bluuebunny/crossref_metadata_2025 huggingface dataset:
Dewey's Conception of Being and Philosophical Reflection
Authors: Gotshalk Richard
Published: June 2010

In the following pages I should like critically to consider certain aspects of John Dewey's thought as set forth for the most part in Experience and Nature. In particular, I should like to discuss the conceptions of being and of philosophieal reflection which underlie his delineation of human agency as located in nature and as essentially characterized by reference to the problematic. I select these ideas both because they concern something fundamental philosophieally and because one can see in Dewey's development of them both the strength and weakness of his philosophieal reflection.
The Power of Negative Thinking
Authors: Keenan Brian
Published: June 2010

Before undertaking an examination of the issues current in social criticism, it is necessary to settle upon the method which ought to be common to the several social sciences. For if the adoption of a particular method results in unconscious acceptance of features of the society under critical examination, then clearly any such putative critique is in fact futile. In this paper I examine some of Marcuse's largely negative comments regarding the method currently employed in the social sciences. I am not concerned to arrive at a complete view as to the appropriate method, but rather to expose some questions that need to be answered if any such view is to be formulated.
Peut-on et doit-on fonder la morale?
Authors: Carnois Bernard
Published: June 2010

Que la tâche de fonder la morale soit particulièrement ardue, nul n'en doute, et la diversité des positions philosophiques en ce domaine nous incline à souscrire à la formule célèbre de Schopenhauer: « Prêcher la morale est chose aisée, la fonder chose difficile.» Tout penseur qui forme le dessein de fonder la morale est done en droit de se demander si un tel problème ne passe pas l'entendement humain et s'il sera jamais possible à l'homme de le résoudre. « Quel est le fondement de la morale ? », voilà une question qui semble s'imposer tout naturellement à notre réflexion, dût-elle par ailleurs demeurer sans réponse. Et pourtant, n'y a-t-il pas lieu de mettre en question la question elle-même et de s'interroger sur sa légitimité? Si une telle interrogation paraît, à première vue, insolite, c'est sans doute parce que, lorsque nous parlons de «fonder la morale», notre pensée s'oriente d'emblée vers la recherche du fondement (Grund), sans que l'on songe à mettre en doute le « bien-fondé » de l'acte même de fonder (Grundlegung). C'est précisément pour souligner notre intention de ne point éluder une question aussi radicale que nous avons formulé le thème de notre réflexion de la manière suivante: « Peut-on et doit-on fonder la morale ? ».
Relative impact of α-tocopherol, copper and fatty acid composition on the occurrence of oxidized milk flavour
Authors: Juhlin Jessica , Fikse Freddy , Lundén Anne , Pickova Jana , Agenäs Sigrid
Published: June 2010

The oxidative process in milk fat, resulting in spontaneous oxidized off-flavour (SOF), is commonly assumed to depend on contents of pro- and antioxidants in milk and availability of fatty acids acting as their substrate. An important antioxidant in milk is α-tocopherol whereas the most potent prooxidant is the metal ion copper. The separate effects of α-tocopherol, copper, and milk fatty acid profile, and their combined effect on SOF development were examined in milk from 44 multiparous cows fed different roughage types and different amounts of dietary, unsaturated fat. A clear association between concentrations of copper and poly-unsaturated fatty acids in milk and the risk for developing SOF was found. Heritability estimates suggest that occurrence of SOF is partly under genetic control which indicates that milk quality may be compromised if breeding bulls are selected that carry genotypes predisposing for milk prone to develop SOF.
Energy Issues in the Context of the Regime Transition of Post-Soviet Eurasia: National and International Dimension
Authors: Obydenkova Anastassia
Published: June 2010

In political science, democracy is generally associated with high levels of economic development. However, some scholars note that this is true only as long as economic development is not based on possession of rich energy resources. Many resource-rich states are nondemocratic regimes. This is sometimes called the “resource curse.” This means that “natural resource abundance may stimulate rent-seeking behavior that, together with highly concentrated bureaucratic power, induces corruption in the economy and hence lowers the quality of institutions.” It also means that “resource wealth itself may harm a country's prospects for development” and that “oil and mineral wealth tends to make states less democratic.”
European Court of Justice. The Legal Basis of Internal Market Measures With a Security Dimension. Comment on Case C-301/06 of 10/02/2009, Ireland v. Parliament/Council, nyr
Authors: Poli Sara
Published: June 2010

Introduction

Each time users connect to the internet or make a phone call, they leave ‘digital fingerprints’ which may turn out to be useful for identifying people involved in a crime or an act of terrorism. This is why there is great interest by law enforcement authorities in gaining access to traffic and location data, relying on the forced co-operation of telecommunication and internet providers. However, the effectiveness of compelling these service providers to retain such data for the purpose of fighting crime has been questioned. Moreover, data retention obligations interfere with the right to privacy of individuals, as protected by Article 8 European Convention of Human Rights (ECHR); therefore, they may be imposed only for a legitimate objective, i.e. to protect citizens' safety, and in full respect of the principle of proportionality.
Joanne Simpson (1923–2010)
Authors: Garstang Michael
Published: June 2010

