bluuebunny/crossref_metadata_2025 huggingface dataset:
Doping and Atomic Site Substitution in the Dielectric Ceramics Ti(Al)O2 Rutile and (1−x)Ca2/5Sm2/5TiO3–xLi1/2Sm1/2TiO3 Perovskite
Authors: Yamashita Toru , Barry John , Taylor Richard
Published: November 2009

Temperature‐stable, high‐permittivity (high‐dielectric constant) ceramics are used as resonators for microwave telecommunications. Research and development in this area is aimed at increasing the dielectric constant (in order to reduce component size) while maintaining very high quality factor (low dielectric loss). This present work is a synchrotron X‐ray powder diffraction study of high quality factor, high permittivity ceramics of the Ti(Al)O2 and (1−x)Ca2/5Sm2/5TiO3–xLi1/2Sm1/2TiO3 families. The synchrotron powder diffraction was used to investigate doping of Al onto the Ti site in Ti(Al)O2. It was found that the lattice parameters in Ti(Al)O2 are not affected by the Al doping. Although this null result does not give any evidence for substitution of Al on the Ti site, it does not exclude the possibility that a small proportion of the Al ions do substitute for Ti in Ti(Al)O2. In (1−x)Ca2/5Sm2/5TiO3–xLi1/2Sm1/2TiO3 the variation of lattice parameters and crystal structure versus x, and the possibility of substitution of Li onto the Ti site were investigated. Single phase samples with the orthorhombic CaTiO3 perovskite structure were obtained for 0.20<x<0.50. It was found that the unit cell volume increased in an inverse linear relationship with the (decreasing) vacancy concentration. Rietveld analysis of the powder diffraction data shows that there is no substitution of Li on the Ti site in (1−x)Ca2/5Sm2/5TiO3–xLi1/2Sm1/2TiO3.
Structural and Electrical Properties of Lead‐Free Perovskite Ba(Al1/2Nb1/2)O3
Authors: Prasad Kamal , Chandra Kumar Prabhat , Bhagat Sanjay , Choudhary Shambhu Nath , Kulkarni Ajit R.
Published: November 2009

Lead‐free perovskite Ba(Al1/2Nb1/2)O3 was prepared by conventional ceramic fabrication technique at 1350°C/5 h in air atmosphere. The crystal symmetry, space group and unit cell dimensions were determined from the experimental results using FullProf software whereas crystallite size and lattice strain were estimated from Williamson‐Hall approach. X‐ray diffraction analysis of the compound indicated the formation of a single‐phase monoclinic structure with the space group P2/m. EDAX and SEM studies were carried out in order to evaluate the quality and purity of the compound. Permittivity data showed low‐temperature coefficient of capacitance (TCC=14%) up to 100°C. To find a correlation between the response of the real system and idealized model circuit composed of discrete electrical components, the model fittings were presented using the impedance data. Complex impedance analyses suggested the dielectric relaxation to be of non‐Debye type. The correlated barrier‐hopping model was used to successfully explain the mechanism of charge transport in Ba(Al1/2Nb1/2)O3.
Synthesis and Room Temperature Photoluminescence of Mesoporous Zirconia with a Tetragonal Nanocrystalline Framework
Authors: Mondal Aparna , Zachariah Ajesh , Nayak Priyadarshini , Nayak Bibhuti B.
Published: November 2009

Mesoporous ZrO2 with a tetragonal (t) nanocrystalline framework was synthesized using zirconium propoxide as the zirconium precursor and cetyltrimethylammonium bromide as pore‐directing agent and subsequent calcination of the inorganic/organic intermediate. The Raman spectrum showed six distinct peaks at 146, 268, 325, 480, 615, and 645 cm−1, which further confirm t‐structure of the mesoporous ZrO2. Fourier transform infrared spectroscopy analysis reveals that mesoporous ZrO2 prepared at 500°C is template free. The mesoporous t‐ZrO2 possesses narrowly distributed pore size (2–11 nm) with average pore diameter of 5 nm and surface area of 65 m2/g. A photoluminescence band centered at 419 nm under excitation at 285 nm wavelength at room temperature is attributed to the ionized oxygen vacancy in t‐ZrO2 in the mesoporous structure. The combined effects of grain/pore size, oxygen vacancies and mesoporous wall strain–energy play important role in stabilizing the t‐nanocrystalline framework of mesoporous ZrO2. In comparison with the mesoporous ZrO2 materials stabilized by chemical treatment, the present route is simpler and resulted in mesoporous ZrO2 with crystalline framework.
Hydrothermal Synthesis of Alpha Alumina (α‐Al2O3) Powders: Study of the Processing Variables and Growth Mechanisms
Authors: Suchanek Wojciech L.
Published: November 2009

Alpha alumina (α‐Al2O3) powders and α‐Al2O3/boehmite (γ‐AlOOH) mixtures with controlled γ‐AlOOH contents were synthesized hydrothermally under alkaline or acidic conditions at 380°–435°C for 1–10 days, under 6.9–14.5 MPa pressure, from concentrated precursors without stirring. The precursors were formed by mixing different types of aluminum hydroxides with water, and optionally with α‐Al2O3 seeds, hydrogen peroxide, sulfuric acid, dopants (i.e., KMnO4), and/or other additives. The experiments were performed on industrial scale in large production autoclaves. The synthesized α‐Al2O3 powders exhibited up to 100% phase purity, 99.98% chemical purity, equiaxed morphology, low aggregation levels, narrow crystallite size distributions with primary particle sizes ranging between 100 nm and 40 μm, and high reproducibility. Precursor types, seeds, chemical additives, and temperature/time of the hydrothermal synthesis were found to govern properties of the powders. Different growth mechanisms for nanosized and rough powders are discussed. Results of this study enable the use of hydrothermal α‐Al2O3 powders in a multitude of applications, and make their hydrothermal production a commercial reality.
Influence of Sodium Chloride and Dibasic Sodium Phosphate Salt Matrices on the Anatase–Rutile Phase Transformation and Particle Size of Titanium Dioxide Powder
Authors: Roy Banasri , Fuierer Paul Anton
Published: November 2009

