bluuebunny/crossref_metadata_2025 huggingface dataset:
FIELD EMISSION STUDIES OF NITROGEN-DOPED DIAMOND-LIKE CARBON FILMS DEPOSITED USING CH4/N2/Ne and CH4/NH3/Ne RF PLASMAS
Authors: KUO M. T. , MAY P. W. , GUNN A. , MARSHALL J. C. , ASHFOLD M. N. R. , ROSSER K. N.
Published: January 2005

Hydrogenated diamond-like Carbon (DLC) films have been deposited on Si substrates using CH 4-based radio-frequency plasmas. The films have been doped with nitrogen by addition of either N2 or NH 3 into the source gas mixture, producing films with up to 16% and 25% N content, respectively. The effect of additions of Ne to these gas mixtures has been investigated as a possible method to increase the growth rate and the N-content of the films. We find that addition of Ne increases the film growth rate until the Ne flow rate equals that of the CH 4, giving maximum growth rate increases of 70% and 200% for NH 3 and N 2 containing gas mixtures, respectively. At the same time the field emission threshold voltage decreases by a factor of ~0.5 and 2, respectively. With further increases in Ne flow rate, the film growth rates decrease in both cases, whilst the threshold voltage increases. Micro-combustion measurements show that the N content within the films is proportional to the percentage of the N-containing precursor in the gas phase, but is independent of Ne concentration.
CHARACTERISTIC OF MOLYBDENUM-CONTAINING a-C:H FILMS DEPOSITED USING ELECTRON CYCLOTRON RESONANCE CVD
Authors: YOON S. F. , HUANG Q. F. , RUSLI  , YANG H. , AHN J. , ZHANG Q. , SHI X.
Published: January 2005

Metal-containing carbon (Me-C:H) films are presently attracting wide interests due to their unique properties such as good adhesion, low resistivity and friction value. As a result, numerous techniques for depositing such films have been proposed. In this paper, a novel technique which involves the incorporation of two molybdenum (Mo) screen grids embedded in an electron cyclotron resonance chemical vapor deposition (ECR-CVD) system is presented. A set of film deposition experiments based on this screen grid sputtering technique has been carried out. The Mo-containing carbon films were charcterized using x-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS). The changes in film resistivity were evaluated as a function of changes in the gas flow ratio ( CH 4/ Ar ). XPS analysis showed that the fraction of Mo incorpated in the carbon film decreases drastically from 15.11% to 0.32% following an increase in the CH4/AR flow ratio. The film resistivity was found to increase by 11 orders of magnitude following the decrease in the metal fraction. It is found that Mo can exist in the forms of MoC, Mo 2 C , Mo, and even MoO 3 in the films, the last being mainly due to air exposure. The results showed that our ECR-based screen grid deposition technique for Me-C:H is highly effective and flexible with good control over the amount of metal incorporated.
STRUCTURAL AND MECHANICAL PROPERTIES OF AMORPHOUS SILICON-CARBON ALLOY FILMS DEPOSITED BY FILTERED CATHODIC VACUUM ARC TECHNIQUE
Authors: Shi J. R. , Shi X. , Sun Z. , LIU E. , Tay B. K. , Jin X. Z.
Published: January 2005

Amorphous silicon-carbon alloy films have been successfully deposited by filtered cathodic vacuum are technique. The structural and mechanical properties of the films were investigated by using x-ray photoelectron spectroscopy (XPS), Raman spectroscopy, surface profiler and nano-indenter. The silicon content in the films determined by XPS measurement varies from 2.4 to 48 at.%. Both XPS and Raman spectroscopy show the existence of silicon carbide clusters in the films containing intermediate concentration of silicon. The silicon atoms predominately substitute the carbon atom into the carbon clusters at low silicon concentration, and form amorphous silicon carbide clusters or amorphous silicon clusters at higher silicon concentration. The hardness of the films varies from 60 to 22 GPa while the stress reduces from 8.0 to 2.1 GPa.
GROWTH, CHARACTERIZATION, AND PROPERTIES OF CARBON NITRIDE WITH AND WITHOUT SILICON ADDITION
Authors: CHEN L. C. , WU C. T. , WU J.-J. , CHEN K. H.
Published: January 2005

Carbon nitride and silicon carbon nitride have been grown by microwave plasma chemical vapor deposition, electron-cyclotron-resonance plasma chemical vapor deposition, magnetron sputtering and ion beam sputtering. Depending on the specific process details, a wide range of microstructure and morphologies has been demonstrated. Effects of Si addition to CN network on the structure of the deposited materials were studied. While Si involvement in CVD process was crucial for crystal growth, excessive Si incorporation led to formation of amorphous phase in PVD process. Various optical constants including the band gap and refractive index of the SiCN phases are also reported.
SINGLE-SWITCH HIGH-POWER-FACTOR ELECTRONIC BALLAST FOR COMPACT FLUORESCENT LAMPS
Authors: CHENG HUNG L. , MOO CHIN S. , YEN HAU C. , LIN TSAI F. , HUANG SHIH H.
Published: January 2005