Joanne Gerould Simpson died at George Washington University Hospital, Washington, D.C., on 4 March 2010, just a few weeks short of her 87th birthday. She was a longtime member and Fellow (1994) of AGU and a world‐renowned atmospheric scientist. She began her research career at Woods Hole Oceanographic Institution, on Cape Cod, Massachusetts, and continued at such distinguished institutions as University of California, Los Angeles; the Experimental Meteorology Laboratory of the National Oceanic and Atmospheric Administration (NOAA), in Miami, Fla.; University of Virginia, Charlottesville; and finally as chief scientist for meteorology at NASA Goddard Laboratory for Atmospheres, Greenbelt, Md.
Mitochondrial fission and fusion
Authors: Scott Iain , Youle Richard J.
Published: June 2010

Mitochondria are highly dynamic cellular organelles, with the ability to change size, shape and position over the course of a few seconds. Many of these changes are related to the ability of mitochondria to undergo the highly co-ordinated processes of fission (division of a single organelle into two or more independent structures) or fusion (the opposing reaction). These actions occur simultaneously and continuously in many cell types, and the balance between them regulates the overall morphology of mitochondria within any given cell. Fission and fusion are active processes which require many specialized proteins, including mechanical enzymes that physically alter mitochondrial membranes, and adaptor proteins that regulate the interaction of these mechanical proteins with organelles. Although not fully understood, alterations in mitochondrial morphology appear to be involved in several activities that are crucial to the health of cells. In the present chapter we discuss the mechanisms behind mitochondrial fission and fusion, and discuss the implications of changes in organelle morphology during the life of a cell.
Mitochondria in cell death
Authors: Parsons Melissa J. , Green Douglas R.
Published: June 2010

Apoptosis can be thought of as a signalling cascade that results in the death of the cell. Properly executed apoptosis is critically important for both development and homoeostasis of most animals. Accordingly, defects in apoptosis can contribute to the development of autoimmune disorders, neurological diseases and cancer. Broadly speaking, there are two main pathways by which a cell can engage apoptosis: the extrinsic apoptotic pathway and the intrinsic apoptotic pathway. At the centre of the intrinsic apoptotic signalling pathway lies the mitochondrion, which, in addition to its role as the bioenergetic centre of the cell, is also the cell’s reservoir of pro-death factors which reside in the mitochondrial IMS (intermembrane space). During intrinsic apoptosis, pores are formed in the OMM (outer mitochondrial membrane) of the mitochondria in a process termed MOMP (mitochondrial outer membrane permeabilization). This allows for the release of IMS proteins; once released during MOMP, some IMS proteins, notably cytochrome c and Smac/DIABLO (Second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI), promote caspase activation and subsequent cleavage of structural and regulatory proteins in the cytoplasm and the nucleus, leading to the demise of the cell. MOMP is achieved through the co-ordinated actions of pro-apoptotic members and inhibited by anti-apoptotic members of the Bcl-2 family of proteins. Other aspects of mitochondrial physiology, such as mitochondrial bioenergetics and dynamics, are also involved in processes of cell death that proceed through the mitochondria. Proper regulation of these mitochondrial functions is vitally important for the life and death of the cell and for the organism as a whole.
Approaching ideal weak link behavior with three dimensional aluminum nanobridges
Authors: Vijay R. , Levenson-Falk E. M. , Slichter D. H. , Siddiqi I.
Published: June 2010

We investigate unshunted dc superconducting quantum interference devices (SQUIDs) consisting of aluminum nanobridges of varying length L contacted with (two dimensional, or 2D) and (three dimensional, or 3D) banks. 3D nanobridge SQUIDs with L≤150 nm (approximately four times the superconducting coherence length) exhibit ≈70% critical current modulation with applied magnetic field, approaching the theoretical limit for an ideal short metallic weak link. In contrast, 2D nanobridge SQUIDs exhibit significantly lower critical current modulation. This enhanced nonlinearity makes 3D nanobridge Josephson junctions well suited to optimize sensitivity in weak link SQUID magnetometers as well as realize ultralow-noise amplifiers and qubits.
Surface 210 nm light emission from an AlN p–n junction light-emitting diode enhanced by A-plane growth orientation
Authors: Taniyasu Yoshitaka , Kasu Makoto
Published: June 2010

( 11 2 ¯ 0 ) A-plane AlN p–n junction light-emitting diode (LED) with a wavelength of 210 nm is demonstrated. The electroluminescence from the A-plane LED is inherently polarized for the electric field parallel to the [0001] c-axis due to a negative crystal-field splitting energy. The polarization ratio (electric-field component ratio of parallel and perpendicular to c-axis) is as high as 0.9. The radiation pattern of the A-plane LED shows higher emission intensity along the surface normal, while that of a conventional (0001) C-plane LED shows lower emission intensity along the surface normal. The different radiation patterns can be explained by the polarization property.
Electromechanical probing of ionic currents in energy storage materials
Authors: Morozovska A. N. , Eliseev E. A. , Kalinin S. V.
Published: June 2010

The electrochemical processes in energy storage materials are generally linked with changes of molar volume of the host compound. Here, the frequency dependent strain response of one-dimensional electrochemically active system to periodic electric bias is analyzed. The sensitivity and resolution of electrochemical strain measurements are compared to the current-based electrochemical impedance spectroscopy. The resolution and detection limits of interferometric and atomic force microscopy based systems for probing electrochemical reactions on the nanoscale are analyzed.
The origin of large overestimation of the magnetic entropy changes calculated directly by Maxwell relation
Authors: Cui Weibin , Liu Wei , Zhang Zhidong
Published: June 2010

