bluuebunny/crossref_metadata_2025 huggingface dataset:
IS INCOMPARABILITY A PROBLEM FOR ANYONE?
Authors: HSIEH NIEN-HÊ
Published: April 2007

The incomparability of alternatives is thought to pose a problem for justified choice, particularly for proponents ofcomparativism– the view that comparative facts about alternatives determine what one rationally ought to choose. As a solution, it has been argued that alternatives judged incomparable by one of the three standard comparative relations, “better than,” “worse than,” and “equally good,” are comparable by some fourth relation, such as “roughly equal” or “on a par.” This solution, however, comes at what many would regard as too high a cost – namely, rejection of the transitivity of the relation “at least as good as.” In this paper, I argue that proponents of comparativism need not incur this cost. I defend the possibility of justified choice between incomparable alternatives on grounds that comparativists can accept. The possibility of incomparability has been met with resistance, in part because of the intuitive appeal of comparativism. By defending the possibility of justified choice between incomparable alternatives on grounds that comparativists can accept, this paper supports further inquiry into the subject of incomparability.
THE GOOD, THE BAD, AND THE ETHICALLY NEUTRAL
Authors: BYKVIST KRISTER
Published: April 2007

John Broome's Weighing Lives provides a much-needed framework for the intriguing problems of population ethics. It is also an impressive attempt to find a workable solution to these problems. I am not sure that Broome has found the right solution, but I think he has done the ethics profession a tremendous service in tidying up the discussion. The framework he presents will make it possible for the participants in this debate to formulate their positions in a clear and precise manner. Even people who disagree with him will be helped by this framework, since they will now be able to show exactly where their views differ.
THE PARITY VIEW AND INTUITIONS OF NEUTRALITY
Authors: QIZILBASH MOZAFFAR
Published: April 2007

One response to Derek Parfit's ‘mere addition paradox’ invokes the relation of ‘parity’. Since parity is a form of ‘incommensurateness’ in John Broome's terms, three doubts which Broome raises about accounts involving incommensurateness in Weighing Lives pose a challenge for this response. I discuss two of these. They emerge from a discussion of various intuitions about ‘neutrality’. I argue that an account based on parity may be no less consistent with Broome's intuitions than is his own vagueness view.
The rationale for and the current role of chemoradiotherapy
Authors: Prestwich R. J. , Shakespeare D. , Waters S.
Published: April 2007

Combined-modality treatment using chemotherapy and radiotherapy, particularly concurrently, has now become the standard of care for many solid tumour sites on the basis of improvements in locoregional disease control and in some cases survival. The rationale for combined-modality treatment, potential mechanisms of interaction, the therapeutic ratio and the current place of sequential and concurrent chemoradiotherapy are discussed.
Research or reality: Within the context of UK radiotherapy and cancer services, where should research and investment be focused to best improve UK treatment outcomes?
Authors: O'Connell O.F.D.
Published: April 2007

Purpose: It is now six years since the publication of the NHS Cancer Plan. During this time, there has been considerable investment and research within UK cancer services. Some progress has been made towards improving treatment outcomes, but obstacles persist. This article explores some recent advances in cancer treatment and considers whether UK cancer treatment outcomes will best improve through the clinical advances being made in cancer research or whether improvement now needs to be more explicitly driven via a strategic approach.Methodology: The article explores this question from two differing perspectives. First, from a research perspective, it reviews briefly the evidence for a selection of clinical advancements in cancer therapy that have all been cited as providing breakthroughs in treatment outcomes. Second, it considers the investment in cancer research within a more strategic context, focusing on the reality of managing an improvement programme in UK cancer services. Here, some of the practical obstacles to improving treatment outcomes are highlighted.Findings: Significant progress has been made over the past six years towards improving UK treatment outcomes. Much of this is a direct result of international advances in clinical research. Further progress, however, is required. This article argues that progress will best be achieved by focusing resources and research investment on tackling some of the endemic strategic obstacles, highlighted in this article, that are the present reality within UK cancer services.
“Category-Split” Effekte bei Urteilen über Sportlerinnen, Sportler und Sportarten
Authors: Unkelbach Christian , Plessner Henning
Published: April 2007

Zusammenfassung: Nach dem Stichprobenansatz ( Fiedler, 2000 ) entstehen viele Urteilsfehler nicht unbedingt durch kognitive Defizite, sondern durch den Prozess des Sammelns von Informationen. Die daraus resultierende Informationsstichprobe kann aus vielerlei Gründen unzulänglich oder verzerrt sein, wobei Menschen sich dieser Verzerrungen und Unzulänglichkeiten in der Regel nicht bewusst sind. Wir präsentieren drei Experimente, bei denen sowohl ausgebildete Trainerinnen und Trainer als auch Studierende eine fehlende Sensibilität für Manipulationen der Informationsstichprobe zeigten. Die Aufgabe bestand darin, entweder einen Fußballspieler (Exp. 1 & 3) oder verschiedene Sportarten (Exp. 2) aufgrund von erinnerten Informationen zu bewerten. Dabei wurde die Menge an positiver und negativer Informationen in den subjektiven Gedächtnisstichproben durch “Category-Split” ( Fiedler & Armbruster, 1994 ) und die Abrufleichtigkeit ( Schwarz et al., 1991 ) manipuliert. Die Urteile spiegelten die Information in den Gedächtnisstichproben wieder, d. h. die offensichtlichen Verzerrungen wurden nicht korrigiert. Die Implikationen dieser Befunde für Bewertungen im Sport und die Sportberichterstattung werden diskutiert.
Fairness oder Fouls
Authors: Hoffmann Andreas
Published: April 2007