A novel single-switch high-power-factor electronic ballast is designed for compact fluorescent lamps. The circuit configuration is originated from the integration of a buck-boost power-factor-corrector (PFC) and a Class-E load resonant inverter. Design equations are derived based on fundamental approximation and computer analyses are performed to determine circuit parameters. By operating the buck-boost converter at discontinuous conduction mode (DCM), the electronic ballast can achieve nearly unity power factor. With carefully designed circuit parameters, the active power switch can be switched on at relatively low voltage, leading to a high circuit efficiency. A prototype for a 27-W compact fluorescent lamp was built and tested to verify the analytical predictions. Satisfactory performances are obtained from the experimental results.
TRANSFORMERLESS DC–DC CONVERTERS WITH A VERY HIGH DC LINE-TO-LOAD VOLTAGE RATIO
Authors: AXELROD B. , BERKOVICH Y. , IOINOVICI A.
Published: January 2005

By splitting the output capacitor of a basic boost converter, and combining the resulting capacitors with the main switch in the form of a switched-capacitor circuit, a new step-up structure is realized. Without using a transformer, a high line-to-load DC voltage ratio is obtained. An output filter is added, as usual, in boost converters for getting a free-ripple output. The circuit compares favorably with a quadratic boost converter regarding the count of devices and efficiency, even if it presents a lower DC gain. A DC analysis of the novel converter is presented. Experimental and simulation results confirm the theoretical expectations. By increasing the number of capacitors in the switched-capacitor circuit, higher gains can be obtained. Versatility, high voltage gain and good transient response are the features of the proposed converter.
ADAPTIVE TIME-DELAYED FEEDBACK FOR CHAOS CONTROL IN A PWM SINGLE PHASE INVERTER
Authors: ROBERT B. , IU H. H. C. , FEKI M.
Published: January 2005

Many power converters exhibit chaotic behaviors and bifurcations when conventional feedback corrector are badly tuned or when parameters vary. Time-Delayed Feedback Control (TDFC) can be used to stabilize them using a state feedback delayed by the period of the unstable orbit (UPO) to be stabilized. An obvious advantage of this method is the robustness because it does not require the knowledge of an accurate model but only the period of the target UPO. In this paper, TDFC is applied to a PWM current-programmed single phase inverter concurrently with a proportional corrector in order to avoid bifurcations and chaos and to stabilize the fundamental UPO over a widened range of application. Moreover an improvement of the dynamical performances is realized by defining an adaptive law for the TDFC.
ANALYSIS AND MODELING OF A NOVEL ZVZCS FB PWM CONVERTER
Authors: SONG TINGTING , HUANG NIANCI
Published: January 2005

A novel zero-voltage and zero-current-switch (ZVZCS) full-bridge PWM converter is presented. There are neither additional active switches nor lossy components in the proposed converter to achieve ZVZCS conditions. Moreover, the ZVZCS conditions are achieved by changing the traditional configuration of ZVS-full-bridge without added control: a simple auxiliary circuit is added in the secondary and the center tap of the transformer's secondary is linked to the auxiliary circuit. The secondary rectifier voltage of the converter is clamped to a relative low level, so additional clamp circuit for the secondary rectifier is not necessary.

Using a new improved approach, which concerns the energy input into the secondary rather than the voltage in secondary, a complete small-signal model for the converter is developed through simple calculation.

The operation of the proposed converter is analyzed, some important formulas are deduced. The experimental results of a 1.2-KW prototype prove that the novel converter is successful.
NEW SINGLE UNIT RECTIFIER AND dc–dc CONVERTER
Authors: RABINOVICI RAUL , TENTSER VLADIMIR
Published: January 2005

The present paper describes a new arrangement that combines in a single unit a rectifier filter and a converter. The performances are further improved by magnetically coupling the two inductors contained in the circuit. The filter and the converter unit behave as a current source. Simulation and experimental results strengthen the theoretical approach.
ELECTRONIC BALLAST FOR HID LAMPS WITH HIGH FREQUENCY SQUARE WAVEFORM TO AVOID ACOUSTIC RESONANCES
Authors: PONCE M. , LÓPEZ A. , CORREA J. , ARAU J. , ALONSO J. M.
Published: January 2005

This paper presents a driver for a HID lamp based on the application of a high frequency current square waveform through the lamp with the goal of avoiding acoustic resonances. The proposed ballast is fed from a 12-V dc input voltage and is intended to be used in systems supplied from nonconventional sources, such as back-up batteries, photovoltaic generators and automotive applications. In order to initiate the discharge in the lamp, a specially-designed igniter supplied from the 12-V dc voltage is used to apply high voltage ignition peaks to the lamp. Experimental results obtained from a laboratory prototype for a 70-W Metal Halide lamp supplied at 30 kHz are also shown to evaluate the possibilities of the proposed topology.
NONISOLATED MULTIPHASE HALF-BRIDGE-BUCK TOPOLOGY WITH INHERENT CURRENT SHARING CAPABILITY AND SOFT-SWITCHING AND COUPLED-INDUCTORS CURRENT-DOUBLER
Authors: ABU-QAHOUQ JABER A. , MAO HONG , BATARSEH ISSA
Published: January 2005