The influence of sodium chloride (NaCl) and dibasic sodium phosphate (Na2HPO4·2H2O, DSP) on the phase transformation and particle size of titanium dioxide powder had been investigated. The salt matrix was shown to suppress both the amorphous to anatase transition and the anatase to rutile transition. DSP was particularly effective. Irrespective of the additives, transformation versus time curves of the anatase to rutile conversion were observed to be sigmoidal, and were interpreted in terms of a first order, nucleation‐growth controlled phenomenon. Analysis of these curves using appropriate rate laws yielded activation energies for nucleation of ∼4.3 eV for NaCl salt matrix and ∼8.6 eV for DSP salt matrix, compared with ∼3.2 eV for a sample with no salt. Activation energies for the growth or propagation stage were ∼5 and ∼8.9 eV for NaCl and DSP powders, respectively, compared with ∼3.8 eV for no salt. In the solid state, salt matrices suppressed the particle growth as well. These behaviors, in general are thought to be governed by the presence of salt impurities, especially anions chemisorbed at the surface.
Compositional Substitutions and Aliovalent Doping of BaTiO3‐Based Thin Films on Nickel Foils Prepared by Chemical Solution Deposition
Authors: Bretos Iñigo , Schneller Theodor , Waser Rainer , Hennings Detlev F. , Halder Sandip , Thomas Florian
Published: November 2009

Several strategies were evaluated focusing on the optimum reliability of thin‐film ceramic capacitors derived from different compositions based on BaTiO3(BT) and prepared by chemical solution deposition onto nickel foils. Film crystallization was carried out at 800°C under reducing conditions to prevent the detrimental oxidation of the metal electrode while allowing the formation of the pure perovskite phase. In a first approach, compositional modifiers were introduced into the system, yielding to Ba(Ti0.7Zr0.3)O3(BTZ) and (Ba0.7Sr0.3)TiO3(BST) solid solutions. Despite the lower permittivities obtained with respect to pure BT, dielectric losses and leakage current densities in these films were observed to improve. With the aim of further optimizing these features, the second approach focuses on the defect chemistry of BST films by incorporation of either donor–acceptor cations (Mn2+and Nb5+) or single rare‐earth elements (Dy3+or Y3+“magic ions”) into the perovskite. The leakage conduction in the associated capacitors is revealed to effectively decrease in the first case, whereas doping with rare‐earth cations does not substantially improve the dielectric properties of the ceramics. Processing effects related to the thin‐film configuration, rather distant from the classical scenario used within the technology of multilayer bulk ceramic capacitors, also account for the final properties obtained in the films of this work.
Impedance Spectroscopy Studies of Fresnoites in BaO–TiO2–SiO2 System
Authors: Rangarajan Badri , Bharadwaja Srowthi S. N. , Furman Eugene , Shrout Thomas , Lanagan Michael
Published: November 2009

The electrical properties of the fresnoite BaO–TiO2–SiO2 system were studied over a range of amorphous and crystalline microstructures using as‐quenched glass (BTS‐gl), partially crystallized glass (BTS‐pc, heat treated at 740°C for 100 min) and fully crystallized glass ceramic (BTS‐gc, heat treated at 750°C for 180 min). Combination of impedance and moduli plots along with equivalent circuit models were utilized in an attempt to understand the contributions arising from different regions in the glass ceramic, i.e. the glassy matrix, crystalline phase, and crystal–glass interface region. Electrical conductivity of the samples exhibited frequency dispersions at different temperatures suggesting localized motion of ions. The activation energies calculated from dc resistivity–temperature plots (Edc) and relaxation frequency–temperature plots (Ef) seem to increase as the degree of crystallinity increases suggesting that ionic transport becomes more difficult in crystallized glasses.
Blue‐emitting AlN:Eu2+ Powder Phosphor Prepared by Spark Plasma Sintering
Authors: Do Hyoung‐SeoK , Choi Sung‐Woo , Hong Seong‐Hyeon
Published: November 2009

Blue‐emitting AlN:Eu2+ powder phosphor was synthesized by spark plasma sintering (SPS) using AlN, Si3N4, and Eu2O3 as the starting materials, and its luminescence properties were investigated. A single‐phase Eu‐ and Si‐co‐doped AlN powder was successfully fabricated by SPS in the range of 1650°–1800°C for 5 min. The AlN:Eu2+ obtained exhibited a strong blue emission at 480 nm under the excitation of λexc=340 nm and an electron beam. The highest photoluminescence intensity was observed in the phosphor sintered at 1700°C, which was comparable to that of the phosphor prepared by gas pressure sintering at 1750°C for 4 h.
Perfectly (001)‐ and (111)‐Oriented (Ba,Sr)TiO3 Thin Films Sputtered on Pt/TiOx/SiO2/Si Without Buffer Layers
Authors: Yang Lihui , Wang Genshui , Dong Xianlin , Rémiens Denis
Published: November 2009

We report the growth of (001)‐ and (111)‐oriented (Ba,Sr)TiO3 (BST) films on Pt/TiOx/SiO2/Si substrates by RF magnetron sputtering without buffer layers. Interestingly, it was observed that the crystallographic orientation of prepared films strongly depended on O2/(Ar+O2) mixed ratios (OMR) during deposition. The samples with OMR=0% showed a perfect (001) orientation, while those with OMR ranging from 10% to 50% showed a preferential (111) orientation. The perfectly (111)‐oriented BST film deposited with OMR=30% exhibited a broader grain size distribution than the (001) textured BST film. At ±400 kV/cm, high tunability of 52% and 68% can be achieved for (001)‐ and (111)‐oriented BST films, respectively.
The Piezoelectric and Dielectric Properties of 0.3Pb(Ni1/3Nb2/3)O3–xPbTiO3–(0.7−x)PbZrO3Ferroelectric Ceramics Near the Morphotropic Phase Boundary
Authors: Cao Ruijuan , Li Guorong , Zeng Jiangtao , Zhao Suchuan , Zheng Liaoying , Yin Qingrui
Published: November 2009

