bluuebunny/crossref_metadata_2025 huggingface dataset:
Radial profile measurement of impurity line emissions using space-resolved 3m vacuum ultraviolet spectrometer in LHD
Authors: Katai Ryuji , Morita Shigeru , Goto Motoshi
Published: September 2006

A space-resolved 3m vacuum ultraviolet (vuv) spectrometer has been developed to measure a radial (vertical) profile of impurity line emissions in the Large Helical Device (LHD). The system consists of a 3m normal incidence spectrometer equipped with a space-resolved slit and a back-illuminated charge-coupled device (CCD) detector, view-angle adjustable mirrors, and a toroidal slit. A full vertical profile of the vuv line radiated from the LHD plasma is observed with a convex cylindrical mirror by extending the view angle. The vertical profiles of intrinsic impurities of carbon (C III–C V) and externally injected impurities of neon (Ne VIII), aluminum (Al XI), and argon (Ar VIII) are successfully obtained with a time interval of 125ms in the VUV range of 500–3100Å. The ion temperature profiles are also measured from the C IV line emitted in the ergodic layer of LHD.
High efficiency extreme ultraviolet overview spectrometer: Construction and laboratory testing
Authors: Biel W. , Greiche A. , Burhenn R. , Jourdain E. , Lepere D.
Published: September 2006

The new high efficiency extreme ultraviolet overview spectrometer system (HEXOS) has been developed to study impurity concentrations and impurity transport properties in the plasma of the stellarator W7-X. The HEXOS system consists of four different grating based spectrometers, which provide large etendue and good spectral resolution over a broad wavelength range (2.5–160nm, divided into four subsections with some overlapping). The mechanical arrangement as two double spectrometers allows for a compact installation geometry on W7-X. Laboratory testing and wavelength and intensity calibrations have been performed using a dc hollow cathode discharge (24–150nm) and a pinch discharge (2.5–30nm).
Design and initial operation of lost fast-ion probe based on thin Faraday films in CHS
Authors: Isobe M. , Goto K. , Toi K. , Nagaoka K. , Suzuki C. , Yoshimura Y. , Akiyama T. , Nishimura S. , Shimizu A. , Nishiura M. , Matsuoka K. , Okamura S. , Darrow D. S. , Team CHS
Published: September 2006

The purpose of this work is to measure lost fast ions as an ion current so as to make quantitative argument on flux of fast-ion loss possible. We have designed and constructed a lost fast-ion probe based on combination of thin Faraday films and small rectangular apertures, called FLIP, for the Compact Helical System. The current generated by escaping fast ions has been successfully measured with the FLIP in neutral-beam-heated plasmas. The FLIP detected increased flux of escaping fast ions while fast-ion-driven magnetohydrodynamics instabilities appear.
Design consideration for high-energy-resolution neutron spectrometer based on associated particle detection using proton recoil telescope and time-of-flight technique for ITER
Authors: Naoi N. , Asai K. , Iguchi T. , Watanabe K. , Kawarabayashi J. , Nishitani T.
Published: September 2006

For ion temperature measurement in the ITER high power operation phase, we propose a promising high-energy-resolution neutron spectrometer based on the associated particle detection using a proton recoil telescope and a time-of-flight spectrometer. To verify the operational principle and the basic performance of this system, we have set up a prototype system through Monte Carlo simulations and carried out a preliminary experiment with a deuterium-tritium (DT) neutron beam at the Fusion Neutronics Source, JAEA. The results have demonstrated that the energy resolution could be achieved around 3.3% (in full width at half maximum) for DT neutrons. In addition, the design consideration of this system for an application to ITER is given on the detection efficiency, the applicable range in the ITER operation, and the detector lifetime.
Magnetic probe response function calibrations for plasma equilibrium reconstructions of CDX-U
Authors: Spaleta J. , Zakharov L. , Kaita R. , Majeski R. , Gray T.
Published: September 2006

A novel response function calibration technique has been developed to account for time-dependent nonaxisymmetric eddy currents near magnetic sensors in toroidal magnetic confinement devices. The response function technique provides a means to cross calibrate against all available external field coil systems to calculate the absolute sensitivity of each magnetic field sensor, even when induced eddy currents are present in the vacuum vessel wall. The response function information derived in the calibration process can be used in equilibrium reconstructions to separate plasma signals from signals due to externally produced eddy currents at magnetic field sensor locations, without invoking localized wall current distribution details. The response function technique was used for the first ever equilibrium reconstructions of spherical torus plasmas, when applied to the Current Drive Experiment-Upgrade (CDX-U) device. In conjunction with the equilibrium and stability code (ESC), equilibria were obtained for recent CDX-U experiments with lithium plasma-facing components. A description of the CDX-U magnetic sensor configuration and the response function calibration technique will be presented along with examples of resulting plasma equilibrium for CDX-U lithium wall operations.
Planar nitrogen-doped aluminum clusters AlxN− (x=3–5)
Authors: Averkiev Boris B. , Boldyrev Alexander I. , Li Xi , Wang Lai-Sheng
Published: September 2006