Point-of-load DC–DC converter requirements and design are increasingly becoming stricter than ever. This is due to the required tight dynamic tolerances allowed for supply voltages and high dynamic performance demand coupled with very high power density. Moreover, as the required converter output voltage becomes smaller, higher voltage step-down ratio is required, which results in smaller switching duty cycle in the nonisolated topologies. Step-down transformer with large turns ratio is used in the isolated topologies to step-down the voltage and keep larger duty cycle. Most of the nonisolated DC–DC topologies are buck-derived and unfortunately work at hard-switching which degrades the efficiency. DC–DC interleaved buck topologies were proposed but are highly sensitive to interleaved phases asymmetry and require high performance current sharing loop. In this paper, a nonisolated multiphase nonisolated half-bridge-buck topology is presented. This topology makes it possible to achieve soft-switching, works at larger switching duty cycle with lower output voltages, and does not require current sharing loop because of the inherent current sharing capability. Moreover, a coupled-inductor current doubler topology is also presented in this paper allowing higher step-down ratio and lower output current ripple. Theoretical analysis and experimental results are presented.
EFFECTS OF INTERLEAVING ON BIFURCATION BEHAVIOR IN PARALLEL-CONNECTED BUCK CONVERTERS
Authors: IU H. H. C. , TSE C. K.
Published: January 2005

This paper studies the effect of interleaving operation on the bifurcation behavior in a system of parallel-connected dc/dc buck converters. Simulations and analysis are presented for both the cases of interleaving and synchronous operations. The effects of variation of some chosen parameters on the bifurcation behavior of the system are captured. In particular, it is found that variation of the voltage feedback gains leads to period-doubling bifurcation. Interleaving operation will discourage the occurrence of this bifurcation by widening the stable region. It is also observed that variation of output capacitance, load or switching period leads to Neimark–Sacker bifurcation. Interleaving operation will make this bifurcation more likely to occur by narrowing the stable region. In order to show the effect of interleaving operation, bifurcation boundaries of stable period-1 operation in the two cases are located and compared.
REDUCTION OF CURRENT AND VOLTAGE STRESSES IN SINGLE-STAGE AC/DC POWER FACTOR CORRECTION CONVERTERS WITH REDUCED REPEATED POWER PROCESSING AND INHERENT INPUT CURRENT CONTROL
Authors: LU DYLAN DAH-CHUAN , CHENG DAVID KI-WAI , LEE YIM-SHU
Published: January 2005

In this paper, a new family of single-stage AC/DC power factor correction converters (S2PFCC), which possesses reduced voltage stress across the storage capacitor and no extra current stress on the power switch, is proposed. The converters are realized by reduced repeated power processing concept in which part of the input power is transferred to the load directly after the first power process. This results in lower storage capacitor voltage than that of previously developed S2PFCCs but maintaining high power factor. In addition, the inherent input current control allows the load current to reduce the input line current automatically when the load becomes light, preventing excessive amount of energy being stored in the storage capacitor. Although the proposed converters employed two power switches, a simple single-loop controller for the proposed S2PFCC to achieve power factor correction (PFC) and tight output regulation is also proposed. Experimental results are reported to verify the operation and concept of the new S2PFCC.
EVALUATION OF THE CLASS E AMPLIFIER WITH TWO CURRENT SOURCES USED AS A HIGH-POWER-FACTOR ELECTRONIC BALLAST FOR COMPACT FLUORESCENT LAMPS
Authors: PONCE M. , ARAU J. , ALONSO J. M.
Published: January 2005

In this paper a novel class E amplifier with two current sources used to implement high-power-factor electronic ballast for fluorescent lamps is presented and evaluated. The circuit is based on the class E amplifier with two current sources, one of them was implemented using the main input voltage and the other by means of a bulk capacitor charged from the resonant tank of the class E amplifier. This topology presents a high power factor and low current crest factor and only uses one switch with zero voltage switching. Design guidelines are presented and a 300-kHz electronic ballast for a 32-W compact fluorescent lamp was designed and tested.
CO2 CONCENTRATING MECHANISMS IN ALGAE: Mechanisms, Environmental Modulation, and Evolution
Authors: Giordano Mario , Beardall John , Raven John A.
Published: January 2005

The evolution of organisms capable of oxygenic photosynthesis paralleled a long-term reduction in atmospheric CO2 and the increase in O2. Consequently, the competition between O2 and CO2 for the active sites of RUBISCO ribulose bisphosphate carboxylase/oxygenase became more and more restrictive to the rate of photosynthesis. In coping with this situation, many algae and some higher plants acquired mechanisms that use energy to increase the CO2 concentrations (CO2 concentrating mechanisms, CCMs CO2 concentrating mechanism ) in the proximity of RUBISCO. A number of CCM variants are now found among the different groups of algae. Modulating the CCMs may be crucial in the energetic and nutritional budgets of a cell, and a multitude of environmental factors can exert regulatory effects on the expression of the CCM components. We discuss the diversity of CCMs, their evolutionary origins, and the role of the environment in CCM modulation.
K+ currents regulate the resting membrane potential, proliferation, and contractile responses in ventricular fibroblasts and myofibroblasts
Authors: Chilton L. , Ohya S. , Freed D. , George E. , Drobic V. , Shibukawa Y. , MacCannell K. A. , Imaizumi Y. , Clark R. B. , Dixon I. M. C. , Giles W. R.
Published: January 2005

