bluuebunny/crossref_metadata_2025 huggingface dataset:
AN EMPIRICAL ANALYSIS OF STOCK MARKET INTEGRATION: COMPARISON STUDY OF SINGAPORE AND MALAYSIA
Authors: YI ZHENG , TAN SWEE-LIANG
Published: July 2009

Using a GARCH (1,1) model, this paper compares the extent to which financial sector liberalization in Singapore and Malaysia each has led to integration of its domestic equity market with external markets. The results show that the level of integration of the domestic markets with the external markets is higher when MSCI regional and global data are used, as compared to when individual country data are used to proxy regional and global markets. Inferences are made about the preferred pace of liberalization in Singapore, as well as, the impact of the Asian financial crisis and capital control measures imposed in Malaysia on financial integration, in the respective countries under study.
RECURSIVE PREFERENCE, MOOD FLUCTUATION AND WELFARE COST OF REDUCED GROWTH
Authors: DONG ZHIYONG , GU QINGYANG , ZHU XIAOMING
Published: July 2009

This paper studies the mood fluctuation of a typical consumer with recursive preference and the welfare cost of reduced growth and business cycle. We estimate the welfare cost using discrete recursive function as well as conduct simulation in order to compare our results with other existing research findings. Our findings are in line with traditional literature whereby the welfare cost of reduced growth is larger than that of business cycle; but our results show that these past measures understate the welfare cost of reduced growth and business cycle.
EXACT ONE-PERIODIC AND TWO-PERIODIC WAVE SOLUTIONS TO HIROTA BILINEAR EQUATIONS IN (2+1) DIMENSIONS
Authors: MA WEN-XIU , ZHOU RUGUANG , GAO LIANG
Published: July 2009

Riemann theta functions are used to construct one-periodic and two-periodic wave solutions to a class of (2+1)-dimensional Hirota bilinear equations. The basis for the involved solution analysis is the Hirota bilinear formulation, and the particular dependence of the equations on independent variables guarantees the existence of one-periodic and two-periodic wave solutions involving an arbitrary purely imaginary Riemann matrix. The resulting theory is applied to two nonlinear equations possessing Hirota bilinear forms: ut + uxxy - 3uuy - 3uxv = 0 and ut + uxxxxy - (5uxxv + 10uxyu - 15u2v)x = 0 where vx = uy, thereby yielding their one-periodic and two-periodic wave solutions describing one-dimensional propagation of waves.
LEVI–CIVITA SPACETIMES IN MULTIDIMENSIONAL THEORIES
Authors: PONCE DE LEON J.
Published: July 2009

We obtain the most general static cylindrically symmetric vacuum solutions of the Einstein field equations in (4 + N) dimensions. Under the assumption of separation of variables, we construct a family of Levi–Civita–Kasner vacuum solutions in (4 + N) dimensions. We discuss the dimensional reduction of the static solutions. Depending on the reduction procedure, they can be interpreted either as a scalar-vacuum generalization of Levi–Civita spacetimes, or as the effective 4D vacuum spacetime outside of an idealized string in braneworld theory.
CASORATIAN SOLUTIONS AND NEW SYMMETRIES OF THE DIFFERENTIAL-DIFFERENCE KADOMTSEV–PETVIASHVILI EQUATION
Authors: ZHANG DA-JUN , JI JIE , SUN XIAN-LONG
Published: July 2009

This paper first discusses the condition in which Casoratian entries satisfy for the differential-difference Kadomtsev–Petviashvili equation. Then from the Casoratian condition we find a transformation under which the differential-difference Kadomtsev–Petviashvili equation is invariant. The transformation, consisting of a combination of Galilean and scalar transformations, provides a single-parameter invariant group for the equation. We further derive the related symmetry, and the symmetry together with other two symmetries form a closed three-dimensional Lie algebra.
MAGNETIC-CONTROLLED NEGATIVE REFRACTION IN FERROMAGNETIC NANOWIRES COMPOSITE
Authors: DA HAI-XIA , WU J. C. , LI Z. Y.
Published: July 2009

Microfabrication of tunable negative refraction materials used in many experimental studies currently relies on the change of the component or the geometrical structure. We theoretically demonstrate magnetically controlled negative permeability in the composite composed of magnetic nanowires (Ni). A magnetic-field-dependent permeability was clearly observed by changing the applied magnetic field, which directly proves the tunable feature of the composite with a small external magnetic field. The simulation results suggest that magnetic nanowires composite can be an alternative route to realizing tunable negative refraction.
A NEW PARAMETER: AN ABACUS FOR OPTIMIZING PV–T HYBRID SOLAR DEVICE FUNCTIONAL MATERIALS USING THE BOUBAKER POLYNOMIALS EXPANSION SCHEME
Authors: FRIDJINE S. , AMLOUK M.
Published: July 2009

In this study, we define a synthetic parameter: optothermal expansivity as a quantitative guide to evaluating and optimizing both the thermal and the optical performance of PV–T functional materials. The definition of this parameter, ψAB(Amlouk–Boubaker parameter), takes into account the thermal diffusivity and the optical effective absorptivity of the material. The values of this parameter, which seems to be a characteristic one, correspond to the total volume that contains a fixed amount of heat per unit time (m3s-1) and can be considered as a 3D velocity of the transmitted heat inside the material.