Zusammenfassung: Die Bereitschaft, sich fair zu verhalten, scheint gerade in sportlichen Wettkampfsituationen von situativen Einflüssen und widersprüchlichen sozialen Erwartungen beeinflusst zu werden. Im Sinne der normative focus theory von Cialdini, Kallgren und Reno (1991) rückt die Orientierung an der Norm der Fairness unter situativen Gegebenheiten unter Umständen in den Hintergrund. Wie jugendliche Sportler mit Normkonflikten und Situationseinflüssen umgehen und welche Rolle hierbei Trainer/innen als Vorbilder spielen, wurde bislang kaum untersucht. In einer Fragebogenstudie mit 547 Fußballern (9-18 Jahre) zeigt sich die Bereitschaft zu foulen von situativen Bedingungen (z. B. Zuschauerdruck, Abstiegsdrohung) und wahrgenommenen Trainernormen beeinflusst. Den Trainern schreiben die Jugendlichen zu, dass sie Fouls weitgehend tolerieren. Bezogen auf Gemeinnützigkeitsansprüche der Sportvereine legen diese Befunde eine intensivere Debatte der Vorbildfunktion von Trainern nahe.
Umgang mit fehlenden Werten in der psychologischen Forschung
Authors: Lüdtke Oliver , Robitzsch Alexander , Trautwein Ulrich , Köller Olaf
Published: April 2007

Zusammenfassung. Fehlende Werte stellen in der empirisch-psychologischen Forschung oftmals ein Problem dar. Häufig verwendete Verfahren wie fallweiser und paarweiser Ausschluss, Regression- und Mean-Imputation sind aus methodischer Sicht defizitär. Alternative Verfahren für die Analyse von Datensätzen mit fehlenden Werten, die in den letzten drei Jahrzehnten entwickelt wurden, werden in der Forschungspraxis noch selten angewendet. Der vorliegende Beitrag führt zunächst in die grundlegende Terminologie fehlender Werte nach Rubin (1976) ein. Im Anschluss daran wird eine Übersicht der in der Literatur diskutierten Ansätze zum Umgang mit fehlenden Werten vorgenommen, wobei drei Typen von Verfahren unterschieden werden: klassische Verfahren (z.B. fallweiser Ausschluss), imputationsbasierte Verfahren, in denen fehlende Werte ersetzt (imputiert) werden, und modellbasierte Verfahren, in denen die Schätzung des Modells und die Behandlung der fehlenden Werte in einem Schritt vorgenommen werden. Anhand eines Datenbeispiels wird dann der Einsatz der Multiplen Imputation veranschaulicht. Abschließend werden Implikationen für die Forschungspraxis diskutiert.
Sulfur dioxide emissions from Peruvian copper smelters detected by the Ozone Monitoring Instrument
Authors: Carn S. A. , Krueger A. J. , Krotkov N. A. , Yang K. , Levelt P. F.
Published: April 2007

We report the first daily observations of sulfur dioxide (SO2) emissions from copper smelters by a satellite‐borne sensor ‐ the Ozone Monitoring Instrument (OMI) on NASA's EOS/Aura spacecraft. Emissions from two Peruvian smelters (La Oroya and Ilo) were detected in up to 80% of OMI overpasses between September 2004 and June 2005. SO2 production by each smelter in this period is assessed and compared with contemporaneous emissions from active volcanoes in Ecuador and southern Colombia. Annual SO2 discharge from the Ilo smelter, La Oroya smelter, and volcanoes in 2004–2005 is estimated and amounts to 0.3−0.1+0.2, 0.07 ± 0.03, and 1.2 ± 0.5 Tg, respectively. This study confirms OMI's potential as an effective tool for evaluation of anthropogenic and natural SO2 emissions. Smelter plumes transport an array of toxic metals in addition to SO2 and continued monitoring to mitigate health and environmental impacts is recommended.
Submarine gas burst at Panarea Island (southern Italy) on 3 November 2002: A magmatic versus hydrothermal episode
Authors: Capaccioni Bruno , Tassi Franco , Vaselli Orlando , Tedesco Dario , Poreda Robert
Published: April 2007

On 3 November 2002, fishermen observed the sudden appearance at the sea surface of three large whitish plumes 3 km offshore of Panarea Island (Aeolian Islands, southern Italy) caused by the uprising from the seafloor of huge columns of gas bubbles, mixed with sediments and colloidal sulfur. The degassing event partly superimposed an already existing gentle‐degassing fumarolic field. Since 12 November 2002, a discontinuous geochemical monitoring program of these new discharging fluids have been carried out. The submarine emissions collected on November 2002 were an emulsion made by a CO2‐dominated continuous gas phase with suspended sediments, colloidal sulfur, and water condensate microdroplets acidified by dissolution of compounds such as SO2, HCl, and HF. In the gas phase, light‐unsaturated hydrocarbons also occurred, possibly related to relatively high temperature and oxidizing conditions due to local input of magmatic fluids at depth, whose occurrence was also supported by the relative high values of 3He/4He isotopic ratio (R/Rair = 4.62) with respect to previously measured values (R/Rair < 4.2). The flux of the submarine emissions significantly decreased in a couple of months together with the almost complete disappearance of the magmatic chemical markers and the decrease of the helium isotopic ratio. Thus the most striking feature of the temporal and spatial evolution in the chemical and isotopic compositions of the submarine fumaroles was the relatively rapid restoration, since January 2003, of the precrisis conditions, i.e., typical of a stationary hydrothermal system.
Investigations of newly formed sea ice in the Cape Bathurst polynya: 1. Structural, physical, and optical properties
Authors: Ehn Jens K. , Hwang Byong Jun , Galley Ryan , Barber David G.
Published: April 2007