Despite the important roles played by ventricular fibroblasts and myofibroblasts in the formation and maintenance of the extracellular matrix, neither the ionic basis for membrane potential nor the effect of modulating membrane potential on function has been analyzed in detail. In this study, whole cell patch-clamp experiments were done using ventricular fibroblasts and myofibroblasts. Time- and voltage-dependent outward K+ currents were recorded at depolarized potentials, and an inwardly rectifying K+ (Kir) current was recorded near the resting membrane potential (RMP) and at more hyperpolarized potentials. The apparent reversal potential of Kir currents shifted to more positive potentials as the external K+ concentration ([K+]o) was raised, and this Kir current was blocked by 100–300 μM Ba2+. RT-PCR measurements showed that mRNA for Kir2.1 was expressed. Accordingly, we conclude that Kir current is a primary determinant of RMP in both fibroblasts and myofibroblasts. Changes in [K+]o influenced fibroblast membrane potential as well as proliferation and contractile functions. Recordings made with a voltage-sensitive dye, DiBAC3(4), showed that 1.5 mM [K+]o resulted in a hyperpolarization, whereas 20 mM [K+]o produced a depolarization. Low [K+]o (1.5 mM) enhanced myofibroblast number relative to control (5.4 mM [K+]o). In contrast, 20 mM [K+]o resulted in a significant reduction in myofibroblast number. In separate assays, 20 mM [K+]o significantly enhanced contraction of collagen I gels seeded with myofibroblasts compared with control mechanical activity in 5.4 mM [K+]o. In combination, these results show that ventricular fibroblasts and myofibroblasts express a variety of K+ channel α-subunits and demonstrate that Kir current can modulate RMP and alter essential physiological functions.
Regional Brain Activity Associated with Visual Backward Masking
Authors: Green Michael F. , Glahn David , Engel Stephen A. , Nuechterlein Keith H. , Sabb Fred , Strojwas Magda , Cohen Mark S.
Published: January 2005

In visual backward masking, the visibility of a briefly presented visual target is disrupted by a mask that is presented shortly thereafter. The goal of the current study was to identify regions in the human cortex that may provide the neural basis of visual masking. We searched for areas whose activity correlated with perception as we systematically varied the strength of masking. A total of 13 subjects performed a backward masking task during functional magnetic resonance imaging. Target and mask were presented at three delay intervals (34, 68, and 102 msec) and behavioral measures confirmed that the targets were more visible at longer masking intervals. Two sets of regions of interest were identified: Distinct regions in the visual cortex (V1/V2, LO, hMT+) were segregated using scans to localize visual processing drawn from the existing literature. Additional cortical regions were selected in a data-driven approach based on their activity during the backward masking task. For each set, we determined the regions whose magnitude of activation increased at longer masking intervals. Nine of the subjects provided valid behavioral performance data on the visual masking task and imaging data from these subjects were used for subsequent analysis. The scans of visual processing areas identified four regions, including: early visual areas (V1 and V2), the motion-sensitive regions in the lateral occipital (LO) lobe (hMT+), and two components (dorsal and ventral) of the object-sensitive region, LO. Of these, the ventral and dorsal LO regions were sensitive to the strength of the mask. For the data-driven approach, six regions were identified on the basis of a difference map in which all masking intervals were contrasted with rest. These included the inferior parietal, anterior cingulate, precentral, insula, thalamic, and occipital areas. The predicted effects of more activity with weaker masking were seen in the thalamus, inferior parietal, and anterior cingulate. This study isolated three types of visual processing areas. The first included regions that subserve key stages of vision (including object and motion processing). The second type responded to the presentation of briefly presented visual stimuli, regardless of masking interval. The third type (selected from the first two) included regions sensitive to the interval between the target and mask. These latter regions (including ventral LO, inferior parietal, anterior cingulate, and thalamus) may form the neural substrate of backward masking.
Deep-Sea Fisheries of the High Seas: The Management Impasse
Authors: Kimball Lee
Published: January 2005

This article briefly reviews the current status of high seas bottom fishing and its impacts. It then traces the evolution of major intergovernmental discussions on these issues up to the 5th meeting of the UN Informal Consultative Process on Oceans and the Law of the Sea in June 2004, including the involvement of scientists and conservation organisations. Next, it highlights the four key arguments presented to date on the need for immediate action to curtail high seas bottom trawling: that it is largely unregulated and unsustainable, severely impacts deep-sea biodiversity, and is a highly destructive fishing technique. In addition, it draws attention to an important emerging argument on equity considerations. Rights and duties regarding conservation of sedentary species on the coastal state's continental margin beyond 200 nautical miles are also considered. A final section suggests possible solutions to the management impasse regarding high seas bottom trawl fisheries, covering the authority to regulate, the need for deep ocean assessment, strengthening the international community's stake in deep-sea conservation and some of the tools available.
Managing Deep-sea Fisheries: Some Threshold Questions
Authors: Balton David , Zbicz Dorothy
Published: January 2005

Increasing fishing effort and advances in fishing technology and methods are putting new pressure on deep-sea fisheries. Multilateral efforts to manage the living marine resources over the past fifty years have met with mixed results. This paper examines multilateral approaches and measures adopted in the past decade to manage these resources. It then addresses two threshold questions to be asked in considering multilateral management of deep-sea fisheries: 1) whether new approaches should take the form of binding or non-binding measures, and 2) whether such measures should apply in all marine areas or only on the high seas. It concludes with recommended elements that should be included to maximize the chances of success for managing deep-sea fisheries.
Unregulated Deep-Sea Fisheries: A Need for a Multi-Level Approach
Authors:   Molenaar
Published: January 2005