0.3Pb(Ni1/3Nb2/3)O3−xPbTiO3–(0.7−x)PbZrO3(x=0.33–0.43) piezoelectric ceramics were prepared by the one‐step solid‐state reaction method. X‐ray diffraction analysis showed the coexistence of rhombohedral and tetragonal phases at the compositionx=0.39, which is the morphotropic phase boundary (MPB) for this system. The dielectric, ferroelectric, and piezoelectric properties of 0.3Pb(Ni1/3Nb2/3)O3–xPbTiO3–(0.7−x)PbZrO3were investigated as a function of the content of PbTiO3. The ceramics at MPB showed large remnant polarization, low coercive field, and good piezoelectric properties. The results showed that piezoelectric ceramics with high piezoelectric constant and high Curie temperature also can be obtained in Pb(Ni1/3Nb2/3)O3–PbTiO3–PbZrO3system with low Pb(Ni1/3Nb2/3)O3content.
Crystal Structure and Ferroelectric Behaviors of Ba5SmTi3Ta7O30 and Ba4Sm2Ti4Ta6O30 Tungsten Bronze Ceramics
Authors: Cao Mu Xin , Zhu Xiao Li , Liu Xiao Qiang , Chen Xiang Ming
Published: November 2009

The crystal structure and dielectric characteristics were evaluated for Ba4Sm2Ti4Ta6O30 and Ba5SmTi3Ta7O30 ceramics. The X‐ray diffraction patterns confirmed the tetragonal tungsten bronze structure with space group P4bm. A normal ferroelectric phase transition was observed at 332 K for the former, while the typical relaxor ferroelectric behavior with a spin glass nature was determined for the latter, where a broad permittivity peak with a strong frequency dispersion was observed around 150 K, which followed the Vogel–Fulcher relationship well. These different dielectric behaviors originated from the different crystal structures governed by the occupancy configuration of cations at A1 and A2 sites.
De la protección laboral a la vulnerabilidad social. Reformas neoliberales en la Argentina
Authors: NOVICK Marta , LENGYEL Miguel , SARABIA Marianela
Published: November 2009

Los autores analizan el conjunto de reformas neoliberales instrumentado en la Argentina durante la década de 1990, poniendo el énfasis en las políticas laborales, sus consecuencias sobre la dinámica del mercado de trabajo y el bienestar de los hogares. Para dar una mirada integral al período trazan una versión sucinta de las estrategias llevadas a cabo tanto en la etapa anterior de sustitución de importaciones como con posterioridad al estallido de la crisis política, económica y social de 2001–2002, que constituyó el punto de inflexión para la emergencia de un nuevo conjunto de políticas económicas y sociales caracterizado por un fuerte intento de articulación y de inclusión social a través del empleo.
Flexibilización sociolaboral. Lo que aprendió el Brasil en los años noventa
Authors: POCHMANN Marcio
Published: November 2009

La trayectoria sociolaboral que recorrió el Brasil entre los decenios de 1930 y de 1970 dio un viraje a raíz de la crisis de la deuda de 1981–1983. Empezó a desmantelarse entonces el sistema de protección social y laboral construido durante esos cincuenta años al calor de la expansión urbana e industrial y del trabajo asalariado. Pero las políticas de corte neoliberal adoptadas no aportaron el dinamismo económico necesario, pues se agravaron el desempleo y la precariedad laboral. Desde finales de 2002 ha comenzado el abandono progresivo del proyecto de sociedad neoliberal.
El modelo social chileno comienza a cambiar
Authors: RIESCO Manuel
Published: November 2009

El Estado modernizó el modelo social chileno siguiendo dos estrategias: el desarrollismo (1924–1973) y el llamado «Consenso de Washington» (1973–2008). Durante el primer período, el Estado impulsa las políticas sociales universales y la reforma agraria, aparte de construir la infraestructura económica e institucional. Tras el golpe de 1973 se desmantelan servicios públicos y se reprime el movimiento laboral. El rumbo se modera tras el fin de la dictadura en 1990, pero perdura la resistencia a la regulación estatal y el desequilibrio en perjuicio del trabajador. El modelo está cambiando ahora debido a la democratización y a la crisis mundial.
Una reforma híbrida. La política social y laboral en el Uruguay de 1985 a 2008
Authors: ALEGRE Pablo , FILGUEIRA Fernando
Published: November 2009

Desde que el Uruguay retorna a la democracia en 1985 se transforma radicalmente el país. Hay adaptaciones por defecto al nuevo entorno internacional y reformas en favor del libre mercado, aunque los cambios son muy heterogéneos en ritmo y contenido. A diferencia de otros países en la región, el Uruguay no sigue una ruta de reforma nítidamente neoliberal, sino un camino híbrido. Al final del período nos encontramos con un régimen laboral liberalizado y un edificio social de tres pisos en donde conviven el mercado, el viejo Estado social corporativo y el nuevo Estado social con beneficiarios muy delimitados.
Expression of chromogranins A, B, and C (secretogranin II) in human adrenal medulla and in benign and malignant pheochromocytomas An immunohistochemical study with region‐specific antibodies
Authors: PORTELA‐GOMES GUIDA MARIA , STRIDSBERG MATS , GRIMELIUS LARS , FALKMER URSULA G. , FALKMER STURE
Published: November 2009