As the PV–T combined devices need to have simultaneous optical and thermal efficiency, we try to investigate some recently proposed materials (β- SnS2, In2S3, ZnS1-xSex|0 ≤x<0.5and Zn -doped thioindate compounds) using the newly established ψAB/Egabacus.
TRANSIENT AND STEADY-STATE ABSORPTIONS OF A WEAK PROBE FIELD IN A COUPLED DOUBLE QUANTUM-WELL STRUCTURE
Authors: YANG WEN-XING , XU JIN , LEE RAY-KUANG
Published: July 2009

We propose and analyze an efficient scheme for suppressing the absorption of a weak probe field based on intersubband transitions in a four-level asymmetric coupled quantum well (CQW) driven coherently by a probe laser field and a control laser field. We study the steady-state process analytically and numerically, and our results show that the probe absorption can be completely eliminated under the condition of Raman resonance (i.e. two-photon detuning is zero). Besides, we can observe one transparency window without requiring one- or two-photon detuning to exactly vanish. This investigation may provide a possible scheme for EIT in solids by using the CQW.
EMERGING USER INTENTIONS: MATCHING USER QUERIES WITH TOPIC EVOLUTION IN NEWS TEXT STREAMS
Authors: VALENCIA MARIA , LAUTH CODRINA , MENASALVAS ERNESTINA
Published: July 2009

Trend detection analysis from unstructured data poses a huge challenge to current advanced, web-enabled knowledge-based systems (KBS). Consolidated studies in topic and trend detection from text streams have concentrated so far mainly on identifying and visualizing dynamically evolving text patterns. From the knowledge modeling perspective identifying and defining new, relevant features that are able to synchronize the emergent user intentions to the dynamicity of the system's structure is a need. Additionally the advanced KBS have to remain highly sensitive to the content change, marked by evolution of trends in topics extracted from text streams. In this paper, we are describing a three-layered approach called the "user-system-content method" that is helping us to identify the most relevant knowledge mapping features derived from the USER, SYSTEM and CONTENT perspectives into an overall "context model", that will enable the advanced KBS to automatically streamline the query enrichment process in a much more user-centered, dynamical and flexible way. After a general introduction to our three-layered approach, we will describe into detail the necessary process steps for the implementation of our method and will present a case study for its integration on a real multimedia web-content portal using news streams as major source of unstructured information.
COMPARISON OF SETS AND MULTISETS
Authors: HALLEZ AXEL , BRONSELAER ANTOON , DE TRÉ GUY
Published: July 2009

The comparison of sets of objects is a research topic with applications in diverse fields such as computer science, biology and psychology. Since the introduction of the Jaccard index, many techniques have been proposed. This paper aims at extending an existing framework of comparison indices for sets. Firstly, the novel indices account for similarities between elements, rather than identity of elements as is the case for existing techniques. As a result, a richer framework of comparison indices is obtained. The use of fuzzy quantifiers in this framework is shown. Secondly, the machinery for sets is extended to the case of multisets, which results in two classes of comparison indices. The first class considers each element instance as a separate element, while the second class considers groups of elements instances as an atomic entity. The number of instances is then a property of this group, that is taken into account when calculating similarity between element groups.
SOLITON PERTURBATION THEORY FOR DISPERSION-MANAGED OPTICAL FIBERS
Authors: KOHL RUSSELL , MILOVIC DANIELA , ZERRAD ESSAID , BISWAS ANJAN
Published: July 2009

This paper studies the propagation of solitons through optical fibers with dispersion management. The adiabatic variation of the soliton parameters, due to the presence of perturbation terms, is obtained. The dynamics is studied for the case of polarization-preserving fibers, while the types of pulses that are considered here are Gaussian, super-Gaussian and supersech. The perturbation terms that are taken into consideration are both local and nonlocal.
WAVELENGTH CONVERSION OF MULTICHANNEL SPECTRUM-SLICED ASE SIGNALS VIA FOUR-WAVE MIXING IN HIGHLY NONLINEAR DISPERSION-SHIFTED FIBER
Authors: DONG PENG , TIAN YU , XIAO XIAOSHENG , YANG CHANGXI
Published: July 2009

Simultaneous wavelength conversion of multiple spectrum-sliced amplified spontaneous emission channels is achieved experimentally via four-wave mixing (FWM) in highly-nonlinear dispersion-shifted fiber. A theoretical model for FWM between coherent pump and incoherent signals is built based on FWM theory of coherent light. The theoretical result agrees well with the experimental result.
SOLVABILITY OF NEUMANN TYPE NON-HOMOGENEOUS MULTI-POINT BVP FOR SECOND ORDER DIFFERENTIAL EQUATIONS WITH p-LAPLACIAN
Authors: LIU YUJI
Published: July 2009

We consider the following multi-point boundary value problems [Formula: see text] New sufficient conditions to guarantee the existence of at least one solution of the above mentioned BVP are established. Two examples are presented to illustrate the main result.
LARGE-AREA GRAPHENE-BASED FLEXIBLE TRANSPARENT CONDUCTING FILMS
Authors: GÜNEŞ FETHULLAH , HAN GANG HEE , KIM KI KANG , KIM EUN SUNG , CHAE SEUNG JIN , PARK MIN HO , JEONG HAE-KYUNG , LIM SEONG CHU , LEE YOUNG HEE
Published: July 2009

A simple approach by direct synthesis of few-layer graphene sheets and transferring them onto flexible substrate is demonstrated. The hydrogen effect on the D band intensity of Raman spectra for few-layer graphene sheets synthesized by chemical vapor deposition (CVD) on Ni -evaporated silicon substrate is investigated by optimizing the mixing ratio of C 2 H 4/ H 2. While the Ni etchant is used to melt away the squeezed Ni layers between graphene sheet and silicon substrate, the graphene sheet is transferred onto polyethylene terephthalate film by a fishing method. It is found that the condition of graphene transfer strongly relies on the cooling rate of the film during CVD synthesis. The sheet resistance of the film decreases as the film thickness increases. A sheet resistance of 233 Ω/sq is obtained at a transmittance of 62%.
FABRICATION AND CHARACTERIZATION OF FUNCTIONALLY GRADED Ni–Ti MULTILAYER THIN FILMS
Authors: TIAN H. , SCHRYVERS D. , MOHANCHANDRA K. P. , CARMAN G. P. , VAN HUMBEECK J.
Published: July 2009