By investigating the nature of the first-order magnetostructural phase transition, we point out the origin of large overestimation of magnetic entropy changes calculated by directly applying the Maxwell relation. Furthermore, if the mass variations in ferromagnetic and paramagnetic phases on temperature are taken into consideration in two-phase region, taking MnAsCx, (Mn, Al)As, and Mn0.994Fe0.004As compounds as example, based on the modified Maxwell relation, the large overestimation and discrepancy of magnetic entropy changes disappear. The magnetic entropy changes are equivalent with the values by Clausius–Claperyon equation, indicating the validity of this modified approach.
Observations of temporal group delays in slow-light multiple coupled photonic crystal cavities
Authors: Kocaman S. , Yang X. , McMillan J. F. , Yu M. B. , Kwong D. L. , Wong C. W.
Published: June 2010

We demonstrate temporal group delays in coherently coupled high-Q multicavity photonic crystals, in an all-optical analog to electromagnetically induced transparency. We report deterministic control of the group delay up to 4× the single cavity lifetime in our room-temperature chip. Supported by three-dimensional numerical simulations and theoretical analyses, our multipump beam approach enables control of the multicavity resonances and intercavity phase, in both single and double transparency peaks. The standing-wave wavelength-scale photon localization allows direct scalability for chip-scale optical pulse trapping and coupled-cavity quantum electrodynamics.
Upper limit for the modulation bandwidth of a quantum dot laser
Authors: Asryan Levon V. , Suris Robert A.
Published: June 2010

We derive a closed-form expression for the upper limit for the modulation bandwidth of a semiconductor quantum dot (QD) laser. The highest possible bandwidth increases directly with overlap integral of the electron and hole wave functions in a QD, number of QD-layers, and surface density of QDs in a layer, and is inversely proportional to the inhomogeneous line broadening caused by the QD-size dispersion. At 10% QD-size fluctuations and 100% overlap, the upper limit for the modulation bandwidth in a single QD-layer laser can be as high as 60 GHz.
Aharonov–Bohm ring with a side-coupled quantum dot array as a spin switch
Authors: An Xing-Tao , Liu Jian-Jun
Published: June 2010

We study the spin polarization and the spin accumulation in an Aharonov–Bohm ring structure, in which a quantum dot (QD) array is side-coupled to one arm of the ring and the Rashba spin-orbit interaction exists in the other. The device can be as a spin switch by decreasing the tunneling coupling between the QD array and the ring. Moreover, we find that the spin polarization and the spin accumulation in the QD are affected by the number of the QDs in the QD array and can be controlled by the strength of the Rashba spin-orbit interaction and the bias on the Aharonov–Bohm ring.
Extremely low drift of resistance and threshold voltage in amorphous phase change nanowire devices
Authors: Mitra Mukut , Jung Yeonwoong , Gianola Daniel S. , Agarwal Ritesh
Published: June 2010

Time-dependent drift of resistance and threshold voltage in phase change memory (PCM) devices is of concern as it leads to data loss. Electrical drift in amorphous chalcogenides has been argued to be either due to electronic or stress relaxation mechanisms. Here we show that drift in amorphized Ge2Sb2Te5 nanowires with exposed surfaces is extremely low in comparison to thin-film devices. However, drift in stressed nanowires embedded under dielectric films is comparable to thin-films. Our results shows that drift in PCM is due to stress relaxation and will help in understanding and controlling drift in PCM devices.
PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer
Authors: VanHouten Joshua , Sullivan Catherine , Bazinet Caroline , Ryoo Tom , Camp Robert , Rimm David L. , Chung Gina , Wysolmerski John
Published: June 2010

After lactation, weaning causes mammary epithelial cell (MEC) apoptosis. MECs express the plasma membrane calcium-ATPase 2 (PMCA2), which transports calcium across the apical surface of the cells into milk. Here we show that PMCA2 is down-regulated early in mammary involution associated with changes in MEC shape. We demonstrate that loss of PMCA2 expression raises intracellular calcium levels and sensitizes MECs to apoptosis. In contrast, overexpression of PMCA2 in T47D breast cancer cells lowers intracellular calcium and protects them from apoptosis. Finally, we show that high PMCA2 expression in breast cancers is associated with poor outcome. We conclude that loss of PMCA2 expression at weaning triggers apoptosis by causing cellular calcium crisis. PMCA2 overexpression, on the other hand, may play a role in breast cancer progression by conferring resistance to apoptosis.
Activator-Mediator binding regulates Mediator-cofactor interactions
Authors: Ebmeier Christopher C. , Taatjes Dylan J.
Published: June 2010

The 26-subunit, 1.2 MDa human Mediator complex is essential for expression of perhaps all protein-coding genes. Activator binding triggers major structural shifts within Mediator, suggesting a straightforward means to spatially and temporally regulate Mediator activity. By using mass spectrometry (MudPIT) and other techniques, we have compared the subunit composition of Mediator in three different structural states: bound to the activator SREBP-1a, VP16, or an activator-free state. As expected, consensus Mediator subunits were similarly represented in each sample. However, we identify a set of cofactors that interact specifically with activator-bound but not activator-free Mediator, suggesting activator binding triggers new Mediator-cofactor interactions. Furthermore, MudPIT combined with biochemical assays reveals a nonoverlapping set of coregulatory factors associated with SREBP-Mediator vs. VP16-Mediator. These data define an expanded role for activators in regulating gene expression in humans and suggest that distinct, activator-induced structural shifts regulate Mediator function in gene-specific ways.
The orphan nuclear hormone receptor
ERR
β controls rod photoreceptor survival
Authors: Onishi Akishi , Peng Guang-Hua , Poth Erin M. , Lee Daniel A. , Chen Jichao , Alexis Uel , de Melo Jimmy , Chen Shiming , Blackshaw Seth
Published: June 2010