The electronic and geometrical structures of three nitrogen-doped aluminum clusters, AlxN− (x=3–5), are investigated using photoelectron spectroscopy and ab initio calculations. Well-resolved photoelectron spectra have been obtained for the nitrogen-doped aluminum clusters at four photon energies (532, 355, 266, and 193nm). Global minimum structure searches for AlxN− (x=3–5) and their corresponding neutrals are performed using several theoretical methods. Vertical electron detachment energies are calculated using three different methods for the lowest energy structures and low-lying isomers are compared with the experimental observations. Planar structures have been established for all the three AlxN− (x=3–5) anions from the joint experimental and theoretical studies. For Al5N−, a low-lying nonplanar isomer is also found to contribute to the experimental spectra, signifying the onset of two-dimensional to three-dimensional transition in nitrogen-doped aluminum clusters. The chemical bonding in all the planar clusters has been elucidated on the basis of molecular orbital and natural bond analyses.
Electric dipole polarizabilities and C6 dipole-dipole dispersion coefficients for sodium clusters and C60
Authors: Jiemchooroj Auayporn , Norman Patrick , Sernelius Bo E.
Published: September 2006

The frequency-dependent polarizabilities of closed-shell sodium clusters containing up to 20 atoms have been calculated using the linear complex polarization propagator approach in conjunction with Hartree-Fock and Kohn-Sham density functional theories. In combination with polarizabilities for C60 from a previous work [J. Chem. Phys. 123, 124312 (2005)], the C6 dipole-dipole dispersion coefficients for the metal-cluster-to-cluster and cluster-to-buckminster-fullerene interactions are obtained via the Casimir-Polder relation [Phys. Rev. 73, 360 (1948)]. The B3PW91 results for the polarizability of the sodium dimer and tetramer are benchmarked against coupled cluster calculations. The error bars of the reported theoretical results for the C6 coefficients are estimated to be 5%, and the results are well within the error bars of the experiment.
On the nonlinear variation of dc conductivity with dielectric relaxation time
Authors: Johari G. P. , Andersson Ove
Published: September 2006

The long-known observations that dc conductivity σdc of an ultraviscous liquid varies nonlinearly with the dielectric relaxation time τ, and the slope of the logσdc against logτ plot deviates from −1 are currently seen as two of the violations of the Debye-Stokes-Einstein equation. Here we provide a formalism using a zeroth order Bjerrum description for ion association to show that in addition to its variation with temperature T and pressure P, impurity ion population varies with a liquid’s equilibrium dielectric permittivity. Inclusion of this electrostatic effect modifies the Debye-Stokes-Einstein equation to log(σdcτ)=constant+logα, where α is the T and P-dependent degree of ionic dissociation of an electrolytic impurity. Variation of a liquid’s shear modulus with T and P would add to the nonlinearity of σdc-τ relation, as would a nonequivalence of the shear and dielectric relaxation times, proton transfer along the hydrogen bonds, or occurrence of another chemical process. This is illustrated by using the data for ultraviscous acetaminophen-aspirin liquid.
A radially resolved kinetic model for nonlocal electron ripple diffusion losses in tokamaks
Authors: Robertson Scott
Published: September 2006

A relatively simple radially resolved kinetic model is applied to the ripple diffusion problem for electrons in tokamaks. The distribution function f(r,v) is defined on a two-dimensional grid, where r is the radial coordinate and v is the velocity coordinate. Particle transport in the radial direction is from ripple and banana diffusion and transport in the velocity direction is described by the Fokker-Planck equation. Particles and energy are replaced by source functions that are adjusted to maintain a constant central density and temperature. The relaxed profiles of f(r,v) show that the electron distribution function at the wall contains suprathermal electrons that have diffused from the interior that enhance ripple transport. The transport at the periphery is therefore nonlocal. The energy replacement times from the computational model are near to the experimental replacement times for tokamak discharges in the compilation by Pfeiffer and Waltz [Nucl. Fusion 19, 51 (1979)].
Extraordinary transmission in a narrow energy band for metallic gratings with converging-diverging channels
Authors: Battula A. , Chen S. C.
Published: September 2006

Transmission metallic gratings with narrow and deep slits having the shape of converging-diverging channel (CDC) can exhibit enhanced transmission resonances for wavelengths larger than the periodicity of the grating. Using finite element method, the authors show that, by varying the gap size at the throat of CDC, the spectral locations of the transmission resonance bands can be shifted close to each other and have high transmittance in a very narrow energy band. Also, the proposed shape can lead to almost perfect transmittance for any desired wavelength by carefully optimizing the metallic material, gap at the throat of CDC, and grating parameters.
GABAAreceptor α4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol
Authors: Chandra D. , Jia F. , Liang J. , Peng Z. , Suryanarayanan A. , Werner D. F. , Spigelman I. , Houser C. R. , Olsen R. W. , Harrison N. L. , Homanics G. E.
Published: September 2006

The neurotransmitter GABA mediates the majority of rapid inhibition in the CNS. Inhibition can occur via the conventional mechanism, the transient activation of subsynaptic GABAAreceptors (GABAA-Rs), or via continuous activation of high-affinity receptors by low concentrations of ambient GABA, leading to “tonic” inhibition that can control levels of excitability and network activity. The GABAA-R α4 subunit is expressed at high levels in the dentate gyrus and thalamus and is suspected to contribute to extrasynaptic GABAA-R-mediated tonic inhibition. Mice were engineered to lack the α4 subunit by targeted disruption of theGabra4gene. α4 Subunit knockout mice are viable, breed normally, and are superficially indistinguishable from WT mice. In electrophysiological recordings, these mice show a lack of tonic inhibition in dentate granule cells and thalamic relay neurons. Behaviorally, knockout mice are insensitive to the ataxic, sedative, and analgesic effects of the novel hypnotic drug, gaboxadol. These data demonstrate that tonic inhibition in dentate granule cells and thalamic relay neurons is mediated by extrasynaptic GABAA-Rs containing the α4 subunit and that gaboxadol achieves its effects via the activation of this GABAA-R subtype.
Activation, internalization, and recycling of the serotonin 2A receptor by dopamine
Authors: Bhattacharyya Samarjit , Raote Ishier , Bhattacharya Aditi , Miledi Ricardo , Panicker Mitradas M.
Published: September 2006