The physical, structural, and optical properties of newly formed ice types were studied in the Cape Bathurst polynya (71°N, 127°W) during fall freezeup in October to early November 2003. Variable meteorological conditions with occasional snowfall resulted in the formation of numerous ice types and surface conditions. Ice samples were collected from horizontally homogeneous surfaces representative of the area. Crystallographic analysis on 33 ice cores revealed highly variable growth conditions and formation mechanisms in the area. The mean fraction of granular ice was 33%, while intermediate granular‐columnar and columnar ice contributed 37% and 30%, respectively. Salinity profiles in the ice were C‐shaped and as the ice grew thicker, bulk salinities decreased according to 4.582 + 13.358/hi (cm). These conditions resulted in brine volumes ranging from 4% to 46%. Bare ice surfaces commonly formed a high salinity brine skim layer due to brine expulsion. Salinities up to 40‰ were observed in this layer. Under suitable conditions frost flowers formed on the ice, and their presence was related to characteristic ice microstructure with crystals that appeared disc‐like in shape. Fine‐grained snow‐ice was formed when snow merged with surface brine to create a complex hypersaline surface at the snow/ice interface. The spectral reflectance for the thin ice types was most strongly related to surface conditions. The presence of frost flowers significantly increased the reflectance independent of snow precipitation. Any increase in ice thickness was found to have little effect on the reflectance once a 20–30 mm thick snow layer was present.
Investigations of newly formed sea ice in the Cape Bathurst polynya: 2. Microwave emission
Authors: Hwang Byong Jun , Ehn Jens K. , Barber David G. , Galley Ryan , Grenfell Thomas C.
Published: April 2007

This study examines the role of newly formed sea ice geophysical state on microwave emission. Coincident with sea ice geophysical sampling, ship‐based passive microwave emission data (dual‐polarized at 19, 37 and 85 GHz) were collected in the Cape Bathurst Polynya during 18 October and 13 November 2003. Using polarization ratios (PRs), we found that bare thin ice was separable from snow‐covered ice. Thin snow (equal to 0.02–0.13 m) thickness is significantly correlated with the spectral gradient ratios GRV(85,19) (R2 = 0.55, P‐value <0.05) and GRV(85,37) (R2 = 0.66, P‐value < 0.05), but not with GRV(37,19) (R2 = 0.19, P‐value > 0.2). The relationship between atmospherically corrected R37 and bare ice thickness showed an exponential relationship very comparable to that reported by Martin et al. [2004], which is ascribed to the reduction of bare ice surface salinity based on both observational and modeling studies. However, the relationship quickly becomes invalid for even thin snow covered ice, due to significant impact of thin wet (liquid water fraction ∼0.02–0.04) snow on microwave emission. Our results suggest that the sea ice algorithms NASA Team and NASA Team 2 could underestimate total ice concentration over thin bare ice by 35% on average, while both algorithms underestimate the total ice concentration by 20% over snow‐covered ice. Using PR(85) sea ice could be delineated from open water using a properly adjusted threshold value accounting for cloud or fog effects, possibly with the exception of dark nilas and/or bare consolidated pancakes.
Late Quaternary variability of sedimentary nitrogen isotopes in the eastern South Pacific Ocean
Authors: De Pol‐Holz Ricardo , Ulloa Osvaldo , Lamy Frank , Dezileau Laurent , Sabatier Pierre , Hebbeln Dierk
Published: April 2007

We present high‐resolution bulk sedimentary δ15N data from the southern edge of the present‐day oxygen minimum zone of the eastern South Pacific. The record is interpreted as representing changes in water column nitrogen removal during the last 70,000 years. We found significant fluctuations in the isotopic signal that suggest major reorganizations of the oxygen minimum zone at millennial timescales. These fluctuations were not related to other millennial‐scale changes like the Northern Hemisphere's Dansgaard‐Oeschger climate swings or local changes in primary productivity, so appear to be dictated by the Southern Hemisphere's climate rhythm. This is preliminarily corroborated by an overall agreement between our δ15N data and the sedimentary proxy of ice sheet dynamics in Patagonia, which is in turn correlated with surface water properties at the midlatitude subduction region of the eastern South Pacific intermediate waters. Finally, potential implications on late Quaternary changes in atmospheric CO2 concentrations are discussed.
Radiocarbon age of late glacial deep water from the equatorial Pacific
Authors: Broecker Wallace , Clark Elizabeth , Barker Stephen , Hajdas Irena , Bonani Georges , Moreno Eva
Published: April 2007