Mutation of rod photoreceptor-enriched transcription factors is a major cause of inherited blindness. We identified the orphan nuclear hormone receptor estrogen-related receptor β (
ERR
β) as selectively expressed in rod photoreceptors. Overexpression of
ERR
β induces expression of rod-specific genes in retinas of wild-type as well as
Nrl
−/−
mice, which lack rod photoreceptors. Mutation of
ERR
β results in dysfunction and degeneration of rods, whereas inverse agonists of
ERR
β trigger rapid rod degeneration, which is rescued by constitutively active mutants of
ERR
β.
ERR
β coordinates expression of multiple genes that are rate-limiting regulators of ATP generation and consumption in photoreceptors. Furthermore, enhancing
ERR
β activity rescues photoreceptor defects that result from loss of the photoreceptor-specific transcription factor Crx. Our findings demonstrate that
ERR
β is a critical regulator of rod photoreceptor function and survival, and suggest that
ERR
β agonists may be useful in the treatment of certain retinal dystrophies.
Ouabain modulates epithelial cell tight junction
Authors: Larre Isabel , Lazaro Amparo , Contreras Ruben G. , Balda Maria S. , Matter Karl , Flores-Maldonado Catalina , Ponce Arturo , Flores-Benitez David , Rincon-Heredia Ruth , Padilla-Benavides Teresita , Castillo Aída , Shoshani Liora , Cereijido Marcelino
Published: June 2010

Epithelial cells treated with high concentrations of ouabain (e.g., 1 μM) retrieve molecules involved in cell contacts from the plasma membrane and detach from one another and their substrates. On the basis of this observation, we suggested that ouabain might also modulate cell contacts at low, nontoxic levels (10 or 50 nM). To test this possibility, we analyzed its effect on a particular type of cell–cell contact: the tight junction (TJ). We demonstrate that at concentrations that neither inhibit K
+
pumping nor disturb the K
+
balance of the cell, ouabain modulates the degree of sealing of the TJ as measured by transepithelial electrical resistance (TER) and the flux of neutral 3 kDa dextran (J
DEX
). This modulation is accompanied by changes in the levels and distribution patterns of claudins 1, 2, and 4. Interestingly, changes in TER, J
DEX
, and claudins behavior are mediated through signal pathways containing ERK1/2 and c-Src, which have distinct effects on each physiological parameter and claudin type. These observations support the theory that at low concentrations, ouabain acts as a modulator of cell–cell contacts.
Vectors and parameters that enhance the efficacy of RNAi-mediated gene disruption in transgenic
Drosophila
Authors: Haley Benjamin , Foys Bryon , Levine Michael
Published: June 2010

Whole-genome transgenic RNAi libraries permit systematic genetic screens in individual tissues of
Drosophila
. However, there is a high incidence of nonspecific phenotypes because of off-target effects. To minimize such effects, it is essential to obtain a deeper understanding of the specificity of action of RNAi. Here, in vivo assays are used to determine the minimum, contiguous nucleotide pairing required between an siRNA and a target mRNA to generate a phenotype. We observe that as few as 16 nucleotides of contiguous homology are sufficient to attenuate gene activity. This finding provides an explanation for the high incidence of off-target effects observed in RNAi-based genetic screens. Toward improving the efficacy of RNAi-induced phenotypes in vivo
,
we describe siRNA expression vectors that allow coexpression of one or more siRNAs with a fluorescent reporter gene in cultured cells or transgenic flies. This expression system makes use of the small intron from the
ftz
segmentation gene to provide efficient processing of synthetic siRNAs from a reporter transcript. These studies provide a foundation for the specific and effective use of gene silencing in transgenic
Drosophila
.
Patrons and petits patrons: knowledge and hierarchy in illicit networks of trade in archaeological objects in the Baniko region of Mali
Authors: Panella Cristiana
Published: June 2010

This article focuses on the hierarchical relationships governing the local illicit trading networks in terracotta antiquities in the region of Baniko, in Mali. The level of authority and social control at the heart of the network lessens with each link in the chain, as a result of the monopoly and the fragmentation of knowledge. The article demonstrates that the social organisation of the network corresponds to a hierarchical habitus that ensures that the status quo of the dominant actors (urban antique dealers, rural antique dealers and intermediaries) is maintained through the economic dependence of the rural diggers, the monopoly of information and control of the network. Analysis of the first links in the network shows that action by rural intermediaries in the chain with respect to the weak links in the chain (the rural diggers) reproduces ‘micropolitics of power’ that are modelled on the same strategies of compartmentalisation of the local links, as used by the dominant actors on the rural intermediaries.
Learning transcriptional networks from the integration of ChIP–chip and expression data in a non-parametric model
Authors: Youn Ahrim , Reiss David J. , Stuetzle Werner
Published: June 2010

Results: We have developed LeTICE (Learning Transcriptional networks from the Integration of ChIP–chip and Expression data), an algorithm for learning a transcriptional network from ChIP–chip and expression data. The network is specified by a binary matrix of transcription factor (TF)–gene interactions partitioning genes into modules and a background of genes that are not involved in the transcriptional regulation. We define a likelihood of a network, and then search for the network optimizing the likelihood.