Serotonergic and dopaminergic systems, and their functional interactions, have been implicated in the pathophysiology of various CNS disorders. Here, we use recombinant serotonin (5-HT) 2A (5-HT2A) receptors to further investigate direct interactions between dopamine and 5-HT receptors. Previous studies inXenopusoocytes showed that dopamine, although not the cognate ligand for the 5-HT2Areceptor, acts as a partial-efficacy agonist. At micromolar concentrations, dopamine also acts as a partial-efficacy agonist on 5-HT2Areceptors in HEK293 cells. Like 5-HT, dopamine also induces receptor-internalization in these cells, although at significantly higher concentrations than 5-HT. Interestingly, if the receptors are first sensitized or “primed” by subthreshold concentrations of 5-HT, then dopamine-induced internalization occurs at concentrations ≈10-fold lower than when dopamine is used alone. Furthermore, unlike 5-HT-mediated internalization, dopamine-mediated receptor internalization, alone, or after sensitization by 5-HT, does not depend on PKC. Dopamine-internalized receptors recycle to the surface at rates similar to those of 5-HT-internalized receptors. Our results suggest a previously uncharacterized role for dopamine in the direct activation and internalization of 5-HT2Areceptors that may have clinical relevance to the function of serotonergic systems in anxiety, depression, and schizophrenia and also to the treatment of these disorders.
Cadmium and children: Exposure and health effects
Authors: SCHOETERS GREET , HOND ELLY DEN , ZUURBIER MONIEK , NAGINIENE RIMA , VAN DEN HAZEL PETER , STILIANAKIS NIKOLAOS , RONCHETTI ROBERTO , KOPPE JANNA G.
Published: September 2006

Cadmium exposure and accumulation in the body start at young age. Exposure routes in children are mainly via food, environmental tobacco smoke and house dust. Excretion from the body is limited. Cadmium accumulation in the kidney is responsible for effects such as nephrotoxicity and osteoporosis which are observed at adult age. Cadmium exposure through inhalation is also associated with lung cancer in adulthood. Although transfer to the neonate through the placenta and through breast milk is limited, teratogenic and developmental effects were observed in experimental animals. The database on human studies involving children is limited, yet effects on motoric and perceptual behaviour in children have been associated with elevated in utero cadmium exposure. In school age children urinary cadmium levels were associated with immune suppressive effects. More studies are needed to confirm these results. Experimental data in vitro and in animals refer to effects of cadmium on the hypothalamus‐pituitary axis at different levels. This may lead to disorders of the endocrine and/or immune system. Cadmium exposure at early age should be limited as much as possible to prevent direct effects on children and to prevent accumulation of cadmium which may have serious health effects only becoming manifest at older age.
Adverse health effects of children's exposure to pesticides: What do we really know and what can be done about it
Authors: JUREWICZ JOANNA , HANKE WOJCIECH , JOHANSSON CAROLINA , LUNDQVIST CHRISTOFER , CECCATELLI SANDRA , VAN DEN HAZEL PETER , SAUNDERS MARGARET , ZETTERSTRÖM ROLF
Published: September 2006

Children may be exposed to pesticides in several ways, such as by transplacental transfer during foetal life, by intake of contaminated breast milk and other nutrients, or by contact with contaminated subjects and areas in the environment such as pets treated with insecticides, house dust, carpets and chemically treated lawns and gardens. Exposure early in life, and particularly during periods of rapid development, such as during foetal life and infancy, may have severe effects on child health and development by elevating the risk of congenital malformations, cancer, malabsorption, immunological dysfunction, endocrine disease, and neurobehavioural deficiencies. As pesticides can also interfere with parental reproductive health, exposure of parents may have consequences for the offspring leading to reduced chance of male birth and increased risk of childhood cancer.

Conclusions: Current knowledge about tolerable levels and consequences of toxic exposure to pesticides during human development is rather scarce. Owing to the high risk of exposure to pesticides, particularly in less developed countries, further elucidation by well‐controlled epidemiological studies in this field it is urgently needed. The Policy Interpretation Network on Children's Health and Environment (PINCHE), which is financed by the EU DG research has suggested actions against pesticide exposure. They have been presented and discussed in this paper. Several suggestions of PINCHE concerning action needed regarding pesticides were presented in the paper.
Environmental tobacco smoke exposure and children's health
Authors: POLANSKA KINGA , HANKE WOJCIECH , RONCHETTI ROBERTO , VAN DEN HAZEL PETER , ZUURBIER MONIEK , KOPPE JANNA G. , BARTONOVA ALENA
Published: September 2006

Almost half of the child population is involuntarily exposed to environmental tobacco smoke (ETS). The ETS exposure gives rise to an excessive risk of several diseases in infancy and childhood, including sudden infant death syndrome, upper and lower respiratory infections, asthma and middle ear diseases. It is also linked to cancer, and behavioural problems and neurocognitive deficits in children.