A functionally graded multilayer Ni – Ti thin film was deposited on a SiO 2/ Si substrate by d.c. sputtering using a ramped heated Ni – Ti alloy target. The stand-alone films were crystallized at 500°C in vacuum better than 10-7 Torr. Transmission electron microscopy micrographs taken along the film cross section show two distinct regions, thin and thick, with weak R and B2 phases, respectively. The film compositions along the thickness were measured and quantified using the standard-less EELSMODEL method. The film deposited during the initial thermal ramp (thin regions) displays an average of 54 at.% Ni while the film deposited at a more elevated target temperature (thick regions) shows about 51 at.% Ni .
Basal glacier ice and massive ground ice: different scientists, same science?
Authors: Waller Richard I. , Murton Julian B. , Knight Peter G.
Published: July 2009

Whilst glaciologists and permafrost researchers investigate ice bodies using similar techniques, there has been surprisingly little collaboration between the two communities. This paper examines the potential benefits of interdisciplinary research into the formation of basal ice beneath glaciers and the origin of massive ice in glaciated permafrost regions. Active collaboration in these areas has already improved our understanding of the formation of basal ice beneath cold-based glaciers, the critical role played by basal freezing in controlling the dynamic behaviour of stagnating ice streams and the significance of glacier–permafrost interactions at the margins of Pleistocene ice sheets. However, in order to promote future collaboration certain obstacles need to be overcome. The contrasting ice-classification schemes employed by glaciologists and permafrost scientists, for example, need to be unified in order to allow detailed comparisons of ice-rich sequences in both environments. This could, in turn, enable exciting research advances, most notably by facilitating the identification of preserved remnants of Pleistocene ice sheets within permafrost regions that provide a potentially invaluable and currently largely untapped source of palaeoglaciological information.
Role of the atypical protein kinase Cζ in regulation of 5′-AMP-activated protein kinase in cardiac and skeletal muscle
Authors: Ussher John R. , Jaswal Jagdip S. , Wagg Cory S. , Armstrong Heather E. , Lopaschuk David G. , Keung Wendy , Lopaschuk Gary D.
Published: July 2009

During metabolic stress, phosphorylation and activation of 5′-AMP-activated protein kinase (AMPK) becomes a major regulator of cellular energy metabolism in heart and skeletal muscle. Despite this, the upstream regulation of AMPK in both heart and muscle is poorly understood. Recent work has implicated the atypical protein kinase Cζ (PKCζ) as a regulator of AMPK in endothelial cells via phosphorylation of LKB1, an upstream AMPK kinase (AMPKK). Our goal was to determine the potential role PKCζ plays in regulating AMPK in cardiac and skeletal muscle. Cultures of H9c2 myocytes (cardiac) and C2C12 myotubes (skeletal muscle) were pretreated with a selective PKCζ pseudosubstrate peptide inhibitor and treated with various AMPK activating agents to determine whether PKCζ regulates AMPK. PKCζ activity was also examined in isolated working rat hearts subjected to ischemia. We show that PKCζ is not involved in regulating threonine 172 AMPK phosphorylation induced by metformin or phenformin in either cardiac or skeletal muscle cells but is involved in 5-aminoimidazole-4-carboxamine-1-β-d-ribofuranoside (AICAR)-induced AMPK phosphorylation in cardiac muscle cells. Activation of PKCζ with high palmitate concentrations is also insufficient to increase AMPK phosphorylation. Furthermore, we show that the ischemia-induced activation of AMPK is not accompanied by increased PKCζ activity. Finally, we show that PKCζ may actually be a downstream target of AMPK in skeletal muscle, since adenoviral expression of a dominant-negative mutant of AMPK prevented metformin- and AICAR-induced phosphorylation of PKCζ. We conclude that PKCζ plays a very minor role in the regulation of AMPK in cardiac and skeletal muscle and may actually be a downstream target of AMPK in skeletal muscle.
Enterostatin deficiency increases serum cholesterol but does not influence growth and food intake in mice
Authors: Miller Rita , D'Agostino Dymphna , Erlanson-Albertsson Charlotte , Lowe Mark E.
Published: July 2009

A pentapeptide released from procolipase, enterostatin, selectively attenuates dietary fat intake when administered peripherally or centrally. Enterostatin may act through the afferent vagus nerve and in the hypothalamus and amygdala, primarily in the central nucleus of the amygdala. To investigate the physiological role of endogenous enterostatin, we created an enterostatin-deficient, colipase-sufficient ( Ent−/−) mouse. Ent−/− mice are viable, normally active, and fertile. They exhibit normal growth on low-fat and high-fat diets. Furthermore, Ent−/− mice develop diet-induced obesity, as do Ent+/+ mice, and have normal responses to a two-macronutrient choice diet and to a switch from a high-fat to a low-fat diet. Levels of total serum ( P = 0.004) and non-HDL ( P ≤ 0.001) cholesterol were higher and levels of HDL cholesterol ( P = 0.01) were lower in Ent−/− than in wild-type mice. To determine whether enterostatin contributed to the decreased survival or whether colipase deficiency was the sole contributor, we administered enterostatin to procolipase-deficient ( Clps−/−) mouse pups. Enterostatin significantly improved survival ( P ≤ 0.001). Our results demonstrate that enterostatin is not critically required to regulate food intake or growth, suggesting that other pathways may compensate for the loss of enterostatin. Enterostatin has developmental effects on survival of newborns and alters cholesterol metabolism.
Cell cycle actions of parathyroid hormone-related protein in non-small cell lung carcinoma
Authors: Hastings Randolph H. , Montgrain Philippe R. , Quintana Rick , Rascon Yvette , Deftos Leonard J. , Healy Erin
Published: July 2009