We applied LeTICE to the location and expression data from yeast cells grown in rich media to learn the transcriptional network specific to the yeast cell cycle. It found 12 condition-specific TFs and 15 modules each of which is highly represented with functions related to particular phases of cell-cycle regulation.

Availability: Our algorithm is available at http://linus.nci.nih.gov/Data/YounA/LeTICE.zip

Contact:  youna2@mail.nih.gov

Supplementary Information:  Supplementary data are available at Bioinformatics online.
adephylo: new tools for investigating the phylogenetic signal in biological traits
Authors: Jombart Thibaut , Balloux François , Dray Stéphane
Published: June 2010

Summary:  adephylo is a package for the R software dedicated to the analysis of comparative evolutionary data. Phylogenetic comparative methods initially aimed at accounting for or removing the effects of phylogenetic signal in the analysis of biological traits. However, recent approaches have shown that considerable information can be gathered from the study of the phylogenetic signal. In particular, close examination of phylogenetic structures can unveil interesting evolutionary patterns. For this purpose, we developed the package adephylo that provides tools for quantifying and describing the phylogenetic structures of biological traits. adephylo implements tests of phylogenetic signal, phylogenetic distances and proximities, and novel methods for describing further univariate and multivariate phylogenetic structures. These tools open up new perspectives in the analysis of evolutionary comparative data.

Availability: The stable version is available from CRAN: http:/cran.r-project.org/web/packages/adephylo/. The development version is hosted by R-Forge: http://r-forge.r-project.org/projects/adephylo/. Both versions can be installed directly from R. adephylo is distributed under the GNU General Public Licence (≥2).

Contact:  t.jombart@imperial.ac.uk; dray@biomserv.univ-lyon1.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Exploring the potential of template-based modelling
Authors: Lance Braddon K. , Deane Charlotte M. , Wood Graham R.
Published: June 2010

Motivation: Template-based modelling can approximate the unknown structure of a target protein using an homologous template structure. The core of the resulting prediction then comprises the structural regions conserved between template and target. Target prediction could be improved by rigidly repositioning such single template, structurally conserved fragment regions. The purpose of this article is to quantify the extent to which such improvements are possible and to relate this extent to properties of the target, the template and their alignment.

Results: The improvement in accuracy achievable when rigid fragments from a single template are optimally positioned was calculated using structure pairs from the HOMSTRAD database, as well as CASP7 and CASP8 target/best template pairs. Over the union of the structurally conserved regions, improvements of 0.7 Å in root mean squared deviation (RMSD) and 6% in GDT_HA were commonly observed. A generalized linear model revealed that the extent to which a template can be improved can be predicted using four variables. Templates with the greatest scope for improvement tend to have relatively more fragments, shorter fragments, higher percentage of helical secondary structure and lower sequence identity. Optimal positioning of the template fragments offers the potential for improving loop modelling. These results demonstrate that substantial improvement could be made on many templates if the conserved fragments were to be optimally positioned. They also provide a basis for identifying templates for which modification of fragment positions may yield such improvements.

Contact:  braddon.lance@mq.edu.au

Supplementary information: Supplementary data are available at Bioinformatics online.
New Perspectives on Chinese Herbal Medicine (Zhong‐Yao) Research and Development
Authors: Pan Si-Yuan , Chen Si-Bao , Dong Hong-Guang , Yu Zhi-Ling , Dong Ji-Cui , Long Zhi-Xian , Fong Wang-Fun , Han Yi-Fan , Ko Kam-Ming
Published: June 2010

Synthetic chemical drugs, while being efficacious in the clinical management of many diseases, are often associated with undesirable side effects in patients. It is now clear that the need of therapeutic intervention in many clinical conditions cannot be satisfactorily met by synthetic chemical drugs. Since the research and development of new chemical drugs remain time‐consuming, capital‐intensive and risky, much effort has been put in the search for alternative routes for drug discovery in China. This narrative review illustrates various approaches to the research and drug discovery in Chinese herbal medicine. Although this article focuses on Chinese traditional drugs, it is also conducive to the development of other traditional remedies and innovative drug discovery.
San‐Huang‐Xie‐Xin‐Tang Prevents Rat Hearts from Ischemia/Reperfusion‐Induced Apoptosis through eNOS and MAPK Pathways
Authors: Liou Shu-Fen , Ke Hung-Jen , Hsu Jong-Hau , Liang Jyh-Chong , Lin Hung-Hong , Chen Ing-Jun , Yeh Jwu-Lai
Published: June 2010