Conclusions: Protecting children from ETS exposure is a complex and important issue. The best improvement in children's health is to be gained when parents stop smoking or, when that is not possible, they stop smoking in their children's environment. Paediatricians, because of their authority, and their frequent and regular contact with parents, play a leading role in protecting children from ETS exposure. An ideal approach to help parents to stop smoking seems to be initial minimal‐contact advice provided by their paediatrician with feedback and supplemental printed materials, leading to greater intensity and duration of follow‐up home visits.
Air pollution: A threat to the health of our children
Authors: MOSHAMMER HANNS , BARTONOVA ALENA , HANKE WOJTEK , VAN DEN HAZEL PETER , KOPPE JANNA G. , KRÄMER URSULA , RONCHETTI ROBERTO , SRAM RADIM J. , WALLIS MAX , WALLNER PETER , ZUURBIER MONIEK
Published: September 2006

Background/methods: Current air pollution levels pose a threat to the health of children starting from conception. The scientific evidence is presented for mortality, morbidity, and sub‐clinical effects. The first section deals with exposure data, the following sections with the evidence of health effects from epidemiology and toxicology leading to recommendations.

Results: Improved air quality reduces the number of infants' deaths as well as disease and pain.

Conclusions: Medical doctors have a responsibility to know the facts and to advise their patients. Doctors when visiting their patients' homes should be aware of the possibly grave impact of the indoor environment for the respiratory health of their patients. They should recognize and advise the parents on problems associated with environmental tobacco smoke, poor ventilation, mould growth, and maintenance of heating installations. With regard to outdoor air pollution, doctors could serve as role models and also advise their patients and parents on environmentally friendly behaviour. Such behaviour not only calls for personal commitment but also for the right infrastructure to be provided (e.g. public transport, district heating). Doctors should be proactive in the community and in their country as advocates for a healthier environment for our children.
Regulation of retrotranslocation by p97-associated deubiquitinating enzyme ataxin-3
Authors: Wang Qiuyan , Li Lianyun , Ye Yihong
Published: September 2006

Misfolded proteins of the endoplasmic reticulum undergo retrotranslocation to enter the cytosol where they are degraded by the proteasome. Retrotranslocation of many substrates requires an ATPase complex consisting of the p97 ATPase and a dimeric cofactor, Ufd1-Npl4. We report that efficient elimination of misfolded ER proteins also involves ataxin-3 (atx3), a p97-associated deubiquitinating enzyme mutated in type-3 spinocerebellar ataxia. Overexpression of an atx3 mutant defective in deubiquitination inhibits the degradation of misfolded ER proteins and triggers ER stress. Misfolded polypeptides stabilized by mutant atx3 are accumulated in part as polyubiquitinated form, suggesting an involvement of its deubiquitinating activity in ER-associated protein degradation regulation. We demonstrate that atx3 transiently associates with the ER membrane via p97 and the recently identified Derlin–VIMP complex, and its release from the membrane appears to be governed by both the p97 ATPase cycle and its own deubiquitinating activity. We present evidence that atx3 may promote p97-associated deubiquitination to facilitate the transfer of polypeptides from p97 to the proteasome.
Active Screening in High-Risk Units Is an Effective and Cost-Avoidant Method to Reduce the Rate of Methicillin-ResistantStaphylococcus aureusInfection in the Hospital
Authors: Clancy Megan , Graepler Amy , Wilson Michael , Douglas Ivor , Johnson Jeff , Price Connie Savor
Published: September 2006

Objective.

To evaluate the impact of active screening for methicillin-resistantStaphylococcus aureus(MRSA) on MRSA infection rates and cost avoidance in units where the risk of MRSA transmission is high.

Methods.

During a 15-month period, all patients admitted to our adult medical and surgical intensive care units (ICUs) were screened for MRSA nasal carriage on admission and weekly thereafter. The overall rates of all MRSA infections and of nosocomial MRSA infection in the 2 adult ICUs and the general wards were compared with rates during the 15-month period prior to the start of routine screening. The percentage of patients colonized or infected with MRSA on admission and the cost avoidance of the surveillance program were also assessed.

Results.

The overall rate of MRSA infections for all 3 areas combined decreased from 6.1 infections per 1,000 census-days in the preintervention period to 4.1 infections per 1,000 census-days in the postintervention period (P= .01). The decrease remained statistically significant when only nosocomial MRSA infections were examined (4.5 vs 2.8 infections per 1,000 census-days;P<.01), despite a corresponding increase during the postintervention period in the percentage of patients with onset of MRSA infection in the first 72 hours after admission to the general wards (46% to 81%;P<.005). A total of 3.7% of ICU patients were colonized or infected with MRSA on admission; MRSA would not have been detected in 91% of these patients if screening had not been performed. At a cost of $3,475/month for the program, we averted a mean of 2.5 MRSA infections/month for the ICUs combined, avoiding $19,714/month in excess cost in the ICUs.

Conclusions.

