest excited states were studied by ab initio methods. In the ground state, the rearrangement reactions of semibullvalene and barbaralane occurred concertedly through the transition states with C2v symmetry, and the transition states had a homoaromatic nature. In particular, the transition state of barbaralane exhibited the strongest homoaromaticity among the three systems treated here. On the other hand, for 7,8‐methanosemibullvalene, the structure with C2v symmetry was not a transition state but one with a stable energy minimum. The energy minimum structure with C2v symmetry had a biradical character. The lowest excited states of semibullvalene and barbaralane were the excitation to the σ* anti‐orbital, 1B2 and 1B1 states, and led to near di‐allyl states. The lowest excitation state of 1,5‐methanosemibullvalene had Cs symmetry and was the A″ state excitation in one side of two allyl parts. Copyright © 2011 John Wiley & Sons, Ltd.
Tailoring block copolymer morphologies via alkyne/azide cycloaddition
Authors: Wei Xinyu , Strzalka Joseph W. , Li Le , Russell Thomas P.
Published: September 2011

We investigated the morphological transitions induced by alkyne/azide Huisgen 1,3‐dipolar cycloaddition reaction in a series of poly(ethylene oxide)‐block‐poly(n‐butyl methacrylate‐random‐propargyl methacrylate) (PEO‐b‐P(nBMA‐r‐PgMA)) diblock copolymers. Studies on the phase behavior of neat diblock copolymers revealed that the interactions between the PEO block and the terminal alkyne groups in the P(nBMA‐r‐PgMA) block significantly affected the miscibility between the two blocks and the crystallization of the PEO block. Phase‐mixed diblock copolymers underwent disorder‐to‐order transitions by blending with Rhodamine B azide and annealing at elevated temperatures. Different morphologies were achieved, not only by controlling the composition of the block copolymer but also by blending the diblock copolymer with different amount of azides. Microphase separated PEO‐b‐P(nBMA‐r‐PgMA) diblock copolymer also exhibited reactivity toward azides, and order‐to‐order transitions were observed. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011
Electronic structures of the Cu2S2 core of the CuA site in cytochrome c oxidase and nitrous oxide reductase
Authors: Takano Yu , Shigeta Yasuteru , Koizumi Kenichi , Nakamura Haruki
Published: September 2011

The CuA site functions as an electron transfer intermediate in cytochrome c oxidase (CcO) and nitrous oxide reductase. X‐ray crystal structures have shown that the CuA site is a binuclear copper site, bridged by two cysteinyl thiolate groups. Each copper ion is coordinated by a histidine side chain and a weaker axial ligand: a methionine side chain or a backbone carbonyl group. The ground state of the oxidized CuA site is strongly related to the singly occupied orbital, as the oxidized state of the CuA site is doublet. Spectroscopic studies have suggested the σu* ground state of the CuA site due to the direct CuCu interaction, facilitating a rapid electron transfer over long distances with low driving forces. In this study, to elucidate what factors are responsible for the stabilization of the σu* ground state of the CuA site, the electronic structures of the Cu2S2 core of the CuA have been studied, using the density functional theory (M06). Our computational results show that the ground state of the Cu2S2 core is the πu state even with a shorter CuCu distance, and that an addition of electrostatic and orbital interactions by ligand coordination stabilizes the σu* state rather than the πu state, because electrostatic repulsion and antibonding orbital interaction between the dσ* orbital of the CuCu dimer and the lone pairs of the coordinating His residues rise the orbital energy of the σu* orbital of the CuA site. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012
Surprises in nonlinear perturbations: Case of a multiple well potential problem
Authors: Dhatt Sharmistha , Bhattacharyya Kamal
Published: September 2011

We study an atypical nonlinear perturbation problem on the lowest three states of a harmonic oscillator. The perturbation is such that the total potential is a single‐well at low values of coupling strength, turns to a double‐well in the intermediate coupling range and finally becomes a triple‐well at high values of the coupling strength. Proceeding via logarithmic perturbation theory, we notice that the perturbation furnishes exact results for both the energy and wave function of the second excited state but shows divergence for the first excited one. However, the ground state wave function is found to be exactly summable to the correct result with a finite energy series. Effects of varying the coupling constant, and hence the number of wells, on energies and wave functions of the concerned states are noted. Our results show further that the perturbed ground state acquires a pre‐exponential factor and, strangely, an exponent same as the second excited state. The origin of such an outcome is analyzed. We also highlight the reason behind the Klauder phenomenon that tells of increased sustenance of memory effects in wave functions, when compared with the Hamiltonian, in the limit of zero coupling strength. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012
Explaining temporal orientation: Evidence from the durability of firms' capital investments
Authors: Souder David , Bromiley Philip
Published: September 2011

In contrast to broad generalizations about the short‐termism of managers, this paper explains changes in the temporal orientation of specific firms over time based on performance relative to aspirations and top management team incentives. We gain empirical traction on temporal orientation by measuring the durability of acquired property, plant, and equipment (asset durability) from reported data on depreciation expense. Consistent with predictions, we find that performance relative to aspirations positively influences asset durability. Surprisingly, we find no evidence that stock‐based compensation produces the same effect. Instead, we find stock‐based compensation lowers asset durability. Copyright © 2011 John Wiley & Sons, Ltd.
Bioconjugated Fluorescent Zeolite L Nanocrystals as Labels in Protein Microarrays
Authors: Li Zhen , Luppi Gianluigi , Geiger Albert , Josel Hans‐Peter , De Cola Luisa
Published: September 2011