San‐Huang‐Xie‐Xin‐Tang (SHXT) is a traditional Chinese medication consisting of three herbs, namely Coptidis rhizome, Scutellariae radix and Rhei rhizome. This study aimed to examine the cardioprotective effects of SHXT in a rat model of acute myocardial apoptosis induced by ischemia/reperfusion (I/R). Vehicle (intravenous saline) or SHXT (intravenous or oral) was administered prior to I/R (occlusion of left coronary artery for 45 min followed by reperfusion for 2 h). In the vehicle group, myocardial I/R caused myocardial infarction with increased plasma cardiac enzymes, severe arrhythmia and mortality. Myocardial apoptosis was induced by I/R as evidenced by DNA ladder and Bcl‐2/Bax ratio. In the SHXT group, we found that SHXT significantly reduced plasma levels of cardiac enzymes, arrhythmia scores (from 5 ± 1 to 2 ± 1, P < .01) and mortality rate (from 53 to 0%, P < .01). In addition, pretreatment with intravenous SHXT reduced the infarct size dose‐dependently when compared with the vehicle group (10 mg kg−1: 14.0 ± 0.2 versus 44.5 ± 5.0%, and 30 mg kg−1: 6.2 ± 1.2% versus 44.5 ± 5.0%, both P < .01). Similarly, oral administration of SHXT reduced the infarct size dose‐dependently. Furthermore, SHXT markedly decreased the apoptosis induced by I/R with increased Bcl‐2/Bax ratio. Finally, we found that SHXT counteracted the I/R‐induced downstream signaling, resulting in increased myocardial eNOS expression and plasma nitrite, and decreased activation of ERK1/2, p38 and JNK. These data suggest that SHXT has cardioprotective effects against I/R‐induced apoptosis, and that these effects are mediated, at least in part, by eNOS and MAPK pathways.
Pulse Width Modulation Electro‐Acupuncture on Cardiovascular Remodeling and Plasma Nitric Oxide in Spontaneously Hypertensive Rats
Authors: Xiong Xuan , You Chao , Feng Qiu-Chao , Yin Ting , Chen Zhong-Ben , Ball Patrick , Wang Le-Xin
Published: June 2010

This study was designed to investigate the effect of pulse width modulation electro‐acupuncture (PWM‐EA) on cardiovascular remodeling and nitric oxide (NO) in spontaneously hypertensive rats (SHR). Thirty‐four male SHR were randomly divided into control, captopril, and two PWM‐EA groups, which were treated with 350 Hz (SHR‐350 Hz) and whole audio bandwith electro‐acupuncture (SHR‐WAB group) respectively, on the ST 36 point located on the outside of the hind leg. Systolic blood pressure (BP), plasma and myocardial NO were measured. Histological studies were also performed on the aortic wall and the left ventricle. The BP in the SHR‐350 Hz, SHR‐WAB and the captopril groups was lower than in the control group following the treatment (P< .05). The average aortic media wall thickness in the two electro‐acupuncture groups was less than in the control group (P< .05). The left ventricle/heart weight ratio in the captopril and SHR‐350 Hz groups was less than in the control group (P< .01), but was similar between the SHR‐WAB and the control group (P> .05). The plasma and myocardium NO levels were elevated in the captopril and the SHR‐350 Hz group (P< .05 and .01, resp.). The plasma level of NO in the SHR‐WAB group was also higher than in the control group (P< .05). We concluded that pulse width modulation electro‐acupuncture on the ST 36 point prevents the progression of hypertension and diminishes the cardiovascular remodeling in SHR. It also elevates plasma and cardiac NO in this animal model.
Cardiac output does not limit submaximal exercise capacity in patients with chronic heart failure
Authors: Shelton Rhidian J. , Ingle Lee , Rigby Alan S. , Witte Klaus K. , Cleland John G.F. , Clark Andrew L.
Published: June 2010

Aims

Mechanisms of exercise limitation in patients with chronic heart failure (CHF) are incompletely understood. During matched submaximal, fixed‐rate exercise, oxygen uptake is similar in patients and healthy controls. However, the importance of cardiac output (CO) remains unresolved. We aimed to determine the effect of submaximal exercise on CO and other haemodynamic variables in patients with CHF using a validated non‐invasive inert gas rebreathing system.

Methods and results

Seventy‐two subjects with a mean age (±SD) of 68.2 (±8.1) years, performed fixed‐rate exercise for 3 min at 15, 30, 45, and 60 W workloads on a cycle ergometer. Cardiac output/index (CI) and oxygen uptake (VO2) were determined at each stage by inert gas rebreathing. Subjects with systolic HF (n= 27) were compared with those without (n= 45). Cardiac index was lower in subjects with CHF at rest and throughout exercise. VO2was the same for both groups at rest and during exercise. There was no difference in the relative or absolute increase in CI from rest to 60 W (1.70 ± 0.69 vs. 1.99 ± 0.56 L/min/m2,P= 0.102, respectively). Arterio‐venous O2saturation difference at peak exercise was 75.4 ± 10.4 vs. 63.0 ± 12.1%,P= 0.001, for CHF and non‐CHF subjects, respectively.

Conclusion

During submaximal exercise, patients with systolic heart failure are able to increase their CO to a similar extent as those without; with equal levels of oxygen consumption, but requiring a much greater degree of tissue oxygen extraction.
Prognostic impact of familial screening in dilated cardiomyopathy
Authors: Moretti Michele , Merlo Marco , Barbati Giulia , Di Lenarda Andrea , Brun Francesca , Pinamonti Bruno , Gregori Dario , Mestroni Luisa , Sinagra Gianfranco
Published: June 2010

Aims

Familial screening of patients with dilated cardiomyopathy (DCM) allows an early diagnosis of the disease in family members. It is unclear if familial forms (FDC) have a different long‐term outcome compared with sporadic DCM. Our aim was to compare the long‐term prognosis of FDC and sporadic forms in order to assess the role of familial screening.