Many deep-sea fisheries share characteristics that distinguish them from other fisheries in a way which heightens sustainability and biodiversity concerns. Due to their depth of operation, many deep-sea fisheries occur in areas where the current international law of the sea gives coastal states no jurisdiction to regulate fisheries unilaterally. Whereas many international fisheries currently suffer from unregulated fishing under irresponsible flags of convenience, the concerns on deep-sea fisheries relate first of all to the absence of (international) regulation. The approach advocated in this article would be one where complementary action is taken simultaneously at the global, regional and national levels. As there may not be enough time for conceptually sound and holistic but incremental processes for regime building, the focus should first of all be on flexible short-term action.
Managing Antarctic Marine Living Resources: The CCAMLR Approach
Authors: Miller Denzil , Sabourenkov Eugene , Ramm David
Published: January 2005

This paper documents the experiences of the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) in developing, and implementing, its fisheries conservation and management measures. Examples are given to show how the provisions of Article II of the Convention on the Conservation of Antarctic Marine Living Resources (CAMLR Convention) have been applied in practice. Generally, these provisions strive for an ecosystem-based and precautionary approach to the management of harvested and non-harvested species. Emphasis is given to the development of management measures to deal with: (a) uncertainty associated with new and exploratory fisheries, (b) reduction and elimination (i.e.minimisation) of seabird bycatch in longline fisheries, (c) trade-related measures to combat illegal, unreported and unregulated (IUU) fishing on CCAMLR species, and (d) general environmental protection. CCAMLR's achievements are evaluated, potential threats to its future effectiveness are identified and some possible counteractions are offered.
Human Rights for Immigration Detainees in Strasbourg: Limited Sovereignty or a Limited Discourse?
Authors: Cornelisse Galina
Published: January 2005

The present international legal system is so determined to protect the interests of states and their territorial boundaries that any people who seek to move across those boundaries are seen as intruders. If they can enter at all, they enter at their own risk.
Co-contribution of IP₃R and Ca²⁺ Influx Pathways to Pacemaker Ca²⁺ Activity in Stomach ICC
Authors: Liu Hong-Nian , Ohya Susumu , Furuzono Shinji , Wang Jing , Imaizumi Yuji , Nakayama Shinsuke
Published: January 2005

Intracellular Ca2+ oscillations in interstitial cells of Cajal (ICCs) are thought to be the primary pacemaker activity in the gut. In the present study, the authors prepared small tissues of 100-to 300-µm diameter (cell cluster preparation) from the stomach smooth muscle (including the myenteric plexus) of mice by enzymatic and mechanical treatments. After 2 to 4 days of culture, the intracellular Ca2+ concentration ([Ca2+]i) was measured. In the presence of nifedipine, a dihydropyridine Ca2+ channel antagonist, spontaneous [Ca2+]i oscillations were observed within limited regions showing positive c-Kitimmunoreactivity, a maker for ICCs. In the majority of cell cluster preparations with multiple regions of [Ca2+]i oscillations, [Ca2+]i oscillated synchronously in the same phase. Asmall number of cell clusters (8 of 53) showed multiple regions of [Ca2+]i oscillations synchronized but with a considerable phase shift. Neither tetrodotoxin (250 nM) nor atropine (10µM) significantly affected [Ca2+]i oscillations in the presence of nifedipine. Low concentrations (40µM) of Ni2+ had little effect on the spontaneous [Ca2+]i oscillation, but SK&F96365 (40µM) and Cd2+ (120µM) terminated it. Applications of either 2-aminoethoxydiphenyl borate (10µM) or xestosponginC(10µM) completely and rather rapidly (~2 min) abolished the spontaneous [Ca2+]i oscillations. The results suggest that pacemaker [Ca2+]i oscillations in ICCs are produced by close interaction of intracellular Ca2+ release channels, especially inositol 1,4,5-trisphosphate receptor (InsP3R) and Ca2+ influx pathways, presumably corresponding to store-operated type channels. Reverse transcription polymerase chain reaction examinations revealed expression of TRPC2, 4, and 6, as well as Ins P3R1 and 2 in ICCs.
The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus
Authors: Petit Marleen MR , Meulemans Sandra MP , Alen Philippe , Ayoubi Torik AY , Jansen Erik , Van de Ven Wim JM
Published: January 2005

Background

At sites of cell adhesion, proteins exist that not only perform structural tasks but also have a signaling function. Previously, we found that the Lipoma Preferred Partner (LPP) protein is localized at sites of cell adhesion such as focal adhesions and cell-cell contacts, and shuttles to the nucleus where it has transcriptional activation capacity. LPP is a member of the zyxin family of proteins, which contains five members: ajuba, LIMD1, LPP, TRIP6 and zyxin. LPP has three LIM domains (zinc-finger protein interaction domains) at its carboxy-terminus, which are preceded by a proline-rich pre-LIM region containing a number of protein interaction domains.

Results

To catch the role of LPP at sites of cell adhesion, we made an effort to identify binding partners of LPP. We found the tumor suppressor protein Scrib, which is a component of cell-cell contacts, as interaction partner of LPP. Human Scrib, which is a functional homologue of Drosophila scribble, is a member of the leucine-rich repeat and PDZ (LAP) family of proteins that is involved in the regulation of cell adhesion, cell shape and polarity. In addition, Scrib displays tumor suppressor activity. The binding between Scrib and LPP is mediated by the PDZ domains of Scrib and the carboxy-terminus of LPP. Both proteins localize in cell-cell contacts. Whereas LPP is also localized in focal adhesions and in the nucleus, Scrib could not be detected at these locations in MDCKII and CV-1 cells. Furthermore, our investigations indicate that Scrib is dispensable for targeting LPP to focal adhesions and to cell-cell contacts, and that LPP is not necessary for localizing Scrib in cell-cell contacts. We show that all four PDZ domains of Scrib are dispensable for localizing this protein in cell-cell contacts.