Zeolite L nanocrystals, as inorganic host material containing hydrophobic fluorophore N,N′‐bis(2,6‐dimethylphenyl)perylene‐3,4,9,10‐tetracarboxylic diimide in the unidirectional channels, are developed as new labels for biosensor systems. The external surface of the particles is modified with carboxylic acid groups for conjugation to primary amines of biomolecules such as antibodies. Anti‐digoxigenin (anti‐DIG) is selected to be immobilized on zeolite L via N‐hydroxysulfosuccinimide ester linker. Together with DIG, it serves as a good universal binding pair for diverse analyte detection owing to the high binding affinity and low background noise. The conjugates are characterized by the dynamic light scattering technique for their hydrodynamic diameters and by enzyme‐linked immunosorbent assay for antigen–antibody binding behavior. The characterizations prove that anti‐DIG antibodies are successfully immobilized on zeolite L with their binding activities maintained. The microarray fluorescent sandwich immunoassay based on such nanocrystalline labels shows high sensitivity in a thyroid‐stimulating hormone assay with the lower detection limit down to the femtomolar range. These new fluorescent labels possess great potential for in vitro diagnostics applications.
Promoting integrity through standards of practice
Authors: Komives Susan R. , Arminio Jan
Published: September 2011

The Council for the Advancement of Standards in Higher Education (CAS) has created standards that can be used to increase structural soundness and ethical excellence in institutional programs and services.
Give in or get out? Responding to professional challenges
Authors: Young Robert B.
Published: September 2011

The author interviewed six leaders about challenges to their professional integrity. The themes from those interviews are offered in this chapter.
Subdiaphragmatic vagotomy induces a functional change in visceral Aδ primary afferent fibers in rats
Authors: Furuta Sadayoshi , Matsumoto Kenjiro , Horie Syunji , Suzuki Tsutomu , Narita Minoru
Published: September 2011

Vagal nerves modulate not only physical homeostasis, but also pain transmission. It has been reported that subdiaphragmatic vagal dysfunction causes visceral pain. However, the functional changes in nociceptive primary afferent fibers under such visceral pain soon after subdiaphragmatic vagal dysfunction are not fully documented. The present study was designed to investigate changes in the sensitivity of primary afferent fibers in the distal colon using a Neurometer which individually stimulates C, Aδ and Aβ fibers. Under stimulation with a handmade stimulus electrode in the distal colon, the current threshold in the distal colon was recorded with high reproducibility. Subdiaphragmatic vagotomy significantly decreased the current threshold of Aδ fibers in the distal colon with no change in the sensitivity of C or Aβ fibers. These results suggest that vagal dysfunction at an early stage may cause, at least in part, hypersensitivity of visceral Aδ fibers. Synapse, 2012. © 2011 Wiley‐Liss, Inc.
Copper(II) Melonates Cu3[C6N7(NCN)3]2·8H2O and [Cu(C2H8N2)2]3[C6N7(NCN)3]2·4H2O – Using the Terminal Cyano Group of the[C6N7(NCN)3]3– Ion for Complexation
Authors: Clauss Corinna , Schmidt Horst , Schwarzer Anke , Kroke Edwin
Published: September 2011

Abstract. Copper melonate Cu3[C6N7(NCN)3]2·8H2O (2a) was synthesized by a metathesis reaction of potassium melonate with copper(II) in aqueous solution. A related copper melonate [Cu(C2H8N2)2]3[C6N7(NCN)3]2·4H2O (2b) was obtained from an aqueous potassium melonate solution containing copper(II) and ethylenediamine. The crystal structure of 2b was determined by X‐ray diffraction analysis (triclinic, P$\bar{1}$, a = 6.8035(5), b = 12.6931(8), c = 14.9636(10) Å,α = 67.215(5), β = 79.273(6), γ = 87.206(6)°, V = 1170.17(14) Å3). In contrast to already reported crystal structures of melonates copper ions are coordinated only to the terminal nitrogen atoms of the cyanamide functionality of the melonate anion. Both copper(II) melonates 2a and 2b were further characterized by FT‐IR and 13C MAS NMR spectroscopy, TG/DTA, and elemental analysis. Whereas dehydrated 2a is stable up to 500 °C, 2b shows less thermal stability.
Synthesis and Structures of Zinc(II) and Cadmium(II) Complexes with (η6‐Benzenecarboxylate) Chromium Tricarbonyl and Pyrazole Derivatives
Authors: Murugesapandian Balasubramanian , Roesky Peter W.
Published: September 2011

Abstract. Reaction of zinc acetate with four different substituted pyrazoles (3,5‐dimethyl pyrazole (3,5‐Me2PzH), 3,5‐di‐tert‐butyl pyrazole (3,5‐tBu2PzH), 3,5‐diphenyl pyrazole (3,5‐Ph2PzH), and 5‐methyl‐3‐phenyl pyrazole (3‐Ph‐5‐Me‐PzH)) followed by treatment with(η6‐benzenecarboxylic acid) chromium tricarbonyl afforded the bimetallic zinc‐chromium complexes [Zn{(η6‐C6H5COO)Cr(CO)3}2(3,5‐Me2PzH)2], [Zn{(η6‐C6H5COO)Cr(CO)3}2(3,5‐tBu2PzH)2], [Zn{(η6‐C6H5COO)Cr(CO)3}2(3,5‐Ph2PzH)2], and [Zn{η6‐C6H5COO)Cr(CO)3}2(3‐Ph‐5‐Me‐PzH)2]. The corresponding bimetallic cadmium‐chromium complexes [Cd{(η6‐C6H5COO)Cr(CO)3}2(3,5‐Me2PzH)2] and [Cd{(η6‐C6H5COO)Cr(CO)3}2(3,5‐tBu2PzH)2] were obtained by using cadmium acetate as starting material. The pyrazole rings and the carboxylate {(η6‐C6H5COO)Cr(CO)3}– anion act as monodentate ligand in the zinc complexes, whereas a monodentate and bidentate coordination of the {(η6‐C6H5COO)Cr(CO)3}– anion is observed in the cadmium complexes.
Syntheses of Iron Carbonyl N‐Heterocyclic Stannylene Complexes
Authors: Jana Anukul , Azhakar Ramachandran , Roesky Herbert W. , Objartel Ina , Stalke Dietmar
Published: September 2011