Radiocarbon age differences for pairs of coexisting late glacial age benthic and planktic foraminifera shells handpicked from 10 sediment samples from a core from a depth of 2.8 km in the western equatorial Pacific are not significantly different from that of 1600 years calculated from measurements on prenuclear seawater. This places a lower limit on the depth of the interface for the hypothetical radiocarbon‐depleted glacial age seawater reservoir required to explain the 190‰ drop in the 14C/C for atmospheric CO2, which occurred during the mystery interval (17.5 to 14.5 calendar years ago). These measurements restrict the volume of this reservoir to be no more than 35% that of the ocean. Further, 14C measurements on a single Last Glacial Maximum age sample from a central equatorial Pacific core from a depth of 4.4 km water fail to reveal evidence for the required 5‐ to 7‐kyr age difference between benthic and planktic foraminifera shells if the isolated reservoir occupied only one third of the ocean. Nor does the 13C record for benthic forams from this abyssal core yield any evidence for the excess respiration CO2 expected to be produced during thousands of years of isolation. Nor, as indicated by the presence of benthic foraminifera, was the dissolved oxygen used up in this abyssal water.
Separating surface storage from hyporheic retention in natural streams using wavelet decomposition of acoustic Doppler current profiles
Authors: Phanikumar Mantha S. , Aslam Irfan , Shen Chaopeng , Long David T. , Voice Thomas C.
Published: April 2007

The ability to separate surface storage (e.g., due to in‐channel features such as eddies and pools) from retention due to hyporheic exchange is important in many solute transport considerations; however, current stream tracer approaches do not allow such separation. We examined transient storage processes in a fourth‐order Michigan stream using tracer studies, numerical flow and transport models, and hydrodynamic data obtained from acoustic Doppler current profiler (ADCP) surveys. Since the high‐resolution, three‐dimensional velocity fields obtained from an ADCP relate to in‐channel processes, we used wavelet decomposition to separate the flow into regions of slow and fast moving zones and to estimate the relative sizes of the main channel (A) and the storage zones (AS). Transport modeling based on the tracer data provided estimates of storage zone sizes that included contributions from both surface storage and hyporheic exchange. By coupling the estimates from tracer data with those obtained from an ADCP we were able to assess the relative importance of surface storage in different stream reaches. Estimated (AS/A) values in three test reaches ranged from 0.12 to 0.22, and transient storage residence times varied from approximately 4 min in a run reach dominated by surface storage (reach A) to about 13 min in a reach with some potential for hyporheic exchange (reach C). In reach A the (AS/A) values estimated from tracer and ADCP data were in good agreement, indicating that in‐channel processes were the main mechanism responsible for storage in this reach. Reach C estimates, however, showed that surface storage (AS/A = 0.05) accounted for only a fraction of the transient storage estimated using tracer data (AS/A = 0.12), which indicated that hyporheic exchange contributed to transient storage in the reach. The wavelet decomposition approach based on the ADCP data provides a framework to better constrain transient storage models and to eliminate unrealistic parameters.
Water balance variability at the interstorm timescale
Authors: Potter N. J. , Zhang L.
Published: April 2007

The translation of rainfall variability into variability in evapotranspiration, soil moisture, or runoff depends on many factors. Previously published results indicate that the sensitivity of evapotranspiration to rainfall at the interannual timescale generally increases as catchment aridity increases. This paper generalizes these results to the interstorm timescale by calculating the variance of interstorm evapotranspiration from a stochastic model of soil moisture balance. The derived analytical solution is compared to expressions for the variability of antecedent and poststorm soil moisture. This analysis shows that variability of interstorm evapotranspiration is low when average storm depth or average interstorm potential evapotranspiration is small relative to soil moisture capacity, as evapotranspiration is limited by the available water and energy. When water and energy inputs are larger, interstorm evapotranspiration variability is closely connected to variability in antecedent and poststorm soil moisture. The interstorm evapotranspiration deviation ratio is also calculated and compared to results from the interannual timescale. The effects of variable potential evapotranspiration and soil moisture controls on the rate of actual evapotranspiration are also considered.
Balance Theory, Unit Relations, and Attribution: The Underlying Integrity of Heiderian Theory
Authors: Crandall Christian S. , Silvia Paul J. , N'Gbala Ahogni Nicolas , Tsang Jo-Ann , Dawson Karen
Published: April 2007

Fritz Heider's theory of social perception is reviewed, and the close connection between attribution, balance, and unit relationship are examined, primarily through Heider's own writings. Attribution and balance have historically been considered separate theories, but the authors show how these two ideas, in conjunction with the idea of unit formation, create a broad-ranging and integrated theory of social perception. Attributions were seen by Heider as a particular kind of unit relationship, and people make attributions that preserve an affectively consistent view of others. The authors then show how this integrated understanding of Heider's ideas generates new predictions and informs a wide range of clinical, personality, and social psychological phenomena, as a reminder of the modern power of Heider's theory.
Toward a Cognitive Process Model of Ethnic/Racial Biases in Clinical Judgment
Authors: Whaley Arthur L. , Geller Pamela A.
Published: April 2007