Conclusions

Here, we identified an interaction between one of zyxin's family members, LPP, and the tumor suppressor protein Scrib. Both proteins localize in cell-cell contacts. This interaction links Scrib to a communication pathway between cell-cell contacts and the nucleus, and implicates LPP in Scrib-associated functions.
Structure and evolution of the mouse pregnancy-specific glycoprotein (Psg) gene locus
Authors: McLellan Andrew S , Fischer Beate , Dveksler Gabriela , Hori Tomomi , Wynne Freda , Ball Melanie , Okumura Katsuzumi , Moore Tom , Zimmermann Wolfgang
Published: January 2005

Background

The pregnancy-specific glycoprotein (Psg) genes encode proteins of unknown function, and are members of the carcinoembryonic antigen (Cea) gene family, which is a member of the immunoglobulin gene (Ig) superfamily. In rodents and primates, but not in artiodactyls (even-toed ungulates / hoofed mammals), there have been independent expansions of the Psg gene family, with all members expressed exclusively in placental trophoblast cells. For the mouse Psg genes, we sought to determine the genomic organisation of the locus, the expression profiles of the various family members, and the evolution of exon structure, to attempt to reconstruct the evolutionary history of this locus, and to determine whether expansion of the gene family has been driven by selection for increased gene dosage, or diversification of function.

Results

We collated the mouse Psg gene sequences currently in the public genome and expressed-sequence tag (EST) databases and used systematic BLAST searches to generate complete sequences for all known mouse Psg genes. We identified a novel family member, Psg31, which is similar to Psg30 but, uniquely amongst mouse Psg genes, has a duplicated N1 domain. We also identified a novel splice variant of Psg16 (bCEA). We show that Psg24 and Psg30 / Psg31 have independently undergone expansion of N-domain number. By mapping BAC, YAC and cosmid clones we described two clusters of Psg genes, which we linked and oriented using fluorescent in situ hybridisation (FISH). Comparison of our Psg locus map with the public mouse genome database indicates good agreement in overall structure and further elucidates gene order. Expression levels of Psg genes in placentas of different developmental stages revealed dramatic differences in the developmental expression profile of individual family members.

Conclusion

We have combined existing information, and provide new information concerning the evolution of mouse Psg exon organization, the mouse Psg genomic locus structure, and the expression patterns of individual Psg genes. This information will facilitate functional studies of this complex gene family.
Fully automated synthesis of (phospho)peptide arrays in microtiter plate wells provides efficient access to protein tyrosine kinase characterization
Authors: Saxinger Carl , Conrads Thomas P , Goldstein David J , Veenstra Timothy D
Published: January 2005

Background

Synthetic peptides have played a useful role in studies of protein kinase substrates and interaction domains. Synthetic peptide arrays and libraries, in particular, have accelerated the process. Several factors have hindered or limited the applicability of various techniques, such as the need for deconvolution of combinatorial libraries, the inability or impracticality of achieving full automation using two-dimensional or pin solid phases, the lack of convenient interfacing with standard analytical platforms, or the difficulty of compartmentalization of a planar surface when contact between assay components needs to be avoided. This paper describes a process for synthesis of peptides and phosphopeptides on microtiter plate wells that overcomes previous limitations and demonstrates utility in determination of the epitope of an autophosphorylation site phospho-motif antibody and utility in substrate utilization assays of the protein tyrosine kinase, p60c-src.

Results

The overall reproducibility of phospho-peptide synthesis and multiplexed EGF receptor (EGFR) autophosphorylation site (pY1173) antibody ELISA (9H2) was within 5.5 to 8.0%. Mass spectrometric analyses of the released (phospho)peptides showed homogeneous peaks of the expected molecular weights. An overlapping peptide array of the complete EGFR cytoplasmic sequence revealed a high redundancy of 9H2 reactive sites. The eight reactive phospopeptides were structurally related and interestingly, the most conserved antibody reactive peptide motif coincided with a subset of other known EGFR autophosphorylation and SH2 binding motifs and an EGFR optimal substrate motif. Finally, peptides based on known substrate specificities of c-src and related enzymes were synthesized in microtiter plate array format and were phosphorylated by c-Src with the predicted specificities. The level of phosphorylation was proportional to c-Src concentration with sensitivities below 0.1 Units of enzyme.