The reaction of the β‐diketiminato tin(II) compound LSnCl (1) [L = CH{CMe(NAr)}2, Ar = 2,6‐iPr2C6H3] with diiron nonacarbonyl, Fe2(CO)9, at room temperature led to the iron carbonyl complex LSn(Cl)Fe(CO)4 (2). Complex 2 reacted with AgOSO2CF3 (AgOTf) to yield LSn(OTf)Fe(CO)4 (3). Complex 3 could also be prepared by the reaction of LSnOTf (4) with Fe2(CO)9 at room temperature. Compounds 2 and 3 were characterized by elemental analysis, NMR spectroscopy, and mass spectrometry. Both complexes were unambiguously established by single‐crystal X‐ray structural analysis.
Ligand Exchange Processes on Solvated Beryllium Cations, VI. Hydrogen Chalcogenide Exchange on [Be(Chelate)Sol2]2+ (Chelate: CH3–O–C2H4–O–CH3, CH3–S–C2H4–S–CH3, CH3–Se–C2H4–Se–CH3; Sol: H2O, H2S, H2Se)
Authors: Walther Markus , Dücker‐Benfer Carlos , Puchta Ralph
Published: September 2011

Following work from Dehnicke et al. on the binding of Be2+ to crown ethers, solvent addition, and solvent exchange energies were calculated (B3LYP/6‐311+G**) for solvated beryllium complexes with bidentate ligands CH3–O–C2H4–O–CH3 [1,2‐bis(methoxy)ethane], CH3–S–C2H4–S–CH3 [1,2‐bis(methio)ethane], and CH3–Se–C2H4–Se–CH3 [1,2‐bis(methylselanyl)ethane], and H2O, H2S, and H2Se as solvents. All water exchange reactions for the different bidentate ligands show no variation, with energies of addition to the second coordination sphere of around –25 kcal·mol–1 and exchange activation energies of around 19 kcal·mol–1. Substituting water by H2S and H2Se in [(CH3–O–C2H4–O–CH3)Be(Solvent)2]2+ lowered the energy for addition of a solvent molecule in the second coordination sphere to –12 kcal·mol–1 and the exchange activation energy to 12 kcal·mol–1. All reaction mechanisms were found to be of the associative interchange (Ia) type.
1,2‐Diaza‐3,5‐diborolidine CH2BR1‐(NR2)2‐BR1: Potentielle Vorstufen zu cyclischen Diborylcarben‐Liganden
Authors: Weber Lothar , Förster Jan Benjamin , Stammler Hans‐Georg , Neumann Beate
Published: September 2011

The reaction of the aminohaloboranes (Me2N)(R)BX (1) (a: R = Ph, X = Cl; b: R = Me, X = Br; c: R = iPr, X = Cl) with the di‐Grignard reagent (BrMg)2CH2 in ethyl ether/benzene mixtures afforded the diborylmethanes [(Me2N)(R)B]2CH2 (2) (a: R = Ph; b: R = Me; c: R = iPr), which were subsequently converted into the corresponding bis(chloroboryl)methanes [(Cl)(R)B]2CH2 (3) (a: R = Ph; b: R = Me; c: R = iPr). Base‐assisted cyclocondensation of 3a–c with 1,2‐diisopropylhydrazine afforded 1,2‐diisopropyl‐1,2‐diaza‐3,5‐diorgano‐3,5‐diborolidines (4) (a: R = Ph; b: R = Me; c: R = iPr). Derivative 4a was deprotonated by potassium bis(trimethylsilyl)amide to give (1,2‐diisopropyl‐1,2‐diaza‐3,5‐diphenyl‐3,5‐diborolidinyl)potassium (5). Attempts to introduce a halogen atom to the carbon bridge between the two boron atom by treating 5 with either iodine or 1,2‐dibromoethane failed. Instead, bis(1,2‐diisopropyl‐1,2‐diaza‐3,5‐diphenyl‐3,5‐diborolidinyl) (C‐C) (6) was formed. In contrast to this, C‐silylation of the heterocycle to give 7 was effected by reaction of salt 5 with trimethylsilyl chloride. Similarly, treatment of HgCl2 with two molar equivalents of 5 gave rise to the formation of bis(1,2‐diisopropyl‐1,2‐diaza‐3,5‐diphenyl‐3,5‐diborolidinyl)mercury (8). The novel compounds were characterized by elemental analyses and various spectroscopic methods (1H‐, 11B{1H}‐, 13C{1H} NMR, MS). The molecular structures of 4a and 6–8 were elucidated by X‐ray diffraction analyses.
Medical imaging in personalised medicine: a white paper of the research committee of the European Society of Radiology (ESR)
Authors:   European Society of Radiology
Published: September 2011