Even in a setting of increasing community-associated MRSA, active MRSA screening as part of a multi-factorial intervention targeted to high-risk units may be an effective and cost-avoidant strategy for achieving a sustained decrease of MRSA infections throughout the hospital.
Association Between Hand Hygiene Compliance and Methicillin-Resistant Staphylococcus aureus Prevalence in a French Rehabilitation Hospital
Authors: Girou Emmanuelle , Legrand Patrick , Soing-Altrach Sophan , Lemire Astrid , Poulain Céline , Allaire Alexandra , Tkoub-Scheirlinck Latifa , Chai Steeve Ho Tam , Dupeyron Catherine , Loche Catherine-Marie
Published: September 2006

We simultaneously investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and compliance with hand hygiene in the clinical wards of a French rehabilitation hospital. We found that the rate of hand hygiene compliance observed at the patient's bedside was a strong predictor of MRSA prevalence.
Epidemiology of Community-Acquired Methicillin-Resistant Staphylococcus aures Skin Infections Among Healthcare Workers in an Outpatient Clinic
Authors: Johnston Cecilia P. , Cooper Lisa , Ruby William , Carroll Karen C. , Cosgrove Sara E. , Perl Trish M.
Published: September 2006

We describe an investigation of soft-tissue infections caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strains in 2 healthcare workers employed in an outpatient clinic for patients with human immunodeficiency virus infection. Cultures of environmental samples from multiple surfaces in the clinic grew toxin-producing CA-MRSA strains, suggesting fomites may play a role in the transmission of these strains of MRSA.
Cardiovascular Effects of and Interaction Between Calcium Blocking Drugs and Anesthetics in Chronically Instrumented Dogs. V. Role of Pharmacokinetics and the Autonomic Nervous System in the Interactions Between Verapamil and Inhalational Anesthetics
Authors: Chelly Jacques E. , Hysing Einar S. , Hill Douglas C. , Abernethy Darrell R. , Dlewati Abdallah , Doursout Marie-Francoise , Merin Robert G.
Published: September 2006

To assess the role of both pharmacokinetics and the autonomic nervous system in the interaction between inhalational anesthetics and verapamil, dogs were chronically instrumented to measure heart rate, PR interval, dP/dt, cardiac output, and aortic blood pressure. In a first group of seven dogs, studied awake and during halothane (1.2%), enflurane (2.5%), and isoflurane anesthesia (1.6%), verapamil was infused for 30 min in doses calculated to obtain similar plasma concentrations (83 ± 10, 82 ± 6, 81 ± 10, and 77 ± 9 ng • ml−1, respectively). For the latter purpose, the infusion dose was 3 and 2 µg • kg−1 •min−1 awake and during anesthesia, respectively, preceded by a loading dose of 200, 150, and 100 µg • kg−1, awake, during isoflurane, and halothane and enflurane, respectively. In awake dogs, verapamil induced an increase in heart rate (24 ± 5 bpm) and PR interval (35 ± 9 msec) and a decrease in mean arterial pressure (−5 ± 2 mmHg) and dP/dt (−494 ± 116 mmHg/s). Although plasma concentrations were similar in awake and in anesthetized dogs, the only statistically significant changes induced by verapamil were an increase in heart rate and a decrease in dP/dt during halothane and enflurane, while left atrial pressure increased only with enflurane. In a second group of six dogs, verapamil pharmacokinetics were determined in the presence and absence of a ganglionic blocking drug (chlorisondamine, 2 mg • kg−1 iv). Blockade of ganglionic transmission resulted in a decrease in both initial volume of distribution and total clearance of verapamil—changes similar to those previously reported with inhalational anesthetics.4 The authors' data demonstrate the importance of pharmacokinetics in the interaction between verapamil and inhalational anesthetics. Also demonstrated is the importance of autonomic nervous transmission blockade on the inhalational anesthetic-induced effects of verapamil properties.
Morphine and Fentanyl Hypnotic Interactions with Thiopental
Authors: Kissin Igor , Mason John O. , Bradley Edwin L.
Published: September 2006

The effects of morphine thiopental and fentanyl-thiopental combinations on the righting reflex were studied in rats. Doses that block the righting reflex for the agents given alone and for their combinations were determined with a probit procedure and compared with an isobolographic analysis. Interaction between morphine or fentanyl and thiopental on blockade of the righting reflex were both found to be synergistic. The degree of synergism was relatively small for the fentanyl-thiopental combination; the maximal deviation from additive interaction (expected/observed ratio) for ED50 dose level was 1.15 (P < 0.01). The degree of synergism was greater for the morphine-thiopental combination; the maximal deviation from additive interaction was 2.27 (P < 0.001). Comparison of the results with the outcomes of opioid-barbiturate interactions in relation to blockade of purposeful movement response to tail clamping, which was antagonistic, shows that the combination of a barbiturate with an opioid gives different outcomes for different end-points of anesthesia. This suggests that the anesthetic effect of an agent is composed of several components, each with a different mechanism of action.
Hepatic Effects of Repeated Halothane Anesthetics in the Hypoxic Rat Model
Authors: Plummer John L. , Hall Pauline de la M. , Jenner Mark A. , Cousins Michael J.
Published: September 2006

The hepatic effects of repeated anesthesia of phenobarbital-induced Fischer 344 rats with 1% halothane/14% oxygen were investigated, after anesthetics were administered at either 1-day or 5-day intervals. Urinary excretion of fluoride, a product of reductive halothane metabolism, was increased in the 24-h period following anesthesia, but was the same after the first, second, and third anesthetics. Rats killed 24 h after a single anesthetic all had centrilobular hepatocellular necrosis. All animals killed 24 h after the second or third anesthetic also had centrilobular necrosis, but, in most animals, this was no more extensive than that following a single anesthetic, regardless of whether the interval between anesthetics was one or five days.
Altered dynamics in Lck SH3 upon binding to the LBD1 domain of Herpesvirus saimiri Tip
Authors: Weis David D. , Kjellen Peter , Sefton Bartholomew M. , Engen John R.
Published: September 2006