In a recent immunohistochemical study of pheochromocytomas, a difference was observed between benign and malignant pheochromocytomas in their expression in different parts of the chromogranin (Cg) A molecule. The purpose of the present study was to extend the investigations by including two other members of this Cg family, CgB and C. Twenty‐five patients operated on for clinicopathologically benign pheochromocytomas, and four for metastasizing pheochromocytomas, were studied. Expression of the different Cg regions was studied immunohistochemically by means of region‐specific antibodies: four raised against CgA epitopes, five against CgB, and two against CgC. Adrenal medulla parenchyma from three surgical adrenalectomy specimens was used as non‐neoplastic control. All cells of normal adrenal medulla were immunoreactive to all 11 region‐specific Cg antibodies. In the pheochromocytomas, variations in the expression pattern occurred, but no significant quantitative differences were noted between benign and malignant tumours. Nevertheless, in all four malignant pheochromocytomas, the antibodies raised against the C‐terminal regions of both CgB and CgC visualised a noticeable population of large spindle‐shaped tumour cells, characterised by elongated processes. This cell type occurred in all four malignant pheochromocytomas but only in one benign tumour. Their structure and immunoreactivity differed from those of the sustentacular cells in the pheochromocytoma parenchyma. The use of region‐specific antibodies raised against epitopes in the C‐terminal region of CgB and CgC can facilitate the diagnosis of malignant pheochromocytoma.
Evaluation of radiographs, clinical signs and symptoms associated with pulp canal obliteration: an aid to treatment decision
Authors: Oginni Adeleke O. , Adekoya‐Sofowora Comfort A. , Kolawole Kikelomo A.
Published: November 2009

Abstract –  Pulp canal obliteration (PCO) is a sequela of tooth trauma. The dental clinician faced with this condition has to make a difficult decision. The aim of this study was to evaluate the clinical signs and symptoms associated with teeth with PCO and to assess the status of the periapical tissues using the periapical index (PAI) as an aid in making a treatment decision. The study included teeth diagnosed with PCO in patients with a history of traumatic injury to the involved teeth. Histories of associated signs and symptoms including pain, swelling and drainage from a sinus tract were elicited. Tooth color, sensibility to electric pulp testing, mobility and percussion tenderness were recorded. The periapical status was assessed using the PAI. Two hundred and seventy‐six teeth were diagnosed with PCO. One hundred and fifty‐seven (56.9%) and 119 (43.1%) demonstrated partial or total PCO, respectively. Yellow discoloration presented most frequently, occurring in 186 (67.4%) teeth. Sixty‐two (33.3%) of these had developed periapical lesions and reacted negatively to sensibility testing. Fifty‐seven (30.7%) of these teeth presented radiographically with a normal periapical appearance and reacted normally to sensibility testing, whereas 67 (36.0%) presented with small changes in the periapical bone pattern and reacted in the high normal range to sensibility testing. Teeth with PAI scores ≤2 presented with occasional spontaneous pain. Teeth with PAI scores ≥3 presented with clinical symptoms and signs ranging from pain on percussion to spontaneous pain, and slight swelling to sinus tract drainage. Based on the findings of this study, endodontic treatment should be initiated in teeth with tenderness to percussion, PAI scores ≥3 and a negative response to sensibility testing.
Dental hygienists’ work environment: motivating, facilitating, but also trying
Authors: Candell A , Engström M
Published: November 2009

To cite this article:
 
Int J Dent Hygiene 8, 2010; 204–212 DOI: 10.1111/j.1601‐5037.2009.00420.x Candell A, Engström M. Dental hygienists’ work environment: motivating, facilitating, but also trying

Abstract:  The aim of the present study was to describe dental hygienists’ experiences of their physical and psychosocial work environment. The study was descriptive in design and used a qualitative approach. Eleven dental hygienists participated in the study and data were collected during spring 2008 using semi‐structured interviews. The material was analysed using qualitative content analysis. The results showed that the dental hygienists experienced their work environment as motivating and facilitating, but at the same time as trying. The three categories revealed a theme: Being controlled in a modern environment characterized by good relationships. Motivating factors were the good relationship with co‐workers, managers and patients, seeing the results of your work, having your own responsibility and making your own decisions. The new, pleasant and modern clinics, good cooperation between co‐workers and varying duties were described as facilitating factors. The trying factors, as described by the dental hygienists, were above all being controlled by time limits or by some elements of the work, such as teamwork. The dental hygienists also felt stress because appointments were too‐short. To conclude, the participants described their work environment as trying in several ways, despite the modern clinics and good relationships.
AWMF‐Leitlinie Nr. 013/066 Diagnostik und Therapie der zirkumskripten Sklerodermie
Authors: Kreuter Alexander , Krieg Thomas , Worm Margitta , Wenzel Jörg , Gambichler Thilo , Kuhn Annegret , Aberer Elisabeth , Scharffetter‐Kochanek Karin , Hunzelmann Nicolas
Published: November 2009

Localized scleroderma is a rare autoimmune disease with primary affection of the skin, and occasional involvement of the fat tissue, muscle, fascia, and bone. Depending on the clinical subtype, the spectrum of skin lesions ranges from singular plaque lesions to severe generalized or linear subtypes which may lead to movement restrictions and permanent disability. This German S1‐guideline proposes a classification of localized scleroderma that, considering the extent and depth of fibrosis, distinguishes limited, generalized, linear, and deep forms of localized scleroderma, together with its associated subtypes. The guideline includes a description of the pathogenesis, of differential diagnoses, and particular aspects of juvenile localized scleroderma, as well as recommendations for histopathologic, serologic, and biometric diagnostic procedures. Based on studies of topical and systemic treatments as well as phototherapy for localized scleroderma published in international literature, a treatment algorithm was developed which takes account of the different subtypes and the extent of disease.
Hypoxia‐inducible factor‐1α blocks differentiation of malignant gliomas
Authors: Lu Huimin , Li Yan , Shu Minfeng , Tang Jianjun , Huang Yijun , Zhou Yuxi , Liang Yingjie , Yan Guangmei
Published: November 2009