The future of medicine lies in early diagnosis and individually tailored treatments, a concept that has been designated ‘personalised medicine’ (PM), i.e. delivering the right treatment to the right patient at the right time. However, the value of medical imaging in PM is frequently underestimated, as many policy makers forget the all-important right location in the PM paradigm. Medical imaging has always been personalised as it provides individual assessment of the location and extent of an abnormality, and in the future it will prove fundamental to almost all aspects of PM. Stratification based on imaging biomarkers can help identify individuals suited for preventive intervention and can improve disease staging. In vivo visualisation of locoregional physiological, biochemical and biological processes using molecular imaging can detect diseases in pre-symptomatic phases or facilitate individualised drug delivery. Furthermore, imaging is essential to patient-tailored therapy planning, therapy monitoring and follow-up of disease progression, as well as targeting non-invasive or minimally invasive treatments, especially with the rise of theranostics. For PM to reach its full potential, medical imaging must be an integral part. Radiologists need to be prepared for this new paradigm as it will mean changes in training, in research and in clinical practice.
Adolescent temperament and parental control in the development of the adolescent decision making in a Chilean sample⋆
Authors: Pérez J. Carola , Cumsille Patricio
Published: September 2011

The study analyzes the way in which adolescents’ temperamental characteristics interact with parental control to shape adolescent decision making development. A sample of high‐school Chilean adolescents (N = 391) answered a self‐report questionnaire that included measures of behavioral autonomy (the extent to which adolescents make decisions in personal and prudential domains), parental behavioral and psychological control, and temperamental characteristics. A path analysis model indicated that adolescents’ anger–frustration had a direct association with decision‐making in the personal and prudential domains; fearfulness had an inverse association with adolescent decision‐making, but only in the prudential domain. Perceived psychological control was associated with adolescents’ reduced decision‐making autonomy in the personal domain, while perceived behavioral control was associated with less adolescent autonomy in both personal and prudential domains. Additionally, a moderation effect was found such that the association of parental behavioral control on decision‐making in the prudential domain was dependent on the adolescent fearfulness level.
ON MINIMAL DEGREES OF PERMUTATION REPRESENTATIONS OF ABELIAN QUOTIENTS OF FINITE GROUPS
Authors: FRANCHI CLARA
Published: September 2011

For a finite group G, we denote by μ(G) the minimum degree of a faithful permutation representation of G. We prove that if G is a finite p-group with an abelian maximal subgroup, then μ(G/G′)≤μ(G).
Sensibilism, Psychologism, and Kant's Debt to Hume
Authors: Chance Brian A.
Published: September 2011

Hume's account of causation is often regarded a challenge Kant must overcome if the Critical philosophy is to be successful. But from Kant's time to the present, Hume's denial of our ability to cognize supersensible objects, a denial that relies heavily on his account of causation, has also been regarded as a forerunner to Kant's critique of metaphysics. After identifying reasons for rejecting Wayne Waxman's recent account of Kant's debt to Hume, I present my own, more modest account of this debt, an account that seeks to unite the two very different pictures of Kant's relationship to Hume sketched above.
Modeling of Solder Fatigue Failure due to Ductile Damage
Authors: Aluru K. , Wen F.-L. , Shen Y.-L.
Published: September 2011

A numerical study is undertaken to simulate failure of solder joint caused by cyclic shear deformation. A progressive ductile damage model is incorporated into the rate-dependent elastic-viscoplastic finite element analysis, resulting in the capability of simulating damage evolution and eventual failure through crack formation. It is demonstrated that quantitative information of fatigue life, as well as the temporal and spatial evolution of fatigue cracks, can be explicitly obtained.
Structural Synthesis by Method of Centers in Force Formulation under Size and Stress Constraints
Authors: Farshi B. , Alinia-ziazi A.
Published: September 2011

This paper studies a novel approach to optimize trusses and truss-like structures for minimum weight design. It is based on the force method of analysis which is incorporated inside the optimization routine. The design variables in force formulation are the member cross sectional areas and the redundant forces in each load condition. The optimization method used is the method of center points using the inscribed hyperspheres to the feasible-usable design space. By incorporating the analysis step as part of the optimization problem, a separate structural solution phase, which is necessary in all other methods, is avoided resulting in large computational savings. In this article the simplest form of structuresi.e.trusses are treated to illustrate the efficacy of the method. Stress limits on the members as well as limitations on their sizes, and linking among them, under several load conditions have been considered. Combination of the method of center points and force formulation results in a viable routine for structural optimization. Comparison of the example results with those obtained by others clearly shows the effectiveness and novelty of the proposed method.
Stark effects on bound polarons in polar rectangular quantum wires
Authors: Song Tie-Lei , Liang X. X.
Published: September 2011

The impurity binding energy in a polar rectangular quantum wire under an applied electric field is studied by a variational approach. The electron- and ion-longitudinal-optical (LO) phonon interactions are both taken into account in the calculations. The numerical results for the GaAs rectangular quantum wires show that the binding energies and Stark energy-shift are both sensitive to the size, shape of the wire section, and the position of the impurity. The binding energy increases with decreasing the section area. The LO phonon effect lowers the binding energy of the on-center impurity but raises that of the impurity near the wire surface, and gives a qualitatively similar contribution to the Stark effect.
Frequency response of graphene phonons to heating and compression
Authors: Yang X. X. , Li J. W. , Zhou Z. F. , Wang Y. , Zheng W. T. , Sun Chang Q.
Published: September 2011