Parathyroid hormone-related protein (PTHrP), a paraneoplastic protein expressed by two-thirds of human non-small cell lung cancers, has been reported to slow progression of lung carcinomas in mouse models and to lengthen survival of patients with lung cancer. This study investigated the effects of ectopic expression of PTHrP on proliferation and cell cycle progression of two human lung adenocarcinoma cell lines that are normally PTHrP negative. Stable transfection with PTHrP decreased H1944 cell DNA synthesis, measured by thymidine incorporation, bromodeoxyuridine uptake, and MTT proliferation assay. A substantial fraction of PTHrP-positive cells was arrested in or slowly progressing through G1. Cyclin D2 and cyclin A2 protein levels were 60–70% lower in PTHrP-expressing cells compared with control cells ( P < 0.05, N = 3 independent clones per group), while expression of p27Kip1, a cyclin-dependent kinase inhibitor, was increased by 35 ± 9% (mean ± SE, P < 0.05) in the presence of PTHrP. Expression of other cyclins, including cyclins D1 and D3, and cyclin-dependent kinases was unaffected by PTHrP. PTHrP did not alter the phosphorylation state of Rb, but decreased cyclin-dependent kinase (CDK) 2-cyclin A2 complex formation. Ectopic expression of PTHrP stimulated ERK phosphorylation. In MV522 cells, PTHrP had similar effects on DNA synthesis, cyclin A2 expression, pRb levels, CDK2-cyclin A2 association, and ERK activation. In summary, PTHrP appears to slow progression of lung cancer cells into S phase, possibly by decreasing activation of CDK2. Slower cancer cell proliferation could contribute to slower tumor progression and increased survival of patients with PTHrP-positive lung cancer.
Three-dimensional alignment of the aggregated myocytes in the normal and hypertrophic murine heart
Authors: Schmitt Boris , Fedarava Katsiaryna , Falkenberg Jan , Rothaus Kai , Bodhey Narendra K. , Reischauer Carolin , Kozerke Sebastian , Schnackenburg Bernhard , Westermann Dirk , Lunkenheimer Paul P. , Anderson Robert H. , Berger Felix , Kuehne Titus
Published: July 2009

Several observations suggest that the transmission of myocardial forces is influenced in part by the spatial arrangement of the myocytes aggregated together within ventricular mass. Our aim was to assess, using diffusion tensor magnetic resonance imaging (DT-MRI), any differences in the three-dimensional arrangement of these myocytes in the normal heart compared with the hypertrophic murine myocardium. We induced ventricular hypertrophy in seven mice by infusion of angiotensin II through a subcutaneous pump, with seven other mice serving as controls. DT-MRI of explanted hearts was performed at 3.0 Tesla. We used the primary eigenvector in each voxel to determine the three-dimensional orientation of aggregated myocytes in respect to their helical angles and their transmural courses (intruding angles). Compared with controls, the hypertrophic hearts showed significant increases in myocardial mass and the outer radius of the left ventricular chamber ( P < 0.05). In both groups, a significant change was noted from positive intruding angles at the base to negative angles at the ventricular apex ( P < 0.01). Compared with controls, the hypertrophied hearts had significantly larger intruding angles of the aggregated myocytes, notably in the apical and basal slices ( P < 0.001). In both groups, the helical angles were greatest in midventricular sections, albeit with significantly smaller angles in the mice with hypertrophied myocardium ( P < 0.01). The use of DT-MRI revealed significant differences in helix and intruding angles of the myocytes in the mice with hypertrophied myocardium.
Cardiovascular Disease and Psychiatric Comorbidity: The Potential Role of Perseverative Cognition
Authors: Larsen Britta A. , Christenfeld Nicholas J. S.
Published: July 2009

The high comorbidity between psychiatric disorders and cardiovascular disease has received increasing attention, yet little is known about the processes linking the two. One plausible contributing mechanism is the tendency of those with psychiatric disorders to ruminate on stressful events. This phenomenon, sometimes called perseverative cognition, can extend the psychological and physiological effects of stress, which could contribute to cardiovascular disease etiology. In this paper, we discuss the potential role of perseverative cognition in mediating the relationship between psychiatric illness and cardiovascular disease. Rumination can delay physiological recovery from acute stress, which in turn has been found to predict future cardiovascular health. This delayed recovery could act as a mechanism in the longitudinal link between worry and cardiovascular health. The cognitive inflexibility that characterizes mood and anxiety disorders may then contribute to disease not by producing greater reactivity, but instead through extending activation, increasing the risks for cardiovascular damage.
Low Concentrations of Diindolylmethane, a Metabolite of Indole-3-Carbinol, Protect against Oxidative Stress in a BRCA1-Dependent Manner
Authors: Fan Saijun , Meng Qinghui , Saha Tapas , Sarkar Fazlul H. , Rosen Eliot M.
Published: July 2009