Aberrant differentiation is a characteristic feature of neoplastic transformation, while hypoxia in solid tumors is believed to be linked to aggressive behavior and poor prognosis. However, the possible relationship between hypoxia and differentiation in malignancies remains poorly defined. Here we show that rat C6 and primary human malignant glioma cells can be induced to differentiate into astrocytes by the well‐known adenylate cyclase activator forskolin. However, hypoxia‐inducible factor‐1α expression stimulated by the hypoxia mimetics cobalt chloride or deferoxamine blocks this differentiation and this effectiveness is reversible upon withdrawal of the hypoxia mimetics. Importantly, knockdown of hypoxia inducible factor‐1α by RNA interference restores the differentiation capabilities of the cells, even in the presence of cobalt chloride, whereas stabilization of hypoxia‐inducible factor‐1α through retarded ubiquitination by von Hippel‐Lindau tumor suppressor gene silence abrogates the induced differentiation. Moreover, targeting of HIF‐1 using chetomin, a disrupter of HIF‐1 binding to its transcriptional co‐activator CREB‐binding protein (CBP)/p300, abolishes the differentiation‐inhibitory effect of hypoxia‐inducible factor‐1α. Administration of chetomin in combination with forskolin significantly suppresses malignant glioma growth in an in vivo xenograft model. Analysis of 95 human glioma tissues revealed an increase of hypoxia‐inducible factor‐1α protein expression with progressing tumor grade. Taken together, these findings suggest a key signal transduction pathway involving hypoxia‐inducible factor‐1α that contributes to a differentiation defect in malignant gliomas and sheds new light on the differentiation therapy of solid tumors by targeting hypoxia‐inducible factor‐1α.

Structured digital abstract

MINT‐7292117: CBP (uniprotkb:Q6JHU9) physically interacts (MI:0915) with Hif1a (uniprotkb:O35800) by anti bait coimmunoprecipitation (MI:0006)
TransLISA, a novel quantitative, nonradioactive assay for transcription factor DNA‐binding analyses
Authors: Vuori Kristiina A. , Ahlskog Johanna K. , Sistonen Lea , Nikinmaa Mikko
Published: November 2009

Transcription factors are DNA‐binding proteins that regulate key biological processes. Their interactions with DNA are commonly analyzed with gel‐based electrophoretic mobility shift assay (EMSA) using radioactively labeled probes. Within various fields of research, there exists an increasing demand to develop assays with faster sample throughput combined with improved sensitivity, increased analytical range, and precise quantification. Here, we describe the development and performance of a 384‐well plate immunoassay, termed TransLISA, which is a novel homogeneous assay for rapid and sensitive quantification of the DNA‐binding activity of transcription factors in cell and tissue lysates. TransLISA outperforms EMSAs, because it eliminates the need to use radioactive chemicals and allows fast and precise quantification of DNA‐binding activity of transcription factors from large number of samples simultaneously. We have used TransLISA to demonstrate the DNA‐binding activity of heat shock factor 1, representing a well‐known model of inductive transcriptional regulatory responses, but the method is easily adaptable for the study of any transcription factor. Thus, TransLISA can replace EMSAs and may be used in various applications and research fields where quantitative, cost‐effective and large‐scale measurements of the DNA‐binding activity of transcription factors are required, including screening of responses in multiple treatments in cellular and molecular biology, evolutionary research, environmental monitoring, and drug discovery.
Cardiac and Haemodynamic Effects of Tacrolimus in the Halothane‐Anaesthetized Dog
Authors: Kise Hiroaki , Nakamura Yuji , Hoshiai Minako , Sugiyama Hisashi , Sugita Kanji , Sugiyama Atsushi
Published: November 2009

Abstract:  Tacrolimus (FK506) is a potent immunosuppressant widely used for the treatment of patients with solid organ transplantation and autoimmune diseases. The present study investigated the cardiac, haemodynamic and electrophysiological effects of tacrolimus. Tacrolimus in doses of 0.01 and 0.1 mg/kg was infused over 10 min. with a pause of 20 min. in halothane‐anaesthetized dogs under monitoring of plasma drug concentrations (n = 5). Sub‐therapeutic dose of 0.01 mg/kg hardly affected any of the cardiovascular variables except that it slightly delayed the repolarization. The clinically relevant dose of 0.1 mg/kg had negative chronotropic, inotropic and dromotropic effects, and lowered blood pressure by 70 ± 12 mmHg, effects previously ascribed to Ca2+ channel blocking action. Tacrolimus also delayed the repolarization process in a dose‐dependent and reverse use‐dependent manner with an increase in electrical vulnerability. The cardiovascular effects of tacrolimus were enhanced after the cessation of drug infusion, despite a decline in the plasma concentrations. In human embryonic kidney 293 cells, however, only supratherapeutic tacrolimus concentrations (>0.1 μmol/l) inhibited hERG K+ current with a maximum inhibition of 28% at 10 μmol/l, indicating that other mechanisms might have also operated besides direct block of ionic channel function. The present study suggests that tacrolimus has negative chronotropic, inotropic and dromotropic effects in the heart, delays repolarization and lowers blood pressure. Moreover, the monitoring of the actual drug concentration may not necessarily reflect its effects on the cardiovascular system; thus, frequent monitoring of cardiovascular variables may be essential for tacrolimus‐treated patients.
l‐Carnitine Attenuates Cardiac Remodelling rather than Vascular Remodelling in Deoxycorticosterone Acetate‐Salt Hypertensive Rats
Authors: O’Brien Daniel , Chunduri Prasad , Iyer Abishek , Brown Lindsay
Published: November 2009