The thermally softened and the mechanically stiffened graphene phonons have been formulated from the perspective of bond order-length-strength correlation with confirmation of the C–C bond length in the single-layer graphene contracting from 0.154 to 0.125 nm and the binding energy increasing from 0.65 to 1.04 eV. Matching theory to the measured temperature- and pressure-dependent Raman shift has derived that the Debye temperature drops from 2230 to 540 K, the atomic cohesive energy drops from 7.37 to 3.11 eV/atom, and the binding energy density increases from 250 to 320 eV/nm3 compared with the respective quantities of bulk diamond.
Bosentan for digital ulcers in patients with systemic sclerosis
Authors: NAGAI Yayoi , HASEGAWA Michiko , HATTORI Tomoyasu , OKADA Etsuko , TAGO Osamu , ISHIKAWA Osamu
Published: September 2011

Recurrent digital ulcers are manifestations of vascular disease in patients with systemic sclerosis (SSc). We report six patients with severe digital ulcers who were treated with bosentan administered p.o., 62.5–125 mg daily. The mean duration from the diagnosis of SSc to the initiation of bosentan was 9.5 years, and the observation period after bosentan administration was from 7 months to 4.5 years. In case 1, neither new digital ulcers nor Raynaud’s phenomenon developed for 4.5 years. In case 2, digital ulcers recurred after the discontinuation of bosentan; however, re‐administration of bosentan lead to the improvement. In cases 3–5 with recurrent digital ulcers, no new lesions have developed. In these five patients, pain evaluated by visual analog scale was significantly reduced. In three patients, bosentan was discontinued because of severe liver dysfunction. These results suggest that bosentan is an effective treatment for refractory digital ulcers associated with SSc; however, liver function should be carefully monitored. Compared to the doses of bosentan used to treat pulmonary hypertension, relatively lower doses may effectively control painful digital ulcer/gangrene in patients with SSc.
Analysis of 256 cases of basal cell carcinoma after either one‐step or two‐step surgery in a Japanese institution
Authors: GOTO Mizuki , KAI Yoshitaka , ARAKAWA Shoko , OISHI Masaki , ISHIKAWA Kazushi , ANZAI Saburou , HATANO Yutaka , OKAMOTO Osamu , KATAGIRI Kazumoto , FUJIWARA Sakuhei , SHIMIZU Fumiaki , KATO Aiko , SHIBUYA Hiromi , ESHIMA Nobuoki , TERASHI Hiroto
Published: September 2011

Basal cell carcinoma (BCC) is a common skin cancer that arises from the cells of the basal layer of the epithelium or from the external root sheath of the hair follicle. In the present report, 256 cases treated surgically between 1999 and 2008 in our department were retrospectively analyzed. The most frequent BCC locations included the face (77.8%), especially the nose (26.9%) and eyelids (21.5%). Incomplete excisions occurred in 21 cases. Two patients experienced local recurrence; one of these patients exhibited a bone metastasis while the other had a metastasis of the parotid gland without the local recurrence. The rate of local BCC recurrence was 0.78%, which is lower than that described in previous reports. We categorized BCC into four histological types: superficial, solid, adenoid and infiltrative. The solid type was the most frequent histological type (62.1%). For preventive recurrence, we treated BCC patients with two‐step surgery when the tumor was large or histologically invasive. At the first step, we excised the tumor with a sufficient safety margin, and at the second step, we performed reconstruction after the histological confirmation that no remnant malignant cells were in the tumor margins. In the present report, no local recurrence occurred in patients following the two‐step surgery. Therefore, two‐step surgery is recommended for tumors at locations and with histological types related to frequent recurrence.
The safety and tolerability of spironolactone in patients with mild to moderate chronic kidney disease
Authors: Edwards Nicola C. , Steeds Richard P. , Chue Colin D. , Stewart Paul M. , Ferro Charles J. , Townend Jonathan N.
Published: September 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Spironolactone has recently been shown to exert beneficial effects on the cardiovascular and renal systems. To date, its use in patients with chronic kidney disease has been limited due to potential risks of hyperkalaemia and declining renal dysfunction.

WHAT THIS STUDY ADDS

• Non‐diabetic patients with early stage chronic kidney disease (CKD) on concomitant therapy with angiotensin converting enzyme (ACE) inhibition or angiotensin II receptor blockade with a serum potassium of <5.5 mmol/L and no history of hyperkalaemia who were randomized in a trial to treatment with spironolactone for 40 weeks had low rates of serious hyperkalaemia (<1%) and worsening renal function (<3%). Frequent biochemical monitoring is required for the initial 4 weeks but only routine monitoring is needed thereafter.

AIM Mineralocorticoid receptor blockade (MRBs) in combination with angiotensin converting enzyme (ACE) inhibitors and angiotensin‐II receptor blockade (ARBs) improve prognostic markers of cardiovascular and renal disease in early stage chronic kidney disease (CKD). Concerns relating to the safety and tolerability of MRBs in CKD may limit their use in a non clinical trial setting.

METHODS In the Chronic Renal Impairment in Birmingham II study, 115 patients with non‐diabetic early stage CKD (eGFR 30–89 ml/min/1.73m2) received 25 mg daily of spironolactone for 4 weeks before randomization to continuing treatment or placebo for a further 36 weeks. All patients were on ACE inhibitors and/or ARB therapy. Potassium and renal function were checked at weeks 1, 2, 4, 8, 16, 28 and 40. The incidence of hyperkalaemia, significant renal dysfunction (reduction eGFR ≥25%) and adverse effects was assessed.