The Tip protein from Herpesvirus saimiri interacts with the SH3 domain from the Src‐family kinase Lck via a proline‐containing sequence termed LBD1. Src‐family kinase SH3 domains related to Lck have been shown to be dynamic in solution and partially unfold under physiological conditions. The rate of such partial unfolding is reduced by viral protein binding. To determine if the Lck SH3 domain displayed similar behavior, the domain was investigated with hydrogen exchange and mass spectrometry. Lck SH3 was found to be highly dynamic in solution. While other SH3 domains require as much as 10,000 sec to become totally deuterated, Lck SH3 became almost completely labeled within 200 sec. A partial unfolding event involving 8–10 residues was observed with a half‐life of ∼10 sec. Tip LBD1 binding did not cause gross structural changes in Lck SH3 but globally stabilized the domain and reduced the rate of partial unfolding by a factor of five. The region of partial unfolding in Lck SH3 was found to be similar to that identified for other SH3 domains that partially unfold. Although the sequence conservation between Lck SH3 and other closely related SH3 domains is high, the dynamics do not appear to be conserved.
Methods for the accurate estimation of confidence intervals on protein folding φ‐values
Authors: Ruczinski Ingo , Sosnick Tobin R. , Plaxco Kevin W.
Published: September 2006

φ‐Values provide an important benchmark for the comparison of experimental protein folding studies to computer simulations and theories of the folding process. Despite the growing importance of φ measurements, however, formulas to quantify the precision with which φ is measured have seen little significant discussion. Moreover, a commonly employed method for the determination of standard errors on φ estimates assumes that estimates of the changes in free energy of the transition and folded states are independent. Here we demonstrate that this assumption is usually incorrect and that this typically leads to the underestimation of φ precision. We derive an analytical expression for the precision of φ estimates (assuming linear chevron behavior) that explicitly takes this dependence into account. We also describe an alternative method that implicitly corrects for the effect. By simulating experimental chevron data, we show that both methods accurately estimate φ confidence intervals. We also explore the effects of the commonly employed techniques of calculating φ from kinetics estimated at non‐zero denaturant concentrations and via the assumption of parallel chevron arms. We find that these approaches can produce significantly different estimates for φ (again, even for truly linear chevron behavior), indicating that they are not equivalent, interchangeable measures of transition state structure. Lastly, we describe a Web‐based implementation of the above algorithms for general use by the protein folding community.
Intrathecal donor lymphocyte infusion for the treatment of suspected refractory lymphomatous meningitis: a case report
Authors: Meuleman N. , Ahmad I. , Duvillier H. , Lemort M. , Bennani J. , Martiat M. , Lagneaux L. , Bron D.
Published: September 2006

Abstract:  A 43‐year‐old female with large T‐cell non‐Hodgkin's lymphoma and central nervous system (CNS) involvement underwent HLA‐identical‐sibling peripheral blood stem cell transplantation (SCT) during her third complete remission. She presented a possible refractory CNS relapse 5 months after the transplant. She was then treated with intrathecal (IT) donor lymphocyte infusions (DLI). No side effects were observed after three DLI injections. The patient died 13 months later from infectious complications with no evidence of progressive disease. To our knowledge, this is the first case report of IT DLI for possible refractory lymphomatous meningitis.
A phase I radioimmunolocalization trial of humanized monoclonal antibody huA33 in patients with gastric carcinoma
Authors: Sakamoto Junichi , Oriuchi Noboru , Mochiki Erito , Asao Takayuki , Scott Andrew M. , Hoffman Eric W. , Jungbluth Achim A. , Matsui Takanori , Lee F. T. , Papenfuss Anthony , Kuwano Hiroyuki , Takahashi Toshitada , Endo Keigo , Old Lloyd J.
Published: September 2006

In order to determine the in vivo characteristics of huA33, an open label dose escalation biopsy‐based phase I clinical trial and radioimmunolocalization study were conducted with a complement determinant region‐grafted humanized monoclonal antibody against the A33 antigen in patients with gastric carcinoma. Thirteen patients were entered onto one of four dose levels (1.0, 2.0, 5.0 or 10.0 mg/m2). Patients with locally advanced (UICC‐TNM [International Union Against Cancer–tumor, node, metastasis] stage over 2 but resectable at clinical diagnosis) gastric carcinoma received a single infusion of 131I‐huA33 1 week prior to surgery. Adverse events were monitored, and imaging studies with gamma camera plus ex vivo scintigraphy of the resected specimen, biodistribution study by dosimetry analysis of the biopsied and resected tissues, and immunohistochemical analysis were carried out and evaluated. No dose‐limiting toxicity was observed during the trial. Therefore, the maximum tolerated dose was not reached. Although cancer tissues with + intensity and <25% extent by immunostaining in biopsied frozen sections did not show positive imaging or postoperative dosimetry findings, cancers with ++ or +++ intensity or wide (>25%) extent by frozen and paraffin sections in the biopsied specimen showed positive ex vivo tumor images and positive antigen expression in resected gastric cancer specimens, and the biodistribution analysis showed tumor uptake of 131I‐huA33. In conclusion, humanized monoclonal antibody huA33 demonstrated selective localization to gastric cancer that expressed A33 antigen strongly. These excellent targeting characteristics of huA33 indicate potential for targeted therapy of advanced gastric cancer that is refractory to cytotoxic therapy, and could also be exploitable for curatively resected early gastric cancer in an adjuvant setting. (Cancer Sci 2006; 97: 1248–1254)
Protein kinase A subunits of the ascomycete pathogen Mycosphaerella graminicola regulate asexual fructification, filamentation, melanization and osmosensing
Authors: MEHRABI RAHIM , KEMA GERT H. J.
Published: September 2006