The purpose of the present article is to discuss approaches to the development of cognitive process models of misdiagnosis of African Americans, with particular emphasis on structured clinical interviews. Two basic approaches to cognitive process models are discussed. The first is cognitive bias based on prototype models of information processing. The second approach involves using the structured clinical interview to see how and when the decision-making process may be flawed, or where cognitive shifts are made in considering one diagnosis over another. Although routine training in structured clinical interviews may nullify cognitive biases associated with clinician judgment, it does not address cultural biases in the diagnostic system. It is concluded that a comprehensive approach to training in clinical decision making for mental health professionals is needed which include courses in the administration of the Structured Clinical Interview for DSM-IV, sociocultural case formulation, and cross-cultural sensitivity in making psychodiagnostic judgments.
Population pharmacokinetic modelling of non‐linear brain distribution of morphine: influence of active saturable influx and P‐glycoprotein mediated efflux
Authors: Groenendaal D , Freijer J , de Mik D , Bouw M R , Danhof M , de Lange E C M
Published: April 2007

Background and purpose:

Biophase equilibration must be considered to gain insight into the mechanisms underlying the pharmacokinetic‐pharmacodynamic (PK‐PD) correlations of opioids. The objective was to characterise in a quantitative manner the non‐linear distribution kinetics of morphine in brain.

Experimental approach:

Male rats received a 10‐min infusion of 4 mg kg−1of morphine, combined with a continuous infusion of the P‐glycoprotein (Pgp) inhibitor GF120918 or vehicle, or 40 mg kg−1morphine alone. Unbound extracellular fluid (ECF) concentrations obtained by intracerebral microdialysis and total blood concentrations were analysed using a population modelling approach.

Key results:

Blood pharmacokinetics of morphine was best described with a three‐compartment model and was not influenced by GF120918. Non‐linear distribution kinetics in brain ECF was observed with increasing dose. A one compartment distribution model was developed, with separate expressions for passive diffusion, active saturable influx and active efflux by Pgp. The passive diffusion rate constant was 0.0014 min−1. The active efflux rate constant decreased from 0.0195 min−1to 0.0113 min−1in the presence of GF120918. The active influx was insensitive to GF120918 and had a maximum transport (Nmax/Vecf) of 0.66 ng min−1ml−1and was saturated at low concentrations of morphine (C50=9.9 ng ml−1).

Conclusions and implications:

Brain distribution of morphine is determined by three factors: limited passive diffusion; active efflux, reduced by 42% by Pgp inhibition; low capacity active uptake. This implies blood concentration‐dependency and sensitivity to drug‐drug interactions. These factors should be taken into account in further investigations on PK‐PD correlations of morphine.

British Journal of Pharmacology(2007)151, 701–712; doi:10.1038/sj.bjp.0707257
Influence of biophase distribution and P‐glycoprotein interaction on pharmacokinetic‐pharmacodynamic modelling of the effects of morphine on the EEG
Authors: Groenendaal D , Freijer J , de Mik D , Bouw M R , Danhof M , de Lange E C M
Published: April 2007

Background and purpose:

The aim was to investigate the influence of biophase distribution including P‐glycoprotein (Pgp) function on the pharmacokinetic‐pharmacodynamic correlations of morphine's actions in rat brain.

Experimental approach:

Male rats received a 10‐min infusion of morphine as 4 mg kg−1, combined with a continuous infusion of the Pgp inhibitor GF120918 or vehicle, 10 or 40 mg kg−1. EEG signals were recorded continuously and blood samples were collected.

Key results:

Profound hysteresis was observed between morphine blood concentrations and effects on the EEG. Only the termination of the EEG effect was influenced by GF120918. Biophase distribution was best described with an extended catenary biophase distribution model, with a sequential transfer and effect compartment. The rate constant for transport through the transfer compartment (k1e) was 0.038 min−1, being unaffected by GF120918. In contrast, the rate constant for the loss from the effect compartment (keo) decreased 60% after GF120918. The EEG effect was directly related to concentrations in the effect compartment using the sigmoidal Emaxmodel. The values of the pharmacodynamic parameters E0, Emax, EC50and Hill factor were 45.0 μV, 44.5 μV, 451 ng ml−1and 2.3, respectively.

Conclusions and implications:

The effects of GF120918 on the distribution kinetics of morphine in the effect compartment were consistent with the distribution in brain extracellular fluid (ECF) as estimated by intracerebral microdialysis. However, the time‐course of morphine concentrations at the site of action in the brain, as deduced from the biophase model, is distinctly different from the brain ECF concentrations.

British Journal of Pharmacology(2007)151, 713–720; doi:10.1038/sj.bjp.0707258
The plasma membrane Na+/Ca2+exchange inhibitor KB‐R7943 is also a potent inhibitor of the mitochondrial Ca2+uniporter
Authors: Santo‐Domingo J , Vay L , Hernández‐SanMiguel E , Lobatón C D , Moreno A , Montero M , Alvarez J
Published: April 2007

Background and purpose:

The thiourea derivative KB‐R7943, originally developed as inhibitor of the plasma membrane Na+/Ca2+exchanger, has been shown to protect against myocardial ischemia‐reperfusion injury. We have studied here its effects on mitochondrial Ca2+fluxes.

Experimental approach.

[Ca2+] in cytosol, mitochondria and endoplasmic reticulum (ER), and mitochondrial membrane potential were monitored using both luminescent (targeted aequorins) and fluorescent (fura‐2, tetramethylrhodamine ethyl ester) probes in HeLa cells.