Conclusions

The ability of this method to interface with various robotics and instrumentation is highly flexible since the microtiter plate is an industry standard. It is highly scalable by increasing the surface area within the well or the number of wells and does not require specialized robotics. The microtiter plate array system is well suited to the study of protein kinase substrates, antigens, binding molecules, and inhibitors since these all can be quantitatively studied at a single uniform, reproducible interface.
Reversal of a full-length mutant huntingtin neuronal cell phenotype by chemical inhibitors of polyglutamine-mediated aggregation
Authors: Wang Jin , Gines Silvia , MacDonald Marcy E , Gusella James F
Published: January 2005

Background

Huntington's disease (HD) is an inherited neurodegenerative disorder triggered by an expanded polyglutamine tract in huntingtin that is thought to confer a new conformational property on this large protein. The propensity of small amino-terminal fragments with mutant, but not wild-type, glutamine tracts to self-aggregate is consistent with an altered conformation but such fragments occur relatively late in the disease process in human patients and mouse models expressing full-length mutant protein. This suggests that the altered conformational property may act within the full-length mutant huntingtin to initially trigger pathogenesis. Indeed, genotype-phenotype studies in HD have defined genetic criteria for the disease initiating mechanism, and these are all fulfilled by phenotypes associated with expression of full-length mutant huntingtin, but not amino-terminal fragment, in mouse models. As the in vitro aggregation of amino-terminal mutant huntingtin fragment offers a ready assay to identify small compounds that interfere with the conformation of the polyglutamine tract, we have identified a number of aggregation inhibitors, and tested whether these are also capable of reversing a phenotype caused by endogenous expression of mutant huntingtin in a striatal cell line from the Hdh
Q111/Q111
knock-in mouse.

Results

We screened the NINDS Custom Collection of 1,040 FDA approved drugs and bioactive compounds for their ability to prevent in vitro aggregation of Q58-htn 1–171 amino terminal fragment. Ten compounds were identified that inhibited aggregation with IC50 < 15 μM, including gossypol, gambogic acid, juglone, celastrol, sanguinarine and anthralin. Of these, both juglone and celastrol were effective in reversing the abnormal cellular localization of full-length mutant huntingtin observed in mutant Hdh
Q111/Q111
striatal cells.

Conclusions

At least some compounds identified as aggregation inhibitors also prevent a neuronal cellular phenotype caused by full-length mutant huntingtin, suggesting that in vitro fragment aggregation can act as a proxy for monitoring the disease-producing conformational property in HD. Thus, identification and testing of compounds that alter in vitro aggregation is a viable approach for defining potential therapeutic compounds that may act on the deleterious conformational property of full-length mutant huntingtin.
Systems validation: application to statistical programs
Authors: Carter Rickey E
Published: January 2005

Background

In 2003, the United States Food and Drug Administration (FDA) released a guidance document on the scope of "Part 11" enforcement. In this guidance document, the FDA indicates an expectation of a risk-based approach to determining which systems should undergo validation. Since statistical programs manage and manipulate raw data, their implementation should be critically reviewed to determine whether or not they should undergo validation. However, the concepts of validation are not often discussed in biostatistics curriculum.

Discussion

This paper summarizes a "Plan, Do, Say" approach to validation that can be incorporated into statistical training so that biostatisticians can understand and implement validation principles in their research.

Validation is a process that requires dedicated attention. The process of validation can be easily understood in the context of the scientific method.
Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study
Authors: Yip Agustín G , Green Robert C , Huyck Matthew , Cupples L Adrienne , Farrer Lindsay A ,   for the MIRAGE Study Group
Published: January 2005

Background

Nonsteroidal anti-inflammatory drugs (NSAID) use may protect against Alzheimer's disease (AD) risk. We sought examine the association between NSAID use and risk of AD, and potential effect modification by APOE-ε4 carrier status and ethnicity.

Methods

The MIRAGE Study is a multi-center family study of genetic and environmental risk factors for AD. Subjects comprised 691 AD patients (probands) and 973 family members enrolled at 15 research centers between 1996 and 2002. The primary independent and dependent variables were prior NSAID use and AD case status, respectively. We stratified the dataset in order to evaluate whether the association between NSAID use and AD was similar in APOE-ε4 carriers and non-carriers. Ethnicity was similarly examined as an effect modifier.

Results

NSAID use was less frequent in cases compared to controls in the overall sample (adjusted OR = 0.64; 95% CI = 0.38–1.05). The benefit of NSAID use appeared more pronounced among APOE-ε4 carriers (adjusted OR = 0.49; 95% CI = 0.24–0.98) compared to non-carriers, although this association was not statistically significant. The pattern of association was similar in Caucasian and African Americans.

Conclusions

NSAID use is inversely associated with AD and may be modified by APOE genotype. Prospective studies and clinical trials of sufficient power to detect effect modification by APOE-ε4 carrier status are needed.
Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment
Authors: Keiser Philip H , Sension Michael G , DeJesus Edwin , Rodriguez Allan , Olliffe Jeffrey F , Williams Vanessa C , Wakeford John H , Snidow Jerry W , Shachoy-Clark Anne D , Fleming Julie W , Pakes Gary E , Hernandez Jaime E ,   for the ESS40003 Study Team
Published: January 2005

Background

Hyperlipidemia secondary to protease inhibitors (PI) may abate by switching to anti-HIV medications without lipid effects.

Method

An open-label, randomized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia (fasting serum total cholesterol >200 mg/dL) who were randomized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily (n = 52) or a regimen in which their PI was continued (n = 52) for 28 weeks. All patients had undetectable viral loads (HIV-1 RNA <50 copies/mL) at baseline and were naïve to abacavir and non-nucleoside reverse transcriptase inhibitors.