As in many fungi, asexual reproduction of Mycosphaerella graminicola in planta is a complex process that requires proper differentiation of the infectious hyphae in the substomatal cavities of foliar tissue before pycnidia with conidia can be formed. In this study, we have investigated the role of the cAMP signalling pathway in development and pathogenicity of this pathogen by disruption of the genes encoding the catalytic (designated MgTpk2) and regulatory subunit (designated MgBcy1) of protein kinase A. The MgTpk2 and MgBcy1 mutants showed altered phenotypes in vitro when grown under different growth conditions. On potato dextrose agar (PDA), MgBcy1 mutants showed altered osmosensitivity and reduced melanization, whereas the MgTpk2 mutants showed accelerated melanization when compared with the M. graminicola IPO323 wild‐type strain and ectopic transformants. MgTpk2 mutants also secreted a dark‐brown pigment into yeast glucose broth medium. In germination and microconidiation assays, both mutants showed a germination pattern similar to that of the controls on water agar, whereas on PDA filamentous growth of MgTpk2 mutants was impaired. Pathogenicity assays showed that the MgTpk2 and MgBcy1 mutants were less virulent as they caused only limited chlorotic and necrotic symptoms at the tips of the inoculated leaves. Further analyses of the infection process showed that MgTpk2 and MgBcy1 mutants were able to germinate, penetrate and colonize mesophyll tissue, but were unable to produce the asexual fructifications, which was particularly due to inappropriate differentiation during the late stage of this morphogenesis‐related process.
Resistance to fracture of roots filled with three different techniques
Authors: Sagsen B. , Er O. , Kahraman Y. , Akdogan G.
Published: September 2006

Aim  To compare the fracture resistance of roots filled with different materials.

Methodology  Thirty‐four freshly extracted human maxillary central incisor teeth with similar dimension were selected. Crowns were sectioned at the cemento‐enamel junction, and the length of the roots were adjusted to 13 mm. Following the preparation of the root canals and final irrigation with EDTA and saline, the 10 root canals in group 1 were filled with Resilon cones and Epiphany sealer, the 10 root canals in group 2 were filled with gutta‐percha and AH 26 and the 10 root canals in group 3 were filled with gutta‐percha and MCS Canal Sealer. All materials were used with a cold lateral condensation technique. Four root canals remained unfilled and were used as a control group. Tests for fracture strength were performed using a universal testing machine and a round tip that had a diameter of 4 mm. The force was applied vertically with a constant speed of 1 mm min−1. For each root, the force at the time of fracture was recorded in Newtons. Results were evaluated statistically with anova and Tukey Honestly Significant Difference (HSD) tests.

Results  The mean force of fracture values was 1043 N, 967 N, 859 N and 517.5 N for groups 3, 1 and 2 and the control group, respectively. There was a significant difference (P < 0.01) between the experimental groups and the control group. No significant differences were found between the three experimental groups.

Conclusions  All the materials used in the present study reinforced the prepared root canals.
Fragmentation, disturbance and tree diversity conservation in tropical montane forests
Authors: CAYUELA LUIS , GOLICHER DUNCAN J. , BENAYAS JOSÉ MARÍA REY , GONZÁLEZ‐ESPINOSA MARIO , RAMÍREZ‐MARCIAL NEPTALÍ
Published: September 2006

Loss in forest cover associated with human activities leads to forest islands within a fragmented landscape. Anthropogenic disturbance may also directly alter tree species diversity. Habitat fragmentation and disturbance may have implications for biodiversity conservation and can affect a variety of population and community processes over a range of temporal and spatial scales. Effects are manifest both within and between fragments. The complexity of this process challenges the predictive value of simple models based on island biogeographical theory.

We analysed data on tree species diversity from 195 field plots in 16 tropical montane forest fragments in the Highlands of Chiapas, Mexico. Within this area we identified five community types. Variation in species diversity between fragments in each community was analysed by fitting linear models in which area, core area, edge/area ratio, and mean proximity index were related to mean plot diversity. Variations within fragments were then analysed using linear mixed‐effects models in which the fixed effects were considered to be proximity to edge, canopy closure and a degradation index, whereas fragment‐level variation was modelled as a random effect.

Effects of fragmentation per se, defined as the reduction in area and connectivity between fragments, were not detectable. Within‐fragment effects, however, were evident. Disturbance was associated with lower tree diversity at a local scale, and a notable impact on late successional species.

While not statistically detectable, we expected fragmentation per se to be acting to reduce diversity in the long term. We therefore complemented our analysis by calculating the theoretical loss in species when the number of tree stems in a fragment was halved for each community type using resampled accumulation curves. These models predicted a maximum loss in transitional forest (12 species lost) and evergreen cloud forest fragments (seven to nine species lost) and a minimum loss in oak forest fragments (three species lost).

Synthesis and applications. Our results call into question the utility of island theory when setting conservation priorities for tree species. In our study region, and elsewhere, tree diversity is most immediately threatened by the effects of within‐fragment disturbance. The few remaining areas of intact native forests should be prioritized for conservation regardless of their size and connectivity. If diversity is conserved within these fragments, the short‐term effects of landscape‐scale change may be minimized. They may then be reversed if long‐term restoration initiatives can be implemented.
Increased levels of KL‐6 and subsequent mortality in patients with interstitial lung diseases
Authors: SATOH H. , KURISHIMA K. , ISHIKAWA H. , OHTSUKA M.
Published: September 2006

Abstracts.