RESULTS After 40 weeks of treatment the incidence of serious hyperkalaemia (K+≥6.0 mmol/L) was <1%. A potassium 5.5–5.9 mmol/L occurred on ≥1 occasion over follow‐up in 11 patients (nine on spironolactone) and was predicted by baseline potassium ≥5.0 mmol/L and eGFR ≤45 ml/min/1.73m2. Over follow‐up, three patients experienced significant renal dysfunction but no patients withdrew due to intolerance or side effects. Changes in potassium, eGFR and systolic blood pressure were most apparent in the first 4 eeks.

CONCLUSION Spironolactone was well tolerated in selected patients with early stage CKD. Strict monitoring over the first month of treatment followed by standard surveillance as for ACE inhibitors and ARBs is suggested.
Discrimination of agonist and antagonist forms of CXCL10 in biological samples
Authors: Casrouge A , Bisiaux A , Stephen L , Schmolz M , Mapes J , Pfister C , Pol S , Mallet V , Albert M L
Published: September 2011

The ready access to commercially available multiplex assays and the importance of inflammation in disease pathogenesis has resulted in an abundance of studies aimed at identifying surrogate biomarkers for different clinically important questions. Establishing a link between a biomarker and disease pathogenesis, however, is quite complex, and in some instances this complexity is compounded by post-translational modifications and the use of immunoassays that do not always discriminate between the different forms of the same protein. Herein, we provide a detailed description of an assay system that has been established to discriminate the agonist form of CXCL10 from the NH2-terminal truncated form of the molecule generated by dipeptidylpeptidase IV (DPP4) cleavage. We demonstrate the utility of this assay system for monitoring agonist and antagonist forms of CXCL10 in culture supernatant, patient plasma and urine samples. Given the important role of CXCL10 in chronic inflammatory diseases and its suggested role as a predictive marker in managing patients with chronic hepatitis C, asthma, atopic dermatitis, transplantation, tuberculosis, kidney injury, cancer and other diseases, we believe that our method will be of general interest to the research and medical community.
Therapeutic potential of carbon monoxide in multiple sclerosis
Authors: Fagone P , Mangano K , Coco M , Perciavalle V , Garotta G , Romao C C , Nicoletti F
Published: September 2011

Carbon monoxide (CO) is produced during the catabolism of free haem, catalyzed by haem oxygenase (HO) enzymes, and its physiological roles include vasodilation, neurotransmission, inhibition of platelet aggregation and anti-proliferative effects on smooth muscle. In vivo preclinical studies have shown that exogenously administered quantities of CO may represent an effective treatment for conditions characterized by a dysregulated immune response. The carbon monoxide-releasing molecules (CORMs) represent a group of compounds capable of carrying and liberating controlled quantities of CO in the cellular systems. This review covers the physiological and anti-inflammatory properties of the HO/CO pathway in the central nervous system. It also discusses the effects of CORMs in preclinical models of inflammation. The accumulating data discussed herein support the possibility that CORMs may represent a novel class of drugs with disease-modifying properties in multiple sclerosis.
Late‐night salivary cortisol for diagnosis of Cushing’s syndrome by liquid chromatography/tandem mass spectrometry assay
Authors: Erickson Dana , Singh Ravinder J. , Sathananthan Airani , Vella Adrian , Bryant Sandra C.
Published: September 2011

Background  Late‐night salivary cortisol (LNSC) measurements have been increasingly used by physicians as an initial diagnostic test for evaluation of patients with clinical suspicion of Cushing’s syndrome (CS). Published studies include various numbers of cases, controls and importantly, various assay methods (vast majority various immunoassays), as well as various methods to generate cut‐points.

Materials and Methods  The retrospective study evaluated the diagnostic utility of LNSC measurements in 249 patients evaluated for possibility of CS because of various clinical conditions using liquid chromatography/tandem mass spectrometry method (LC‐MS/MS). CS was confirmed in 47 patients (18·9%) and excluded in 202 (81·1%) patients at the time of analysis.

Results  Late‐night salivary cortisol was abnormal or >2·8 nmol/l in 35 of 47 patients with CS; sensitivity of 74·5% and elevated in 20 of 202 patients who were found not to have CS; specificity 90·1%. Using receiver‐operator characteristic statistics for calculation of the most optimal sensitivity and specificity, the cut‐off based on this data was LNSC > 2·1 nmol/l with sensitivity of 83·0% and specificity of 84·2%.

Conclusion  Analysis of data at one referral institution showed somewhat limited sensitivity of LNSC for diagnosis of CS using current reference ranges.
Effectiveness of antioxidants (propolis, blueberry, vitamin E) associated with verapamil in the medical management of Peyronie’s disease: a study of 151 cases
Authors: Paulis G. , D’Ascenzo R. , Nupieri P. , De Giorgio G. , Orsolini G. , Brancato T. , Alvaro R.
Published: September 2011

A total of 151 patients (age: 24–74 years, mean: 55 ± 10.3) diagnosed with Peyronie’s disease were enrolled in a non‐surgical treatment. In addition to medical histories and physical examinations, all patients underwent the following tests: penile ultrasound, IIEF questionnaire and photographic documentation. The penile curvature was measured by taking a photograph during maximum erection. All 151 patients were treated at different times and with different combinations of drugs, and afterwards, they were clinically studied and divided into five different treatment groups: 1st = verapamil (injection + iontophoresis) + vitamin E + topical diclofenac + blueberries; 2nd = verapamil (injection + iontophoresis) + vitamin E + topical diclofenac + propolis; 3rd = verapamil (injection) + vitamin E + topical Diclofenac; 4th = verapamil (iontophoresis) + vitamin E + topical diclofenac; 5th = verapamil (injection + iontophoresis) + topical diclofenac + blueberries + propolis. All patients were treated for 6 months after which they underwent the same follow‐up tests as performed prior to the treatment. The following was achieved: group 1 had the most reduction in plaque size (−66.4%; p = 0.000), group 2 obtained the highest rate where penile curvature disappeared (24.5%; p = 0.019); the best results with reference to decrease in curvature angle were reached by the 2nd group (−14°) and group 1 obtained −9.6° (p = 0.000).
Variable offspring size as an adaptation to environmental heterogeneity in a clonal plant species: integrating experimental and modelling approaches
Authors: Charpentier Anne , Anand Madhur , Bauch Chris T.
Published: September 2011