The indole-3-carbinol (I3C) metabolite 3,3′-diindolylmethane (DIM) is a proposed cancer prevention agent for various tumor types, including breast cancer. Here, we show that DIM up-regulates expression of the tumor suppressor protein BRCA1 in carcinoma and normal cell types. Up-regulation of BRCA1 was dose and time dependent, and it was observed at physiologically relevant micromolar and submicromolar DIM concentrations when cells were exposed for 72 hours. Treatment with the parent compound (I3C) or DIM (1 μmol/L) protected against cell killing due to H2O2 and other oxidants, and the protection was abrogated by knockdown of BRCA1. DIM stimulated signaling by the antioxidant transcription factor NFE2L2 (NRF2) through the antioxidant response element in a BRCA1-dependent manner. We further showed that DIM rapidly stimulated phosphorylation of BRCA1 on Ser 1387 and Ser 1524 and that these phosphorylations are required for protection against oxidative stress. DIM-induced phosphorylation of BRCA1 on Ser 1387 was dependent on ataxia-telangiectasia mutated. Finally, in our assay systems, H2O2-induced cell death was not due to apoptosis. However, a significant component of cell death was attributable to autophagy, and both DIM and BRCA1 inhibited H2O2-induced autophagy. Our findings suggest that low concentrations of DIM protect cells against oxidative stress via the tumor suppressor BRCA1 by several distinct mechanisms. [Cancer Res 2009;69(15):6083–91]
Identification of Las2, a Major Modifier Gene Affecting the Pas1 Mouse Lung Tumor Susceptibility Locus
Authors: Liu Peng-Yuan , Vikis Haris , James Michael , Lu Yan , Wang Dao-Long , Liu Hong-Bo , Wen Wei-Dong , Wang Yian , You Ming
Published: July 2009

Lung cancer is the leading cause of cancer death worldwide. Here, we describe a genome-wide association study of chemically induced lung tumorigenesis on 593 mice from 21 inbred strains using 115,904 genotyped and 1,952,918 imputed single nucleotide polymorphisms (SNPs). Using a genetic background–controlled genome search, we identified a novel lung tumor susceptibility gene Las2 (Lung adenoma susceptibility 2) on distal chromosome 18. Las2 showed strong association with resistance to tumor induction (rs30245983; P = 1.87 × 10−9) as well as epistatic interactions (P = 1.71 × 10−3) with the pulmonary adenoma susceptibility 1 locus, a major locus affecting mouse lung tumor development (rs13459098, P = 5.64 × 10−27). Sequencing analysis revealed four nonsynonymous SNPs and two insertions/deletions in the susceptible allele of Las2, resulting in the loss of tumor suppressor activities in both cell colony formation and nude mouse tumorigenicity assays. Deletion of LAS2 was observed in ∼40% of human lung adenocarcinomas, implying that loss of function of LAS2 may be a key step for lung tumorigenesis. [Cancer Res 2009;69(15):6290–8]
A Spontaneous Acinar Cell Carcinoma Model for Monitoring Progression of Pancreatic Lesions and Response to Treatment Through Noninvasive Bioluminescence Imaging
Authors: Zhang Ning , Lyons Scott , Lim Ed , Lassota Peter
Published: July 2009

Purpose: We have generated an EL1-luc/TAg transgenic mouse model that develops spontaneous and bioluminescent acinar cell carcinomas. We applied this model to noninvasively monitor tumor development and drug response.

Experimental Design: EL1-luc/TAg transgenic mice of 11 weeks of age were treated with rapamycin (5 mg/kg, i.p.) or vehicle for 6 to 12 weeks. Tumor development was monitored through bioluminescence imaging and necropsy at the study end point.

Results: EL1-luc/TAg transgenic mice showed pancreas-specific bioluminescence signal before tumor progression and produced increasing light emission from the onset of the pancreatic acinar cell carcinomas. The latency of tumor development ranged from 10 to >20 weeks of age in these mice. Progression of the primary acinar cell carcinoma was accompanied by emergence of metastatic lesions in the abdominal organs, including liver and gastrointestinal fat tissues. Rapamycin treatment suppressed tumor development.

Conclusions: The EL1-luc/TAg mouse provides a noninvasive approach for monitoring spontaneous acinar cell carcinoma development and comprises a convenient tool for the evaluation of novel therapeutics against pancreatic cancers. Tumor growth suppression through inhibition of the mammalian target of rapamycin pathway further validates this model as clinically relevant.
EPOX Inhibits Angiogenesis by Degradation of Mcl-1 through ERK Inactivation
Authors: Sun Hui-Lung , Tsai An-Chi , Pan Shiow-Lin , Ding Qingqing , Yamaguchi Hirohito , Lin Chun-Nan , Hung Mien-Chie , Teng Che-Ming
Published: July 2009

Purpose: Antiangiogenic therapy is considered as an effective strategy for controlling the growth and metastasis of tumors. Among a myriad of biological activities described for xanthone derivatives, the anticancer activity is quite remarkable, but the molecular mechanism is not clearly resolved. In the present study, we investigated the antiangiogenic mechanism of 3,6-di(2,3-epoxypropoxy)xanthone (EPOX), a novel Mcl-1 targeting drug.

Experimental Design: To evaluate the antiangiogenic activity of EPOX, we did cell viability, cell cycle, tube formation assay in vitro, and Matrigel plug assay in vivo. To evaluate the effect of EPOX on the endothelial signaling pathway, we did immunoblotting, immunoprecipitation, and immunofluorescence analysis. Intracellular glutathione levels were determined with the use of monochlorobimane, a glutathione-specific probe.

Results: EPOX induced endothelial cell apoptosis in association with proteasome-dependent Mcl-1 degradation. Down-regulation of Mcl-1 resulted in an increase in Mcl-1–free Bim, activation of Bax, and then signaling of mitochondria-mediated apoptosis. Additionally, glutathione depletion and extracellular signal-regulated kinase (ERK) inactivation was observed in EPOX-treated cells. Glutathione supplementation reversed the inhibitory effects of EPOX on ERK, which increases the phosphorylation of Mcl-1 at T163. Overexpression of mitogen-activated protein/ERK kinase (MEK) partially reversed the effect of EPOX on Mcl-1 dephosphorylation, ubiquitination, and degradation, further implicating ERK in the regulation of Mcl-1 stability.