Key results:

KB‐R7943 was also a potent inhibitor of the mitochondrial Ca2+uniporter (MCU). In permeabilized HeLa cells, KB‐R7943 inhibited mitochondrial Ca2+uptake with a Ki of 5.5±1.3 μM (mean±S.D.). In intact cells, 10μM KB‐R7943 reduced by 80% the mitochondrial [Ca2+] peak induced by histamine. KB‐R7943 did not modify the mitochondrial membrane potential and had no effect on the mitochondrial Na+/Ca2+exchanger. KB‐R7943 inhibited histamine‐induced ER‐Ca2+release in intact cells, but not in cells loaded with a Ca2+‐chelator to damp cytosolic [Ca2+] changes. Therefore, inhibition of ER‐Ca2+‐release by KB‐R7943 was probably due to the increased feedback Ca2+‐inhibition of inositol 1,4,5‐trisphosphate receptors after MCU block. This mechanism also explains why KB‐R7943 reversibly blocked histamine‐induced cytosolic [Ca2+] oscillations in the same range of concentrations required to inhibit MCU.

Conclusions and Implications:

Inhibition of MCU by KB‐R7943 may contribute to its cardioprotective activity by preventing mitochondrial Ca2+‐overload during ischemia‐reperfusion. In addition, the effects of KB‐R7943 on Ca2+homeostasis provide new evidence for the role of mitochondria modulating Ca2+‐release and regenerative Ca2+‐oscillations. Search for permeable and selective MCU inhibitors may yield useful pharmacological tools in the future.

British Journal of Pharmacology(2007)151, 647–654; doi:10.1038/sj.bjp.0707260
Endothelium‐independent constriction of isolated, pressurized arterioles by Nω‐nitro‐L‐arginine methyl ester (L‐NAME)
Authors: Murphy T V , Kotecha N , Hill M A
Published: April 2007

Background and purpose:

Nitric oxide synthase (NOS) inhibitors cause vasoconstriction in pressurized arterioles with myogenic tone. This suggests either tonic production of NO modulates myogenic tone or a direct, NOS‐independent effect of the NOS inhibitors. The nature of the contractile effect of the nitric oxide synthase inhibitor Nω‐nitro‐L‐arginine methyl ester (L‐NAME, 100 μM) on pressurised arterioles was investigated.

Experimental approach:

Segments of rat cremaster muscle first‐order arteriole were cannulated on glass micropipettes and maintained at an intraluminal pressure of 50, 70 or 120 mmHg.

Key results:

L‐NAME and the related compound L‐NA (100 μM) constricted pressurized vessels with myogenic tone. Removal of the endothelium did not cause constriction or alter myogenic tone, however the constrictor effect of L‐NAME persisted. The constrictor effect of L‐NAME was abolished by L‐arginine (1 mM). Other NO and cGMP pathway inhibitors, including the nNOS inhibitor 7‐nitroindazole (100 μM), the NO scavenger carboxy‐PTIO (100 μM), the guanylate cyclase inhibitor ODQ (10 μM) and the cGMP inhibitor Rp‐8CPT‐cGMPS (10 μM) did not cause constriction of the arterioles. L‐NAME caused a small (3‐4 mV) but not statistically significant depolarization of the arteriolar smooth muscle at both pressures. The constrictor effect was not prevented by the K+‐channel antagonist tetraethyl ammonium (TEA, 1 mM) or the KATP channel antagonist glibenclamide (1 μM).

Conclusions and implications:

These observations demonstrate that L‐NAME causes an endothelium‐ and NOS‐independent contraction of vascular smooth muscle in isolated skeletal muscle arterioles. It is suggested that the underlying mechanism relates to an arginine binding interaction.

British Journal of Pharmacology (2007) 151, 602–609; doi:10.1038/sj.bjp.0707262
Cryptotanshinone inhibits chemotactic migration in macrophages through negative regulation of the PI3K signaling pathway
Authors: Don M‐J , Liao J‐F , Lin L‐Y , Chiou W‐F
Published: April 2007

Background and purpose:

Cryptotanshinone, the major tanshinone isolated fromSalvia miltiorrhizaBunge, exhibits anti‐inflammatory activity. However, there is no report on the effect of cryptotanshinone on recruitment of leukocytes to inflammatory sites. We therefore assessed the effects of cryptotanshinone on macrophage chemotaxis.

Experimental approach:

Macrophage migration induced by complement 5a (C5a) or macrophage inflammatory protein‐1α (MIP‐1α) was measuredin vitro. Intracellular kinase translocation and phosphorylation was assessed by Western blotting.