Methods and results

Between 1988 and 2007, 637 DCM patients were consecutively enrolled. Of these, 130 patients (20.4%) had FDC, including 82 (12.9%) probands and 48 (7.5%) non‐proband FDC patients (NP‐FDC), identified by family screening. We compared the 48 NP‐FDC patients with a sample of 96 patients with sporadic DCM, who were randomly matched by year of enrolment in a 2:1 ratio. At enrolment the NP‐FDC patients were younger (40 ± 16 vs. 48 ± 13 years, P = 0.002), less symptomatic [New York Heart Association, (NYHA) III–IV: 8 vs. 28%, P = 0.006], had higher left ventricular ejection fraction (35 ± 10 vs. 30 ± 9%, P = 0.005) and were less intensively treated with evidence‐based drugs than the sporadic DCM patients. Survival free from heart transplant at 2, 5 and 10 years was 93, 91 and 82%, respectively, in NP‐FDC patients compared with 86, 76 and 62% in sporadic forms (P = 0.04). After stratification for NYHA classes, no difference in survival was observed between sporadic and NP‐FDC patients.

Conclusion

Our study demonstrates that family screening can effectively identify DCM patients at an earlier stage of disease and can improve survival. The possibility of changing the prognosis of DCM needs to be verified in patients intensively treated with tailored medical treatment. Family screening should be recommended for all DCM patients.
Standardizing blue ling landings per unit effort from industry haul-by-haul data using generalized additive models
Authors: Lorance Pascal , Pawlowski Lionel , Trenkel Verena M.
Published: June 2010

Lorance, P., Pawlowski, L., and Trenkel, V. M. 2010. Standardizing blue ling landings per unit effort from industry haul-by-haul data using generalized additive models. – ICES Journal of Marine Science, 67: 1650–1658. Haul-by-haul data derived from skippers' personal logbooks, from the French deep-water fishery to the west of the British Isles, were used to calculate standardized blue ling (Molva dypterygia) landings per unit effort (lpue) for the period 2000–2008. Lpue values were estimated using generalized additive models with depth, vessel, statistical rectangle, area, and year as explanatory variables. Because of their statistical distribution, landings were modelled by a Tweedie distribution, which allows datasets to contain many zeros. To investigate how to track stock trends reliably, lpue values were estimated in five areas for different subsets of the data. The subsets consisted of hauls during the spawning season (when blue ling aggregate), outside the spawning season, and hauls in which blue ling was only a bycatch. The results suggest that blue ling lpue values have been stable over the period 2000–2008, and that the declining trend previously observed for the stock has been halted. This finding is consistent with stable mean lengths in the landings during the same period. The study demonstrates the greater suitability of haul-by-haul data than EC logbook data for deriving abundance indices for deep-water stocks.
Role of Confocal Endomicroscopy in the Diagnosis of Celiac Disease
Authors: Venkatesh Krishnappa , Abou‐Taleb Ashraf , Cohen Marta , Evans Clair , Thomas Steven , Oliver Philip , Taylor Christopher , Thomson Mike
Published: June 2010

Background and Aims:

Confocal laser endomicroscopy (CLE) is a recent development that enables surface and subsurface imaging of living cells in vivo at 1000× magnification. The aims of the present study were to define confocal features of celiac disease (CD) and to evaluate the usefulness of the CLE in the diagnosis of CD in children in comparison to histology.

Patients and Methods:

Nine patients (8 girls) with a median age of 8.35 years (range 2–12.66 years) and a median weight of 28.3 kg (range 11–71 kg) were suspected with CD and 10 matched controls underwent oesophagogastroduodenoscopy using the confocal laser endomicroscope (EC3870CILK; Pentax, Tokyo, Japan). Histologic sections were compared with the confocal images of the same site by 2 experienced paediatric histopathologists and endoscopists, all of whom were blinded to the diagnosis.

Results:

The median procedure time was 17 minutes (range 8–25 minutes). Confocal features of CD were defined and a score was developed. A total of 1384 confocal images were collected from 9 patients and 10 controls. Five images from each patient and control were selected and compared with the biopsy specimen of the same site. The sensitivity, specificity, and positive predictive value for the confocal images in comparison to the histology were 100%, 80%, and 81%. The kappa inter‐observer agreement between the 2 endoscopists was 0.769 (P = 0.018) and between the 2 histopathologists was 0.571 (P = 0.05).

Conclusions:

Confocal endomicroscopy offers the prospect of diagnosis of CD during ongoing endoscopy. It also enables targeting biopsies to abnormal mucosa and thereby increasing the diagnostic yield, especially when villous atrophy is patchy in the duodenum.
Laparoscopic Anterior Hemifundoplication Improves Key Symptoms Without Impact on GE in Children With and Children Without Neurodevelopmental Delays
Authors: Engelmann Carsten , Gritsa Stella , Gratz Klaus F , Ure Benno M
Published: June 2010

Aim:

We investigated the impact of laparoscopic anterior hemifundoplication on gastric emptying (GE) and specific symptoms in children with and children without neurodevelopmental delays gastroesophageal reflux. Scintigraphic and ultrasonographic GE measurements were correlated.

Patients and Methods:

Twenty‐six children (mean age 7 ± 6.1 years), of whom 14 were neurodevelopmentally delayed, were evaluated prospectively before 3 and 6 months after laparoscopic anterior hemifundoplication. All of the patients underwent clinical assessments, interviews, and 24‐hour pH monitoring. Key symptoms were evaluated using a 5‐point Likert scale. Gastric emptying was assessed by Tc‐99m‐DTPA‐scintigraphy and ultrasonography.