Abstract:  l‐Carnitine is an important co‐factor in fatty acid metabolism by mitochondria. This study has determined whether oral administration of l‐carnitine prevents remodelling and the development of impaired cardiovascular function in deoxycorticosterone acetate (DOCA)‐salt hypertensive rats (n = 6–12; #p < 0.05 versus DOCA‐salt). Uninephrectomized rats administered DOCA (25 mg every 4th day s.c.) and 1% NaCl in drinking water for 28 days developed cardiovascular remodelling shown as systolic hypertension, left ventricular hypertrophy, increased thoracic aortic and left ventricular wall thickness, increased left ventricular inflammatory cell infiltration together with increased interstitial collagen and increased passive diastolic stiffness and vascular dysfunction with increased plasma malondialdehyde concentrations. Treatment with l‐carnitine (1.2% in food; 0.9 mg/g/day in DOCA‐salt rats) decreased blood pressure (DOCA‐salt 169 ± 2; + l‐carnitine 148 ± 6# mmHg), decreased left ventricular wet weights (DOCA‐salt 3.02 ± 0.07; + l‐carnitine 2.72 ± 0.06# mg/g body‐wt), decreased inflammatory cells in the replacement fibrotic areas, reduced left ventricular interstitial collagen content (DOCA‐salt 14.4 ± 0.2; + l‐carnitine 8.7 ± 0.5# % area), reduced diastolic stiffness constant (DOCA‐salt 26.9 ± 0.5; + l‐carnitine 23.8 ± 0.5# dimensionless) and decreased plasma malondialdehyde concentrations (DOCA‐salt 26.9 ± 0.8; + l‐carnitine 21.2 ± 0.4# μmol/l) without preventing endothelial dysfunction. l‐carnitine attenuated the cardiac remodelling and improved cardiac function in DOCA‐salt hypertension but produced minimal changes in aortic wall thickness and vascular function. This study suggests that the mitochondrial respiratory chain is a significant source of reactive oxygen species in the heart but less so in the vasculature in DOCA‐salt rats, underlying the relatively selective cardiac responses to l‐carnitine treatment.
Drug Dispensing Errors in a Ward Stock System
Authors: Andersen Stig Ejdrup
Published: November 2009

Abstract:  The aim of this study was to determine the frequency of drug dispensing errors in a traditional ward stock system operated by nurses and to investigate the effect of potential contributing factors. This was a descriptive study conducted in a teaching hospital from January 2005 to June 2007. In five wards, samples of dispensed solid drugs were collected prospectively and compared with the prescriptions. Data were evaluated using multivariable logistic regression. Overall, 2173 samples were collected, 95.5% of which were correctly dispensed (95% CI 94.5–96.2). In total, 124 errors in 6715 opportunities for error were identified; error rate of 1.85 errors per 100 opportunities for error (95% CI 1.54–2.20). Omission of a dose was the predominant type of error while vitamins and minerals, drugs for acid‐related diseases and antipsychotic drugs were the drugs most frequently affected by errors. Multivariable analysis showed that surgical and psychiatric settings were more susceptible to involvement in dispensing errors and that polypharmacy was a risk factor. In this ward stock system, dispensing errors are relatively common, they depend on speciality and are associated with polypharmacy. These results indicate that strategies to reduce dispensing errors should address polypharmacy and focus on high‐risk units. This should, however, be substantiated by a future trial.
Dynamic Epigenetic Changes Involved in Testicular Toxicity Induced by Di‐2‐(Ethylhexyl) Phthalate in Mice
Authors: Wu Shengde , Zhu Jing , Li Yasha , Lin Tao , Gan Liqiang , Yuan Xingang , Xiong Jing , Liu Xing , Xu Mingdeng , Zhao Dan , Ma Chao , Li Xuliang , Wei Guanghui
Published: November 2009

Abstract:  The aim of this study was to analyse epigenetic (specifically, DNA methylation) change in testes induced by maternal exposure to di‐2‐(ethylhexyl) phthalate (DEHP) in mice. Testicular dysgenesis syndrome was induced in foetuses by maternal exposure to DEHP. High‐performance liquid chromatography was performed to analyse DNA methylation status, and expression levels of the DNA methyltransferases were examined by quantitative real‐time polymerase chain reaction and western blotting. DEHP significantly had more than 10% relative increase in the global DNA methylation and also increased DNA methyltransferases’ expression. Changes in DNA methylation may play an important role in abnormal testicular function caused by environmental factors such as maternal exposure to DEHP, which may be one possible mechanism of DEHP‐mediated testicular toxicity.
Variability and Impact on Design of Bioequivalence Studies
Authors: Van Peer Achiel
Published: November 2009

Abstract:  In 2008, the European Agency for the Evaluation of Medicinal Products released a draft guidance on the investigation of bioequivalence for immediate release dosage forms with systemic action to replace the former guidance of a decade ago. Revisions of the regulatory guidance are based upon many questions over the past years and sometimes continuing scientific discussions on the use of the most suitable statistical analysis methods and study designs, particularly for drugs and drug products with high within‐subject variability. Although high within‐subject variability is usually associated with a coefficient of variation of 30% or more, new approaches are available in the literature to allow a gradual increase and a levelling off of the bioequivalence limits to some maximum wider values (e.g. 75–133%), dependent on the increase in the within‐subject variability. The two‐way, cross‐over single dose study measuring parent drug is still the design of first choice. A partial replicate design with repeating the reference product and scaling the bioequivalence for the reference variability are proposed for drugs with high within‐subject variability. In case of high variability, more regulatory authorities may accept a two‐stage or group‐sequential bioequivalence design using appropriately adjusted statistical analysis. This review also considers the mechanisms why drugs and drug products may exhibit large variability. The physiological complexity of the gastrointestinal tract and the interaction with the physicochemical properties of drug substances may contribute to the variation in plasma drug concentration‐time profiles of drugs and drug products and to variability between and within subjects. A review of submitted bioequivalence studies at the Food and Drug Administration’s Office of Generic Drugs over the period 2003–2005 indicated that extensive pre‐systemic metabolism of the drug substance was the most important explanation for consistently high variability drugs, rather than a formulation factor. These scientific efforts are expected to further lead to revisions of earlier regulatory guidance in other regions as is the current situation in Europe.
Effects of Selective Serotonin Reuptake Inhibitors on Timolol Metabolism in Human Liver Microsomes and Cryo‐Preserved Hepatocytes
Authors: Volotinen Marjo , Korjamo Timo , Tolonen Ari , Turpeinen Miia , Pelkonen Olavi , Hakkola Jukka , Mäenpää Jukka
Published: November 2009