Key results:

RAW264.7 cell migration towards C5a (1μg ml−1) was significantly inhibited by cryptotanshinone (1, 3, 10 and 30 μM) in a concentration‐dependent manner. Primary human macrophages stimulated by C5a were similarly inhibited. C5a‐evoked migration in RAW264.7 cells was significantly suppressed by wortmannin (phosphatidylinositol 3‐kinase (PI3K) inhibitor), PD98059 (MEK1/2 inhibitor) and SB203580 (p38 mitogen‐activated protein kinase (MAPK) inhibitor), but not by SP600125 (c‐Jun N‐terminal kinase (JNK) inhibitor), suggesting that activation of PI3K, ERK1/2 and p38 MAPK signal pathways was involved in responses to C5a. Western blotting revealed that cryptotanshinone significantly inhibited PI3K‐p110γ membrane translocation and phosphorylation of Akt (PI3K downstream effector protein) and ERK1/2 induced by C5a. However, neither p38 MAPK nor JNK phosphorylation was affected by cryptotanshinone. Wortmannin significantly attenuated C5a‐induced PI3K‐p110γ translocation, Akt and ERK1/2 phosphorylation. PD98059 suppressed ERK1/2 phosphorylation but failed to modify PI3K‐p110γ translocation by C5a stimulation. Furthermore, MIP‐1α‐induced cell migration and PI3K‐p110γ translocation were also inhibited by cryptotanshinone in a concentration‐dependent manner.

Conclusions and implications:

Inhibition of macrophage migration by cryptotanshinone involved inhibition of PI3K activation with consequent reduction of phosphorylation of Akt and ERK1/2.

British Journal of Pharmacology(2007)151, 638–646; doi:10.1038/sj.bjp.0707271
Weak ferromagnetism in single crystalline YbB6−δ
Authors: Kim J. Y. , Sung N. H. , Cho B. K.
Published: April 2007

We present a study of magnetization and transport properties of single crystals of YbB6 and YbB6±δ (δ=0.3 as a nominal value). The YbB6−δ crystal revealed a weak ferromagnetism, manifested by hysteresis loop in M(H) at room temperature with a saturation magnetic moment of 1.5×10−4μB∕f.u. and the ferromagnetic transition temperature higher than T=300K, whereas YbB6 and YbB6+δ crystals revealed diamagnetism and paramagnetism, respectively. It was found that the bulk magnetic property of YbB6±δ crystals is intrinsically diamagnetic and that the magnetism, ferromagnetism, or paramagnetism is a surface effect. Based on x-ray photoelectron spectroscopy and electron probe microanalyzer measurements, we believed that the extraneous magnetic impurities, such as Fe and Ni, are not the origin of the ferromagnetism or paramagnetism. While we observed from electrical resistivity and Hall resistivity that the off stoichiometry in YbB6±δ causes carrier doping effect, it is not clear at present what surface state creates the magnetic signals.
Material design of hole transport materials capable of thick-film formation in organic light emitting diodes
Authors: Aonuma Masaki , Oyamada Takahito , Sasabe Hiroyuki , Miki Tetsuzou , Adachi Chihaya
Published: April 2007

In this study, the authors show an empirical guideline for designing hole transport materials (HTMs) that suppress rises in driving voltage even with a few hundred nanometer thick film in the organic light emitting diodes (OLEDs). In a device structure of indium tin oxide (110nm)/hole transport layer (HTL) (Xnm)∕4,4′-N,N′-bis[N-(1-naphthyl)-N-phenyl-amino]biphenyl (10nm)/tris-(8-hydroxyquinoline)aluminum (Alq3) (50nm)∕MgAg (100nm)∕Ag (10nm), the authors compared electroluminescence characteristics of the OLEDs having a thin-film HTL (X=50nm) and a thick-film HTL (X=300nm) using 13 kinds of HTMs. They observed a closed correlation between suppression of the driving voltage and the HTMs’ thermal characteristics. Highly thermally stable HTMs resulted in a small increase in the driving voltage.
Nanoscale surface plasmon based resonator using rectangular geometry
Authors: Hosseini Amir , Massoud Yehia
Published: April 2007

The authors present an optical range resonator based on single mode metal-insulator-metal plasmonic gap waveguides. Complete transmission at 90° bends would enable the design of rectangular structures with cross-section area less than 500nm2, which consequently leads to easing the fabrication process. The resonator exhibits a free spectral range of 270nm. We show that a small bridge between the resonator and the input waveguide can be used to tune the resonance frequency. In addition, ultracompact add/drop directional couplers are realizable using the presented ring resonator structure.
Effect of residual solvent and thermal annealing on a light-emitting polymer-based electrochemical cell
Authors: Zhao Wei , White J. M.
Published: April 2007

The effect of residual solvents and thermal annealing on light-emitting electrochemical cells constructed using poly[2-methoxy-5-(2′-ethyl-hexyloxy)-1,4-phenylene vinylene] and poly(ethylene oxide) (PEO) doped with lithium trifluoromethanesulfonate (Li triflate) was investigated. The turn-on voltage dropped when the films were annealed in dry and vacuum atmospheres. This is attributed to the removal of residual solvents that are detected by mass spectrometry in ultrahigh vacuum. The results are interpreted in terms of a model in which ionized Li triflate has higher ionic conductivity in the presence of dry PEO than when solvated by water or cyclohexanone within a PEO matrix.
Investigation of space charge at pentacene/metal interfaces by a near-field scanning microwave microprobe
Authors: Babajanyan Arsen , Lee Kiejin , Lim Eunju , Manaka Takaaki , Iwamoto Mitsumasa , Friedman Barry
Published: April 2007