Objectives.  KL‐6 is a specific marker in patients with interstitial lung diseases (ILDs); however, the relationship between elevated levels of KL‐6 and subsequent mortality is not well defined. To determine if elevated serum levels of KL‐6 are associated with increased mortality, and to identify the most suitable cut‐off level of KL‐6 by which to distinguish between good prognosis and poor prognosis, we evaluated the prognostic significance of serum KL‐6 levels in patients with stable‐state ILDs.

Methods.  Two hundred and nineteen patients diagnosed with ILDs (152 with idiopathic interstitial pneumonia and 67 with collagen disease‐associated pulmonary fibrosis) at Tsukuba University Hospital from April 1999 to October 2005 were entered in this study. Serum KL‐6 levels in patients with ILDs were measured with a commercially available enzyme immunoassay kit, and these patients were then followed up.

Results.  During the follow‐up period, 58 of the 219 patients died of respiratory failure. Patients who died during this period had higher levels of KL‐6 than did those who did not (P = 0.0004). The receiver operating characteristic curve analysis showed 1000 U mL−1 as the most suitable cut‐off level by which to distinguish between the two groups of patients. The 95% specificity serum KL‐6 level with poor outcome was 2750 U mL−1. In univariate and multivariate analysis, elevated serum KL‐6 (>1000 U mL−1) in the stable state indicated poor prognosis (P = 0.0005, log‐rank test; P = 0.0001, Cox proportional hazard model).

Conclusions.  Elevated KL‐6 level may provide simple, yet valuable information by which to identify patients with ILDs who are at increased risk for subsequent mortality.
Characteristics and outcome amongst young adults suffering from out‐of‐hospital cardiac arrest in whom cardiopulmonary resuscitation is attempted
Authors: HERLITZ J. , SVENSSON L. , SILFVERSTOLPE J. , ÄNGQUIST K.‐A. , WISTEN A. , ENGDAHL J. , HOLMBERG S.
Published: September 2006

Objectives.  Amongst patients suffering from out‐of‐hospital cardiac arrest, young adults represent a minority. However, these victims suffer from the catastrophe when they are in a very active phase of life and have a long life expectancy. This survey aims to describe young adults in Sweden who suffer from out‐of‐hospital cardiac arrest and in whom cardiopulmonary resuscitation (CPR) is attempted in terms of characteristics and outcome.

Design.  Prospective and descriptive design.

Subjects and methods.  Young adults (18–35 years) who suffered from out‐of‐hospital cardiac arrest in whom CPR was attempted and who were included in the Swedish Cardiac Arrest Registry between 1990 and 2004.

Main outcome measures.  Survival to 1 month.

Results.  In all, 1105 young adults (3.1% of all the patients in the registry) were included, of which 29% were females, 51% were nonwitnessed and 15% had a cardiac aetiology. Only 17% were found in ventricular fibrillation, 53% received bystander CPR. The overall survival to 1 month was 6.3%. High survival was found amongst patients found in ventricular fibrillation (20.8%) and those with a cardiac aetiology (14.8%). Ventricular fibrillation at the arrival of the rescue team remained an independent predictor of an increased chance of survival (odds ratio: 7.43; 95% confidence interval: 3.44–16.65).

Conclusion.  Amongst young adults suffering from out‐of‐hospital cardiac arrest and in whom CPR was attempted, a minority survived to 1 month. Subgroups with a higher survival could be defined (patients found in ventricular fibrillation and patients in whom there was a cardiac aetiology). However, only one independent predictor of an increased chance of survival could be demonstrated, i.e. ventricular fibrillation at the arrival of the rescue team.
Loss of Hfq activates the σE‐dependent envelope stress response in Salmonella enterica
Authors: Figueroa‐Bossi Nara , Lemire Sébastien , Maloriol Danièla , Balbontín Roberto , Casadesús Josep , Bossi Lionello
Published: September 2006

Ubiquitous RNA‐binding protein Hfq mediates the regulatory activity of many small RNAs (sRNAs) in bacteria. To identify potential targets for Hfq‐mediated regulation in Salmonella, we searched for lacZ translational fusions whose activity varied in the presence or absence of Hfq. Fusions downregulated by Hfq were more common than fusions showing the opposite response. Surprisingly, in a subset of isolates from the major class, the higher activity in the absence of Hfq was due to transcriptional activation by the alternative sigma factor RpoE (σE). Activation of the σE regulon normally results from envelope stress conditions that elicit proteolytic cleavage of the anti‐σE factor RseA. Using an epitope tagged variant of RseA, we found that RseA is cleaved at an increased rate in a strain lacking Hfq. This cleavage was dependent on the DegS protease and could be completely prevented upon expressing the hfq gene from an inducible promoter. Thus, loss of Hfq function appears to affect envelope biogenesis in a way that mimics a stress condition and thereby induces the σE response constitutively. In a RseA mutant, activation of the σE response causes Hfq‐dependent downregulation of outer membrane protein (OMP) genes including lamB, ompA, ompC and ompF. For ompA, downregulation results in part from σE‐dependent accumulation of MicA (SraD), a small RNA recently shown to downregulate ompA transcript levels in stationary phase. We show that the micA gene is under σE control, and that DegS‐mediated σE release is required for the accumulation of MicA RNA upon entry into stationary phase. A similar mechanism involving additional, still unidentified, sRNAs, might underlie the growth phase‐dependent regulation of other OMP mRNAs.