1. The production of variably sized offspring has been hypothesized to be adaptive to temporal variability in environmental conditions.

2. This is difficult to verify empirically, and theoretical models are typically generic and not parameterized with data from real populations; studies integrating theoretical and empirical approaches to this problem are rare.

3. Here, we present experimental data on the growth of Scirpus maritimus, a clonal aquatic macrophyte that grows through vegetative extensions involving tubers.

4. The experiments show that offspring fitness (biomass productivity) is dependent on environmental conditions (water depth).

5. Experimental data indicate that variation in offspring (tuber) sizes can be approximated by a lognormal distribution.

6. We use these data to develop a different equation model of S. maritimus growth to test whether producing variably sized offspring is adaptive. The model compares fitness under the lognormal strategy to several hypothetical strategies with qualitatively different variance in offspring size.

7. The model results suggest that lognormal variation in S. maritimus tuber size may be adaptive to the temporal variation in water levels that characterize its natural Mediterranean environment.

8. We illustrate how the underlying principles that lend adaptive value to offspring size variation may apply to other species experiencing similar environmental conditions.

9. Synthesis. Close integration of data and theoretical models creates a unique tool for investigating the adaptive value of life‐history traits in clonal aquatic plants.
Preliminary evidence of an association between the functional c‐kit rs6554199 polymorphism and achalasia in a Turkish population
Authors: Alahdab Y. O. , Eren F. , Giral A. , Gunduz F. , Kedrah A. E. , Atug O. , Yilmaz Y. , Kalayci O. , Kalayci C.
Published: September 2011

Background  C‐kit‐positive interstitial cells of Cajal (ICC) of the lower esophageal sphincter are reduced in achalasia. Two functional gene polymorphisms (rs2237025 and rs6554199) within the c‐kit gene may affect its transcriptional activity. In this pilot study, we hypothesized that these polymorphisms would be associated with achalasia.

Methods  Genomic DNA was extracted and real‐time PCR reactions were used to determine the rs2237025 and rs6554199 c‐kit polymorphisms in 88 Turkish patients with achalasia and 101 healthy controls.

Key Results  The frequency of the T allele of rs6554199 was significantly higher in patients with achalasia [odds ratio (OR): 1.55; 95% confidence interval (CI), 1.03–2.34; P = 0.038] compared with the G allele. Under a dominant model of inheritance, the carriage of at least one T allele was significantly more frequent in patients with achalasia (80.7%) than in controls (65.3%; OR: 2.21; 95% CI, 1.13–4.33; P = 0.022). No association of the c‐kit rs2237025 polymorphism with achalasia was detected.

Conclusions & Inferences  Despite the small sample size and the possibility of a false positive finding, our preliminary data support the hypothesis that the T allele of the c‐kit rs6554199 polymorphism may be associated with achalasia in the Turkish population. These findings need to be replicated in other racial‐ethnically diverse populations.
Diazepam promotes choice of abstinence in cocaine self‐administering rats
Authors: Augier Eric , Vouillac Caroline , Ahmed Serge H.
Published: September 2011

When facing a choice between cocaine and a potent, albeit inessential, non‐drug alternative (i.e. water sweetened with saccharin), most cocaine self‐administering rats abstain from cocaine in favor of the non‐drug pursuit, regardless of the dose available and even after extended drug use. Only a minority continues to take the drug despite the opportunity of making a different choice and increasing stakes. This pattern of individual variation could suggest that the majority of rats are resilient to addiction, taking cocaine by default of other options. Only a minority would be vulnerable to addiction. This study tested the hypothesis that rats choose to refrain from cocaine self‐administration because cocaine would be conflictual, having both rewarding and anxiogenic properties. Contrary to this hypothesis, however, we report here that diazepam—a broad‐spectrum benzodiazepine anxiolytic—did not decrease, but instead, further increased cocaine abstinence. Interestingly, although diazepam decreased locomotion, rats adapted to this effect by spending more time near the lever associated with the preferred reward, a behavior that minimized the need for locomotion at the moment of choice. When responding for cocaine or saccharin was analyzed separately, we found that diazepam decreased responding for cocaine without affecting responding for saccharin. Finally, the abstinence‐promoting effects of diazepam were also induced in cocaine‐preferring rats treated chronically with diazepam. Overall, this study demonstrates that abstinence from cocaine cannot be explained away by the anxiogenic effects of cocaine, thereby reinforcing the notion of resilience to addiction. It also supports the use of benzodiazepines in the treatment of cocaine addiction.
Oral immunotherapy with immunodominant T‐cell epitope peptides alleviates allergic reactions in a Balb/c mouse model of egg allergy
Authors: Rupa P. , Mine Y.
Published: September 2011

To cite this article: Rupa P, Mine Y. Oral immunotherapy with immunodominant T‐cell epitope peptides alleviates allergic reactions in a Balb/c mouse model of egg allergy. Allergy 2012; 67: 74–82.