Results

At baseline, the mean total cholesterol was 243 mg/dL, low density lipoprotein (LDL)-cholesterol 149 mg/dL, high density lipoprotein (HDL)-cholesterol 41 mg/dL, and triglycerides 310 mg/dL. Mean CD4+ cell counts were 551 and 531 cells/mm3 in the abacavir-switch and PI-continuation arms, respectively. At week 28, the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol (-42 vs -10 mg/dL, P < 0.001), LDL-cholesterol (-14 vs +5 mg/dL, P = 0.016), and triglycerides (-134 vs -36 mg/dL, P = 0.019) than the PI-continuation arm, with no differences in HDL-cholesterol (+0.2 vs +1.3 mg/dL, P = 0.583). A higher proportion of patients in the abacavir-switch arm had decreases in protocol-defined total cholesterol and triglyceride toxicity grades, whereas a smaller proportion had increases in these toxicity grades. At week 28, an intent-to treat: missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA <400 or <50 copies/mL or adjusted mean change from baseline in CD4+ cell count. Two possible abacavir-related hypersensitivity reactions were reported. No significant changes in glucose, insulin, insulin resistance, C-peptide, or waist-to-hip ratios were observed in either treatment arm, nor were differences in these parameters noted between treatments.

Conclusion

In hyperlipidemic, antiretroviral-experienced patients with HIV-1 RNA levels <50 copies/mL and CD4+ cell counts >500 cells/mm3, substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period, and it simplifies treatment.
Obsessive-compulsive disorder and trichotillomania: a phenomenological comparison
Authors: Lochner Christine , Seedat Soraya , du Toit Pieter L , Nel Daniel G , Niehaus Dana JH , Sandler Robin , Stein Dan J
Published: January 2005

Background

Similarities between obsessive-compulsive disorder (OCD) and trichotillomania (TTM) have been widely recognized. Nevertheless, there is evidence of important differences between these two disorders. Some authors have conceptualized the disorders as lying on an OCD spectrum of conditions.

Methods

Two hundred and seventy eight OCD patients (n = 278: 148 male; 130 female) and 54 TTM patients (n = 54; 5 male; 49 female) of all ages were interviewed. Female patients were compared on select demographic and clinical variables, including comorbid axis I and II disorders, and temperament/character profiles.

Results

OCD patients reported significantly more lifetime disability, but fewer TTM patients reported response to treatment. OCD patients reported higher comorbidity, more harm avoidance and less novelty seeking, more maladaptive beliefs, and more sexual abuse. OCD and TTM symptoms were equally likely to worsen during menstruation, but OCD onset or worsening was more likely associated with pregnancy/puerperium.

Conclusions

These findings support previous work demonstrating significant differences between OCD and TTM. The classification of TTM as an impulse control disorder is also problematic, and TTM may have more in common with conditions characterized by stereotypical self-injurious symptoms, such as skin-picking. Differences between OCD and TTM may reflect differences in underlying psychobiology, and may necessitate contrasting treatment approaches.
Tetanus immunity in nursing home residents of Bolu, Turkey
Authors: Karabay Oguz , Ozkardes Fatma , Tamer Ali , Karaarslan Kazım
Published: January 2005

Background

Tetanus is a serious but vaccine-preventable disease and fatality rate of the disease is high in the neonates and the elderly. The aim of this study was to detect the tetanus antibody prevalence in the over sixty-year age residents of the nursing homes in Bolu.

Methods

A voluntary-based study was done in the residents of two nursing homes in Bolu, Turkey. Blood samples were taken from 71 volunteers residing in there nursing homes. Tetanus IgG antibodies were measured by a commercial ELISA kit.

Results

Among overall subjects, only 11 (15.7 %) had the protective tetanus antibody titers at the time of the study. Totally, 10 subjects were examined in emergency rooms due to trauma or accidents within the last ten years and, four (40%) of them had protective antibody levels. Of the remaining 61 subjects only 7 (11%) had protective antibody levels (p < 0.05) [Relative Risk = 3.49, 95% Confidence Interval 1.24–9.77].

Conclusions

Tetanus antibody level is below the protective level in the majority of the over-sixty-year-age subjects residing in the nursing homes. Each over sixty-year age person in our country should be vaccinated. Until this is accomplished, at least, nursing home residents should be vaccinated during registration.
Clinical and cost effectiveness of mechanical support for severe ankle sprains: design of a randomised controlled trial in the emergency department [ISRCTN 37807450]
Authors: Lamb SE , Nakash RA , Withers EJ , Clark M , Marsh JL , Wilson S , Hutton JL , Szczepura A , Dale JR , Cooke MW ,   the Collaborative Ankle Support Trial research team (CAST)
Published: January 2005

Background

The optimal management for severe sprains (Grades II and III) of the lateral ligament complex of the ankle is unclear. The aims of this randomised controlled trial are to estimate (1) the clinical effectiveness of three methods of providing mechanical support to the ankle (below knee cast, Aircast® brace and Bledsoe® boot) in comparison to Tubigrip®, and (2) to compare the cost of each strategy, including subsequent health care costs.

Methods/design

Six hundred and fifty people with a diagnosis of severe sprain are being identified through emergency departments. The study has been designed to complement routine practice in the emergency setting. Outcomes are recovery of mobility (primary outcome) and usual activity, residual symptoms and need for further medical, rehabilitation or surgical treatment. Parallel economic and qualitative studies are being conducted to aid interpretation of the results and to evaluate the cost-effectiveness of the interventions.

Discussion

This paper highlights the design, methods and operational aspects of a clinical trial of acute injury management in the emergency department.