Conclusions: This study provides evidence that EPOX induces glutathione depletion, ERK inactivation, and Mcl-1 degradation on endothelial cells, which leads to inhibition of angiogenesis. Our results suggest that EPOX is a novel antiangiogenic agent, making it a promising lead compound for further development in the treatment of angiogenesis-related pathologies.
Cancer Pharmacoethnicity: Ethnic Differences in Susceptibility to the Effects of Chemotherapy
Authors: O'Donnell Peter H. , Dolan M. Eileen
Published: July 2009

A long-term goal of pharmacogenomics research is the design of individualized therapy based on the genomic sequence of the patient, in order to maximize response and minimize adverse drug reactions. Pharmacoethnicity, or ethnic diversity in drug response or toxicity, is becoming increasingly recognized as an important factor accounting for interindividual variation in anticancer drug responsiveness. Although pharmacoethnicity is determined by genetic and nongenetic factors, there is rapidly accumulating clinical evidence about ethnic differences in the frequencies of polymorphisms within many of the important cancer drug-related genes. This article reviews the current clinical evidence for ethnic differences in anticancer drug disposition and sensitivity while highlighting the challenges, and potential solutions, to acquiring such knowledge. The discovery of “ethnic-specific genetic signatures,” representing unique sets of drug susceptibility-governing polymorphisms, may be the outcome of such work. Ultimately, such understanding will further the lofty goal of individualization of chemotherapy based on a person's unique genetic make-up to improve the tolerability and effectiveness of chemotherapy for all patients.
Transcriptional Repression and Inhibition of Nuclear Translocation of Androgen Receptor by Diallyl Trisulfide in Human Prostate Cancer Cells
Authors: Stan Silvia D. , Singh Shivendra V.
Published: July 2009

Purpose: The present study was undertaken to determine the effect of diallyl trisulfide (DATS), a promising cancer chemopreventive constituent of garlic, on androgen receptor (AR) protein expression and function using prostate cancer cells.

Experimental Design: The protein levels of AR and prostate-specific antigen (PSA) were determined by immunoblotting. The effect of DATS treatment on AR mRNA level and AR promoter activity was determined by quantitative reverse transcription-PCR and luciferase reporter assay, respectively. Expression of AR protein in poorly differentiated carcinoma and normal prostate of transgenic adenocarcinoma of mouse prostate (TRAMP) mice was determined by immunohistochemistry. Confocal microscopy was done to determine nuclear translocation of AR. Cell viability was determined by trypan blue dye exclusion assay.

Results: Exposure of prostate cancer cells (LNCaP, C4-2, and TRAMP-C1) to DATS resulted in a concentration-dependent decrease in protein level of AR, which was accompanied by suppression of intracellular and secreted levels of PSA. Structure-activity studies revealed critical roles for allyl groups and the oligosulfide chain length in DATS-mediated down-modulation of AR protein. Quantitative reverse transcription-PCR showed a dose-dependent decrease in AR mRNA level, which correlated with inhibition of AR promoter activity. DATS treatment inhibited synthetic androgen (R1881)-stimulated nuclear translocation of AR in LNCaP/C4-2 cells and proliferation of LNCaP cells. Oral gavage of 2 mg/day DATS (three times per week for 13 weeks) markedly suppressed AR protein level in poorly differentiated prostate cancer in TRAMP mice.

Conclusion: The present study shows, for the first time, that DATS treatment suppresses AR function in prostate cancer cells.
High-Dose Esomeprazole for Treatment of Symptomatic Refractory Gastroesophageal Reflux Disease – A Prospective pH-Metry/Impedance-Controlled Study
Authors: Bajbouj Monther , Becker Valentin , Phillip Veit , Wilhelm Dirk , Schmid Roland M. , Meining Alexander
Published: July 2009

Background/Aims: Combined pH-metry/multichannel intraluminal impedance (pH/MII) measurement enables to measure gastroesophageal reflux despite ongoing proton pump inhibitor therapy. The aim of our study was to evaluate the influence of an escalating medical anti-reflux therapy with 40 mg esomeprazole, 80 mg esomeprazole and 80 mg esomeprazole plus baclofen for the treatment of refractory pathological reflux as determined by pH/MII. Methods: Symptomatic patients under 40 mg esomeprazole were screened by pH/MII. Patients with normal values in pH/MII were excluded; all others received 2 × 40 mg esomeprazole for another 4 weeks. Thereafter, the treatment effect was controlled by pH/MII. In the case of persistent pathological reflux, therapy was further escalated by adding baclofen and controlled after 3 months by pH/MII. Results: 45/138 (32.6%) patients showed pathological pH/MII despite ongoing therapy with 40 mg esomeprazole. In these, a significant reduction in liquid/mixed reflux events was observed after administering 2 × 40 mg (mean: 118.3 vs. mean: 66.6; p < 0.001), and pH/MII turned to normal in 32/45 (71.1%). Baclofen was additionally administered to 7/13 patients, which did not lead to a remarkable reduction in reflux events. Conclusion: In patients with abnormal pH/MII and persistent symptoms under 40 mg esomeprazole, we observed a significant reduction in liquid/mixed reflux events after increasing proton pump inhibitor dose up to 80 mg esomeprazole. Further escalation of therapy with baclofen has shown inconclusive results.
Effect of Music Therapy on Anxiety and Depression in Patients with Alzheimer’s Type Dementia: Randomised, Controlled Study
Authors: Guétin S. , Portet F. , Picot M.C. , Pommié C. , Messaoudi M. , Djabelkir L. , Olsen A.L. , Cano M.M. , Lecourt E. , Touchon J.
Published: July 2009