Results:

All of the children had significant catch‐up growth after fundoplication, which was more pronounced in the neurologically normal children (P < 0.05 vs impaired), in line with a decrease in the use of omeprazol (mean 0.93 ± 0.7 mg · kg−1 · day−1 before and 0.06 ± 0.18 mg · kg−1 · day−1 at 6 months after operation; P < 0.001). The 24‐hour pH monitoring normalized in all of the children, and the mean severity of the key symptoms such as vomiting, choking, and pain was significantly reduced (P < 0.001). Scintigraphic GE parameters, such as the elimination rate/minute, gastric half‐emptying time (t1/2), gastric residual activity (RA), and duration of the initial merging time, were not altered significantly by the operation (P > 0.05). Ultrasonographic evaluations confirmed these results [positive correlation with scintigraphy for t1/2 (P = 0.006) and RA (P = 0.01)]. The symptoms evolution and GE were uncorrelated (P > 0.01). There were no significant differences between children with and children without neurodevelopmental delays.

Conclusions:

Laparoscopic anterior hemifundoplication achieves an excellent symptomatic outcome without affecting GE in children with and children without neurodevelopmental delays.
Double‐balloon Enteroscopy: Pediatric Experience
Authors: Lin Tom K , Erdman Steven H
Published: June 2010

Objectives:

Double‐balloon enteroscopy (DBE) is a newly developed endoscopic modality for diagnosis and treatment of small bowel disorders. Most publications on DBE are from adult medical centers. Publication related to the use and application of DBE in children and adolescents is limited. We present our experience with the use of DBE in the pediatric age group.

Patients and Methods:

We reviewed patient information on all of the DBE procedures performed in 2006 through 2008 at a single tertiary pediatric referral center in Columbus, Ohio. Compiled information included patient demographics, procedure indications, diagnostic and therapeutic results, and procedure‐associated complications or adverse events.

Results:

Thirteen DBE procedures were performed on eleven 8‐ to 20‐year‐old patients. Procedure indications were based on suspicion for organic small bowel pathology after an exhaustive diagnostic evaluation including upper and lower endoscopy failed to uncover an etiology. Clinically significant lesions were identified in 46% (6/13) of the procedures performed. No serious procedure‐related complications occurred. Self‐limited postprocedure abdominal pain and discomfort from gaseous distension was observed in several patients.

Conclusions:

DBE appears to be a safe endoscopic modality for the diagnosis and treatment of children and adolescents with suspected small bowel disease. However, performance should be selectively reserved for patients with a high suspicion for small bowel pathology, in which other less invasive techniques have failed to adequately diagnose and treat a patient's disease.
Influence of Body Mass Index on Outcome of Pediatric Chronic Hepatitis C Virus Infection
Authors: Delgado‐Borrego Aymin , Healey David , Negre Betania , Christofi Marielle , Sabharwal Sabina , Ludwig David A , Chung Raymond T , Jonas Maureen M
Published: June 2010

Background and Aims:

Evidence demonstrates that obesity is associated with progression of chronic hepatitis C virus (HCV) infection and poor response to interferon therapy among HCV‐infected adults. However, this evidence has been confounded by multiple comorbidities present in adult cohorts and the use of single adult doses.

Patients and Methods:

We performed a retrospective investigation to evaluate the role of body mass index (BMI) in chronic HCV progression and response to therapy in the children. One hundred twenty‐three children and teenagers studied at Children's Hospital Boston for HCV infection between 1998 and 2007 were included. Patients' weight and height at the time of liver biopsy or before and after HCV therapy were obtained and BMI was calculated.

Results:

The presence of steatosis was statistically associated with higher mean (±SE) BMI percentiles (72nd ± 5.8 vs 58th ± 3.5) percentile; F(1,101) = 4.2,P= 0.04. Nonresponders to treatment had a higher mean (±SE) BMI percentile (70th ± 7.4) when compared with responders (50th ± 6.5) in univariate and multivariate analyses (P= 0.04,P= 0.02, respectively). Using a multivariate model, it was calculated that 1 standard deviation (1z‐score unit) increase in baseline BMIzscore is associated with a 12% decrease in the probability of sustained virologic response.

Conclusions:

Overweight adversely affects the progression of chronic HCV liver disease and is associated with diminished response to antiviral therapy using weight‐based dosing in a cohort with minimal comorbidities.
MMP‐2 and MMP‐9 and Their Tissue Inhibitor in Preterm Human Milk
Authors: Lubetzky Ronit , Mandel Dror , Mimouni Francis B , Herman Lea , Reich Reuven , Reif Shimon
Published: June 2010

Background and Aims:

Matrix metalloproteinases (MMPs) are a group of endopeptidases that play a key role in the degradation of the extracellular matrix. The natural inhibitors of MMPs are the tissue inhibitors of metalloproteinases (TIMPs). It has been shown that several MMPs may be major factors in tissue destruction and remodeling in necrotizing enterocolitis. We designed the present prospective observational study to determine whether specific MMPs activity and expression of their inhibitors are similar in the milk fed to preterm and term infants.

Methods:

We compared specific matrix metalloproteinases (MMP‐2 and MMP‐9) and 1 MMP inhibitor (TIMP‐1) activities or expression in human milk (HM) fed to 18 preterm infants and 13 full‐term infants, obtained at 72 hours and 1 and 2 weeks postpartum.

Results:

MMP‐2 and MMP‐9 activities were similar in both groups and did not vary over time. TIMP‐1 was significantly higher in preterm HM. TIMP‐1 expression increased significantly over time exclusively in the preterm group.

Conclusions:

There are differences in the expression of TIMP‐1 between colostrum and mature milk in preterm HM and differences in the expression of TIMP‐1 between preterm and term milk.