Background:  Allergen‐specific T‐cell epitopes are obvious targets for immunotherapeutic interventions in allergic disease. T‐cell epitope peptides given orally may provide a practical way of inducing tolerance and preventing allergy.

Objective:  This study investigates oral immunotherapy (OIT) with T‐cell epitope peptides of the dominant egg‐white allergen ovomucoid (Ovm) in a Balb/c mouse model of egg allergy.

Methods:  Groups of mice were orally sensitized to Ovm and subsequently administered Ovm T‐cell epitopes [single peptide 157–171 (SP) or multiple peptide (157–171)3 (MP)], followed by oral challenge with Ovm. Outcomes post oral challenge were measured as clinical signs, serum histamine, antibody activity (IgG, IgE, IgG1, IgG2, IgA), cytokines (IL‐4, IFN‐γ, IL‐12p70, IL‐10, TGF‐β, and IL‐17), and T regulatory cells (Tregs).

Results:  Clinical signs were less frequent in both SP and MP groups (P ≤ 0.05). Specific IgE was less and IgA was more in both groups; however, SP‐treated mice had less histamine and IgG1 and more IgG2‐related antibodies indicating a bias toward the type‐1 response (P ≤ 0.05). Concentration of type‐2 cytokine interleukin‐4 (IL‐4) was significantly less in both groups and IL‐12p70 and IL‐10 were more in SP‐treated mice (P ≤ 0.001). Interferon‐γ, IL‐17, and TGF‐β did not differ significantly. There was significant increase in the percentage of CD4+FOXP3+ and CD4+CD25+ cells in the SP group, indicating the significant role of Tregs in immune regulation.

Conclusion:  In summary, we demonstrated that OIT with SP and MP comprising the immunodominant regions of Ovm was safe and significantly reduced subsequent frequency of allergy to Ovm, and validated potential use of Ovm T‐cell epitope as an immunoregulator.
First Detection of Crown Gall Disease on Florida Hopbush Caused by Agrobacterium tumefaciens in Italy
Authors: Polizzi Giancarlo , Aiello Dalia , Scuderi Giuseppe , Guarnaccia Vladimiro , Cirvilleri Gabriella
Published: September 2011

During the period from 2008 to 2011, symptoms similar to crown gall disease have been detected in potted Dodonaea viscosa cv. ‘Purpurea’ plants in several nurseries located in Catania province (Italy). Gram‐negative bacteria were consistently isolated from gall tissues taken from diseased plants and identified through cultural, biochemical and molecular tests. The obtained isolates were oxidase positive, non‐fluorescent on King’s B medium, utilized mannitol, and were able to grow at 37°C and on nutrient agar containing 2% NaCl. Based on the nutrient profiles revealed by the BIOLOG system, the isolates were identified as Agrobacterium tumefaciens with a probability of 99% and a similarity of 0.61. Furthermore, genomic amplifications were performed by PCR on DNA extracted from representative isolates, with a couple of primers targeting sequences of the Ti plasmid located within the virD region. To our knowledge, this is the first report of occurrence and outbreak of a crown gall disease caused by A. tumefaciens on D. viscosa.
Analysis of Differentially Expressed Genes in Ovaries of Polytocous versus Monotocous Dairy Goats Using Suppressive Subtractive Hybridization
Authors: An XP , Hou JX , Li G , Peng JY , Liu XQ , Liu HY , Xiao WP , Wang JG , Song YX , Cao BY
Published: September 2011

Contents

In this study, suppressive subtractive hybridization (SSH) was performed to screen differentially expressed genes in ovarian tissues between polytocous and monotocous goats. From the SSH cDNA library, we obtained 29 differentially expressed sequence tags (ESTs) that have high similarity with known genes in the public database, which were involved in signal transduction, transcriptional regulation, cellular molecular dynamics, cytoskeleton, metabolism and oxidation–reduction. In addition, one novel EST that has no similarity with known genes in the public database was obtained. Eight ESTs, TIMP1, NUCB1, OAZ1, CXXC5, CAPNS2, ATP5A1, Z and RPL5, were further examined for the reproducibility of the SSH data by the real‐time quantitative PCR. The results confirmed an increased expression of respective mRNA in ovarian tissues of polytocous goats compared with those of monotocous goats. The study has identified several genes (known or unknown) that may have effect on follicular development, ovulation and egg activation in goats.
Guidelines for non‐medical care providers to manage the first steps of emergency triage of elderly evacuees
Authors: Takahashi Takashi , Iijima Katsuya , Kuzuya Masafumi , Hattori Hideyuki , Yokono Koichi , Morimoto Shigeto
Published: September 2011

On 11 March 2011, a strong earthquake occurred off of Japan's Pacific coast and hit northeastern Japan. The earthquake was followed by huge tsunamis, which destroyed many coastal cities. As a result, the Study Group on Guidelines for the First Steps and Emergency Triage to Manage Elderly Evacuees quickly established guidelines enabling non‐medical care providers (e.g. volunteer, helpers, and family members taking care of elderly relatives), public health nurses, or certified social workers to rapidly detect illnesses in elderly evacuees, and 20 000 booklets were distributed to care providers in Iwate, Miyagi, and Fukushima prefectures. The aim of this publication is to reduce susceptibility to disaster‐related illnesses (i.e. infectious diseases, exacerbation of underlying illnesses, and mental stress) and deaths in elderly evacuees. Geriatr Gerontol Int 2011; 11: 383–394.