Background/Aims: Numerous studies have indicated the value of music therapy in the management of patients with Alzheimer’s disease. A recent pilot study demonstrated the feasibility and usefulness of a new music therapy technique. The aim of this controlled, randomised study was to assess the effects of this new music therapy technique on anxiety and depression in patients with mild to moderate Alzheimer-type dementia. Methods: This was a single-centre, comparative, controlled, randomised study, with blinded assessment of its results. The duration of follow-up was 24 weeks. The treated group (n = 15) participated in weekly sessions of individual, receptive music therapy. The musical style of the session was chosen by the patient. The validated ‘U’ technique was employed. The control group (n = 15) participated under the same conditions in reading sessions. The principal endpoint, measured at weeks 1, 4, 8, 16 and 24, was the level of anxiety (Hamilton Scale). Changes in the depression score (Geriatric Depression Scale) were also analyzed as a secondary endpoint. Results: Significant improvements in anxiety (p < 0.01) and depression (p < 0.01) were observed in the music therapy group as from week 4 and until week 16. The effect of music therapy was sustained for up to 8 weeks after the discontinuation of sessions between weeks 16 and 24 (p < 0.01). Conclusion: These results confirm the valuable effect of music therapy on anxiety and depression in patients with mild to moderate Alzheimer’s disease. This new music therapy technique is simple to implement and can easily be integrated in a multidisciplinary programme for the management of Alzheimer’s disease.
Association between Small Deep Cerebellar Ischemic Lesion and Small-Vessel Disease
Authors: Park Kwang-Yeol , Chung Pil-Wook , Kim Yong Bum , Moon Heui-Soo , Suh Bum-Chun , Won Yu Sam
Published: July 2009

Background: Pathologic investigations showed that lacunar infarction could develop in the deep cerebellar region. However, the etiology of small deep cerebellar ischemic lesions (SDCI) has not been adequately studied. The aim of this study was to investigate the relationship between SDCI and small-vessel disease. Methods: We studied 100 consecutive patients who had both (1) acute ischemic stroke (index stroke) confirmed by diffusion-weighted MRI and (2) evidence of a chronic small cerebellar ischemic lesion (<15 mm). Small-vessel-related MRI findings, risk factors and subtype of index stroke were compared between the patients with SDCI and those with small cortical cerebellar ischemic lesions (SCCI). Results: Eighty patients had SCCI, and 20 patients had SDCI. Cardioembolic sources (38.8 vs. 5%, p = 0.003) and vertebrobasilar artery stenosis (61.3 vs. 35%, p = 0.034) were more frequent in patients with SCCI. In a multivariate model including traditional risk factors, patients with SDCI had significantly more lacunar infarcts (odds ratio, 1.18; 95% confidence interval, 1.02–1.37) and cerebral microbleeds (odds ratio, 10.92; 95% confidence interval, 2.16–55.32) than those with SCCI. Patients with SDCI frequently had the small-artery disease subtype of index stroke (odds ratio, 5.84; 95% confidence interval, 1.71–19.9). Conclusions: The results suggest that SDCI are frequently associated with small-vessel disease.
Characterization of Bacteria, Clostridia and Bacteroides in Faeces of Vegetarians Using qPCR and PCR-DGGE Fingerprinting
Authors: Liszt Kathrin , Zwielehner Jutta , Handschur Michael , Hippe Berit , Thaler Roman , Haslberger Alexander G.
Published: July 2009

Background/Aims: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. Methods: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. Results: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 ± 17.00%; 36.64 ± 14.22%) and higher abundance of Bacteroides (23.93 ± 10.35%; 21.26 ± 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. Conclusions: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks.
Reproducibility of Measures of Visit-to-Visit Variability in Blood Pressure after Transient Ischaemic Attack or Minor Stroke
Authors: Howard S.C. , Rothwell P.M.
Published: July 2009

Background: In certain patients in routine practice, blood pressure (BP) measurements differ substantially from week to week or month to month. Although often assumed to be random, such variability could provide information on underlying pathology or prognosis. In order to be informative, however, visit-to-visit BP variability would have to be neither random (i.e. it should be reproducible over time within individuals) nor artefactual (i.e. it should not be an artefact of the method/timing of measurement, for example). Methods: We quantified visit-to-visit variability in BP and explored potential confounding factors by analysing repeat measurements obtained every few months during follow-up in two large trials in patients with a transient ischaemic attack (TIA) or minor ischaemic stroke: the UK-TIA Aspirin Trial (effect of aspirin, effect of season and day of the week of measurement) and the European Carotid Surgery Trial (ECST – effect of carotid endarterectomy). By comparing different periods of follow-up, we also determined the reproducibilities of mean and several different measures of variability for both systolic (SBP) and diastolic BP (DBP). Results: The mean absolute difference between adjacent SBP readings was 14.7 mm Hg in the UK-TIA Trial and 16.0 mm Hg in ECST. Visit-to-visit variability in both SBP and DBP were independent of the potentially confounding factors studied, but reproducibility of all the variability measures was statistically significantly greater than zero. Reproducibility (intraclass correlation) of standard deviation of SBP was 0.32 (p < 0.0001) in the UK-TIA Trial and 0.18 (p = 0.0007) in ECST. Consequently, classification of patients with high (top quintile) or low (bottom quintile) variability was consistent over time (observed/expected = 2.21, 95% confidence interval 1.71–2.85, p < 0.0001, and 1.65, 1.23–2.21, p = 0.0007, respectively). Reproducibility increased with the number of measurements used to calculate variability, and was independent of any correlation with mean BP. Conclusions: Visit-to-visit variability in BP in these populations was reproducible, independently of any correlation with mean BP, demonstrating that visit-to-visit intra-individual BP variability is not random.
Current Management and Risk of Recurrent Stroke in Cerebrovascular Patients with Right-to-Left Cardiac Shunt
Authors: Weimar C. , Holle D.N. , Benemann J. , Schmid E. , Schminke U. , Haberl R.L. , Diener H.-C. , Goertler M.
Published: July 2009