Abstract: Timolol has been widely used in the treatment of glaucoma. Topically applied, timolol may cause adverse cardiovascular effects due to systemic absorption through the nasolacrimal duct. Timolol is mainly metabolized by cytochrome P450 2D6 (CYP2D6) in the liver. The aim of the present study was to characterize further the metabolism of timololin vitro. Especially the effect of several drugs such as selective serotonin reuptake inhibitors on the metabolism of timolol was evaluated. In human liver microsomes, four timolol metabolites were identified, in cryo‐preserved hepatocytes nine. In bothin vitroexperiments, the hydroxy metabolite M1 was the main metabolite. Thein vivohalf‐life predicted for timolol was 3.7 hr. in cryo‐preserved hepatocytes, corresponding to the half‐life of timolol in humansin vivo. Fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine inhibited the formation of M1 in microsomes with IC50values of 1.4, 2.0, 3.5, 21 and 20 μM, respectively. In human cryo‐preserved hepatocytes, the IC50values for fluoxetine, paroxetine and fluvoxamine were 0.7, 0.5 and 5.9 μM, respectively. In conclusion, compounds known to be potent CYP2D6 inhibitors inhibited timolol metabolism inin vitroexperiments. The present results strongly suggest that fluoxetine and paroxetine may significantly affect the metabolism of timolol alsoin vivoand may thus potentiate the adverse cardiovascular effects of topically administered timolol.
Cardioprotective Effect of SMND‐309, A Novel Derivate of Salvianolic Acid B on Acute Myocardial Infarction in Rats
Authors: Yang Jianxiong , Zhang Guanbo , Tian Jingwei , Li Chunmei , Jiang Wanglin , Xing Yanli , Zhu Haibo , Hou Jian , Xu Hong , Wu Juan
Published: November 2009

Abstract:  (2E)‐2‐{6‐[(E)‐2‐carboxylvinyl]‐2,3‐dihydroxyphenyl}‐3‐(3,4‐dihydroxyphenyl) propenoic acid, a novel compound designated SMND‐309, is a new derivate of salvianolic acid B. The present study was designed to investigate the cardioprotective potential of SMND‐309 and to elucidate the possible mechanisms on the basis of biochemical, histopathological and immunohistochemical studies in a rat model of acute myocardial infarction induced by permanent ligation of the left coronary artery. The results showed that treatment with SMND‐309 via tail vein at doses of 10 and 20 mg/kg significantly prevented the elevation in ST segment level and the increase in serum creatine kinase‐MB, lactate dehydrogenase, alanine aminotransferase and cardiac troponin T content. Meanwhile, SMND‐309 significantly increased the activities of superoxide dismutase, catalase and glutathione peroxidase, decreased the content of malondialdehyde in myocardium, and reduced the myocardium necrosis scores and the number of apoptosis cardiocytes in accordance with the up‐regulated expression of anti‐apoptotic protein, Bcl‐2 and the down‐regulated expression of proapoptotic protein, Bax. Moreover, SMND‐309 exhibits significantly higher potency compared to salvianolic acid B at the same mg/kg but not the same mol/kg. These findings indicate that SMND‐309 has a protective potential against myocardial infarction injury and the protective effects may be due to its scavenging lipid peroxidation products, increasing endogenous antioxidant defence enzymes and attenuating cardiocyte apoptosis.
Expression of Ht2‐related genes in response to the HT‐Toxin of Exserohilum turcicum in Maize
Authors: Wang H. , Li H. , Zhu Z. , Wang X.
Published: November 2009

Complementary DNA amplified fragment length polymorphism (cDNA‐AFLP) analysis was conducted to analyze differential expression of Ht2‐related genes between maize (Zea mays) near‐isogenic lines (NILs), Huangzaosi (HZS) and HuangzaosiHt2 (HZSHt2), following treatment with a crude extract of the HT‐toxin. Twenty‐one transcript‐derived fragments (TDFs), designated H1 to H21, were specifically expressed or upregulated in HZSHt2 following exposure to the HT‐toxin. Among them, 4, 7, 4, 2, 2 and 2 TDFs were detected at 3, 6, 12, 24, 48 and 72 h after treatment, respectively. BLAST analysis showed that H1, H11, H13 and H15 are related to regulation of the defence response to environmental stresses. H3, H6 and H10 are associated with energy metabolism. H5, H17 and H18 are involved in photosynthesis. H9 is similar to ubiquitin‐like domain containing CTD phosphatase. H8, H9, H16 and H20 are probably transcription factors. The genes associated with basal energy metabolism and signal of stress tolerance were mainly expressed at 3 h after treatment. Transcription factor and most genes for stress tolerance were expressed at 6 h after treatment. RT‐PCR analysis demonstrated that H8 was upregulated in HZSHt2 only at 6 h after exposure to the HT‐toxin and H13 was upregulated at 6 and 12 h. The full length cDNAs of H8 (GenBank accession number FJ600319) and H13 (FJ600320) were cloned. The deduced protein encoded by H8 cDNA showed 77% homology to the Plus‐3 domain containing protein, which is found in yeast gene Rtf1. H13 cDNA encodes a QM‐like protein, which is an important protein in plant tolerance to environmental stress. The mechanism regulating the resistance of Ht2 to the HT‐toxin might involve a translation elongation factor or an upregulated QM‐like protein.
Evaluation of Micromechanical Properties of Carbon/Carbon and Carbon/Carbon–Silicon Carbide Composites at Ultralow Load
Authors: Sarkar Soumya , Dey Arjun , Das Probal K. , Mukhopadhyay Anoop K. , Kumar Anil
Published: November 2009