Background: Right-to-left cardiac shunt (RLS) is considered a risk factor for stroke, especially in patients aged <55 years. We aimed to investigate the current management and prognosis in consecutive patients with RLS and otherwise cryptogenic cerebrovascular events. Methods: In total, 1,126 patients with cryptogenic stroke or TIA were included from 17 German neurology departments. During a mean follow-up of 28.4 months, we assessed current antithrombotic medication, percutaneous device closure (PDC) and recurrent cerebrovascular events in 899 patients (79.8%). Stroke recurrence was compared between 548 patients without RLS and 351 patients with RLS under various prevention regimens. Results: RLS was detected in 35.9% of cryptogenic cerebrovascular patients, but could not be evaluated as an independent predictor for recurrent stroke (adjusted HR 1.6, 95% CI: 0.9–2.7). In RLS-positive patients, the Kaplan-Meier estimate for stroke during the first year was 4.1% (95% CI: 1.9–6.3%) and 1.7% (95% CI: 0.9–2.4%) per year thereafter. At the last follow-up before recurrent stroke or end of study, 117 RLS-positive patients (33.3%) had received a PDC, 154 (43.9%) were receiving antiplatelets, 63 (17.9%) received anticoagulation, and 17 (4.8%) received none of the above. No association with recurrent stroke was found for the secondary preventive regime. Conclusion: Our multicenter hospital-based cohort study confirmed low recurrent event rates in RLS patients with otherwise cryptogenic stroke or TIA, as well as a great heterogeneity of current management. Despite the lack of scientific evidence, a substantial number of RLS-positive patients underwent PDC for secondary stroke prevention.
Good Response to Paclitaxel Predicts High Rates of Pathologic Complete Response for Breast Cancer Patients Treated Preoperatively with Paclitaxel Followed by 5-Fluorouracil, Epirubicin and Cyclophosphamide
Authors: Kim Seung Jin , Taguchi Tetsuya , Shimazu Kenzo , Tanji Yoshio , Tamaki Yasuhiro , Noguchi Shinzaburo
Published: July 2009

Objective: Predictors of pathologic complete response (pCR) to neoadjuvant chemotherapy for breast cancers have been studied extensively. Here, we focused on reduction rate after paclitaxel administration for prediction of pCR to paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). Methods: This study included 115 patients with tumors ≥3.0 cm or with node-positive disease who were treated preoperatively with paclitaxel (80 mg/m2, once a week, 12 cycles) followed by FEC (500/75/500 mg/m2, every three weeks, 4 cycles). Reduction rate was measured with magnetic resonance imaging. Results: Tumor size (≤5.0 cm) (p = 0.014), estrogen receptor (ER) negativity (p = 0.013), and human epidermal growth factor receptor 2 positivity (p = 0.020), but not histologic type, histologic grade, or progesterone receptor, were significantly associated with pCR, while association of reduction rate ≥80% was highly significant (p = 0.0003). Multivariate analysis identified negative ER (p = 0.022) and reduction rate (p = 0.003) as independent predictors of pCR. Finally, patients with reduction rate ≥80% showed a significantly higher favorable outcome (p = 0.014) than others. Conclusions: Good response (reduction rate ≥80%) to paclitaxel seems to be a clinically useful predictor of pCR as well as a favorable prognosticator for patients treated preoperatively with paclitaxel followed by FEC.
Cognitive Therapy versus Rogerian Supportive Therapy in Borderline Personality Disorder
Authors: Cottraux Jean , Note Ivan Druon , Boutitie Florent , Milliery Maud , Genouihlac Virginie , Yao Sai Nan , Note Brigitte , Mollard Evelyne , Bonasse Françoise , Gaillard Ségolène , Djamoussian Diane , de Mey Guillard Chantal , Culem Alain , Gueyffier François
Published: July 2009

Background: To date, there have been no studies comparing cognitive therapy (CT) with Rogerian supportive therapy (RST) in borderline personality disorder. Method: Sixty-five DSM-IV borderline personality disorder outpatients were recruited at 2 centres: Lyon and Marseille. Thirty-three patients were randomly allocated to CT and 32 to RST. The therapists were the same in both groups. Both treatments shared the same duration (1 year) and amount of therapy. Assessment by independent evaluators utilised the Clinical Global Impression (CGI) Scale, the Hamilton Depression Scale, Beck Depression Inventory, Beck Anxiety Inventory, Hopelessness Scale, Young Schema Questionnaire II, Eysenck Impulsivity Venturesomeness Empathy (IVE) Inventory, a self-harming behaviours checklist and scales measuring quality of life and the therapeutic relationship. The response criterion was a score of 3 or less on the CGI, associated with a Hopelessness Scale score of <8. Results: No patient committed suicide during the trial. Fifty-one patients were evaluated at week 24, 38 at week 52 and 21 at week 104. Cognitive therapy retained the patients in therapy for a longer time. The response criterion found no significant between-group differences at any measurement point in the completers. However, at week 24, CT was better than RST on the Hopelessness Scale, IVE scale and regarding the therapeutic relationship. At week 104, the CGI improvement (patient and evaluator) was significantly better in CT than in RST. High baseline depression and impulsivity predicted dropouts. Conclusions: CT retained the patients in therapy longer, showed earlier positive effects on hopelessness and impulsivity, and demonstrated better long-term outcomes on global measures of improvement.