2D carbon fiber (C‐fiber)‐reinforced carbon/carbon (C/C) composites were prepared by vacuum infiltration with coal‐tar pitch followed by carbonization and graphitization in inert atmosphere. Liquid silicon infiltration was done in controlled atmosphere at 1600°C to convert the matrix carbon of the C/C composites into silicon carbide. The 2D C/C and carbon/carbon–silicon carbide (C/C—SiC) composites had density of ∼1.65 and ∼2.32 g/cm3, respectively with corresponding flexural strength of ∼70 and ∼169 MPa, respectively. The local mechanical properties like hardness, Young's modulus, contact pressure, relative stiffness, relative spring back, and indentation energies of the two composites under different loading conditions were measured at an ultra low load of 10 mN using a nanoindentation instrument with a Berkovich indenter. The scatter in the data was treated in terms of the two‐parameter Weibull statistical analysis. The maximum characteristic Young's modulus (∼16 GPa) and hardness (1.20 GPa) was obtained for the C/C–SiC composites in parallel direction of fabric stacking. The elastic rebounce was also the maximum (0.77) for the C/C–SiC composites when loaded in parallel direction of fabric stacking. The extent of structural anisotropy was higher in the C/C–SiC composite than that of the C/C composite.
Anisotropic Dielectric and Electrical Properties of Hot‐Forged SrBi4Ti4O15Ceramics
Authors: Rout Sanjeeb K. , Barhai Prema K. , Sinha Ela , Hussain Ali , Kim W.
Published: November 2009

The effect of grain orientation on the dielectric and electrical properties of SrBi4Ti4O15ceramics are studied by impedance and modulus spectroscopy. The degree of orientation calculated from the X‐ray diffraction pattern is found to be 94.2% along thec‐axis of the crystal structure. The ratio of permittivity along the perpendicular to parallel direction is found to be ∼2.5 at the Curie temperature. The nonsuperimposition of the normalized Z″ and M″ versus frequency plot revealed that the conduction is localized and deviate from ideal Debye‐like behavior. The conduction mechanism has been explained on the basis of jump relaxation model.
Expression of the Japanese oak silkworm Antheraea yamamai fibroin gene in the domesticated silkworm Bombyx mori
Authors: Kobayashi Isao , Kojima Katsura , Sezutsu Hideki , Uchino Keiro , Tamura Toshiki
Published: November 2009

Abstract  To understand the evolutionary conservation of the gene expression mechanism and secretion machinery between Antheraea and Bombyx fibroins, we introduced the genomic A. yamamai fibroin gene into the domesticated silkworm, B. mori. The spliced A. yamamai fibroin mRNA appeared only in the posterior region of the silk gland of the transgenic silkworm, suggesting that the functions of the fibroin promoter region and the splicing machinery are conserved between these two species. The A. yamamai fibroin protein was detected in the lumen of the silk gland of the transgenic silkworm, albeit at lower levels compared with the B. mori‐type fibroin. We found a strong degeneration of the posterior region of the silk gland of the transgenic silkworm. As a result, the cocoon shell weight was much lower in the transgenic silkworm than in the non‐transgenic line. These results indicate that the promoter function and splicing machinery are well conserved between A. yamamai and B. mori but that the secretion mechanism of fibroin is diversified between the two.
Response of Solenopsis invicta (Hymenoptera: Formicidae) to potassium oleate water solution
Authors: Chen Jian , Shang Han‐Wu , Jin Xixuan
Published: November 2009

Abstract  In contrast to floating on the surface of distilled water, ants were immediately submerged after being placed in the potassium oleate (PO) water solution, which led to immobilization within minutes. However, some workers survived after being immersed in 0.03% PO water solution at 25°C for up to 640 min. Elevated temperature of the PO water solution is needed to kill ants within a shorter time frame. At 50°C and 0.13% PO concentration, total mortality was achieved with 10‐min immersion for all ants, including brood and adult ants. Soil has a negative effect on the effectiveness of potassium oleate; however, such negative effect can be overcome by increasing either treatment temperature or duration of the treatment. In addition to immobilizing and lethal effect, PO repels ants. PO may have the potential to be incorporated into immersion treatment for the quarantine of imported fire ants to reduce the use of synthetic contact insecticides.
Functional characterization of PGRP‐LC1 of Anopheles gambiae through deletion and RNA interference
Authors: Chen Yang , Ling Erjun , Weng Zhihui
Published: November 2009

Abstract  Peptidoglycan recognition proteins (PGRP) play an important role in innate immunity in insects through the activation of the Imd pathway, which has been shown to be required in the antibacterial response in insects and in the limitation of the number of Plasmodium berghei oocysts developing in mosquito midgut. The LC1 gene of the PRGP family in Anopheles gambiae produces many products through alternative splicing. In this work, we demonstrate that PGRP‐LC1a alone is sufficient to activate the Imd pathway in the A. gambiae L3–5 cell line through a combination of terminal or internal deletions, and RNA interference against endogenous PGRP‐LC products. In the absence of endogenous PGRP‐LC proteins, the integrity of the cytoplasmic domain is necessary for LC1a function, while that of the extracellular domain is not. Moreover, the shorter the extracellular domain, the higher the activity for LC1a. However, the removal of either the cytoplasmic or the extracellular PGRP‐binding domain has little impact on the activity of LC1a in the presence of endogenous PGRP‐LC proteins.