Space charge properties at the interface of pentacene thin films on gold (Au) and aluminum (Al) surfaces were investigated by using a near-field scanning microwave microprobe. The space charge was observed by measuring the microwave reflection coefficient S11 and compared with the result of a Kelvin-probe method. The obtained ΔS11 of the pentacene thin films on Al increased as the pentacene film thickness increased due to the accumulation of negative space charges. Using the pentacene field effect transistor with a Au source, hole injection from the Au electrode into pentacene with varying drain source biasing was imaged by near-field scanning microwave microprobe.
Relationships between seasonal patterns of live fuel moisture and meteorological drought indices for Mediterranean shrubland species
Authors: Pellizzaro G. , Cesaraccio C. , Duce P. , Ventura A. , Zara P.
Published: April 2007

Measurements of seasonal patterns of live fuel moisture content and ignitability (in terms of time to ignition) of four Mediterranean shrub species were performed in North Western Sardinia (Italy). Relationships between the two variables were evaluated. Relationships between live fuel moisture content and environmental conditions (i.e. rainfall, air temperature and soil moisture) were analysed. Two groups of species were identified in relation to the different response of live fuel moisture content to seasonal meteorological conditions. Seasonal patterns of live fuel moisture content were also compared with five meteorological drought indices: Duff Moisture Code and Drought Code of the Canadian Forest Fire Weather Index System, Keetch–Byram Drought Index, Canopy Drought Stress Index and Cumulative Water Balance Index. In addition, the capability of the meteorological drought indices to describe moisture variation for each species was evaluated. Although the Drought Code was formulated to describe changes in the moisture content of dead fuel, it was shown to have a good potential for modelling live fuel moisture variation of a group of shrubland species that are sensitive to meteorological conditions, with a clear and large decrease of moisture content during the drought season.
Local-scale modelling system to simulate smoke dispersion
Authors: Valente Joana , Miranda Ana I. , Lopes António G. , Borrego Carlos , Viegas Domingos X. , Lopes Myriam
Published: April 2007

The main purpose of this paper is to present a fire behaviour system, developed to estimate fire progression, smoke dispersion and visibility impairment, at a local scale, and to evaluate its performance by comparing results with measurements from the Gestosa 2004 experimental field fires. The system is an improvement of two already available numerical tools, DISPERFIRE (Miranda et al. 1994) and FireStation (Lopes et al. 2002), which were integrated. FireStation is a software system aimed at the simulation of fire spread over complex topography. DISPERFIRE is a real-time system developed to simulate the dispersion in the atmosphere of the pollutants emitted during a forest fire. In addition, a model for the estimation of visibility impairment, based on the relationship between air pollutants concentration and visibility, was included in DISPERFIRE. The whole system was developed using a graphical interface, previously created for FireStation, which provides user-friendliness and easily readable output to facilitate its application under operational conditions. The system was applied to an experimental field fire and the main results were compared with experimental air pollutant concentration measured values. The performance of the model in predicting pollutant concentrations was good, particularly for NO2 and PM10.
Multiple Forms of Cardiac Myosin-binding Protein C Exist and Can Regulate Thick Filament Stability
Authors: Kulikovskaya Irina , McClellan George B. , Levine Rhea , Winegrad Saul
Published: April 2007

Although absence or abnormality of cardiac myosin binding protein C (cMyBP-C) produces serious structural and functional abnormalities of the heart, function of the protein itself is not clearly understood, and the cause of the abnormalities, unidentified. Here we report that a major function of cMyBP-C may be regulating the stability of the myosin-containing contractile filaments through phosphorylation of cMyBP-C. Antibodies were raised against three different regions of cMyBP-C to detect changes in structure within the molecule, and loss of myosin heavy chain was used to monitor degradation of the thick filament. Results from Western blotting and polyacrylamide gel electrophoresis indicate that cMyBP-C can exist in two different forms that produce, respectively, stable and unstable thick filaments. The stable form has well-ordered myosin heads and requires phosphorylation of the cMyBP-C. The unstable form has disordered myosin heads. In tissue with intact cardiac cells, the unstable unphosphorylated cMyBP-C is more easily proteolyzed, causing thick filaments first to release cMyBP-C and/or its proteolytic peptides and then myosin. Filaments deficient in cMyBP-C are fragmented by shear force well tolerated by the stable form. We hypothesize that modulation of filament stability can be coupled at the molecular level with the strength of contraction by the sensitivity of each to the concentration of calcium ions.
A Direct Demonstration of Closed-State Inactivation of K+ Channels at Low pH
Authors: Claydon Thomas W. , Vaid Moni , Rezazadeh Saman , Kwan Daniel C.H. , Kehl Steven J. , Fedida David
Published: April 2007

Lowering external pH reduces peak current and enhances current decay in Kv and Shaker-IR channels. Using voltage-clamp fluorimetry we directly determined the fate of Shaker-IR channels at low pH by measuring fluorescence emission from tetramethylrhodamine-5-maleimide attached to substituted cysteine residues in the voltage sensor domain (M356C to R362C) or S5-P linker (S424C). One aspect of the distal S3-S4 linker α-helix (A359C and R362C) reported a pH-induced acceleration of the slow phase of fluorescence quenching that represents P/C-type inactivation, but neither site reported a change in the total charge movement at low pH. Shaker S424C fluorescence demonstrated slow unquenching that also reflects channel inactivation and this too was accelerated at low pH. In addition, however, acidic pH caused a reversible loss of the fluorescence signal (pKa = 5.1) that paralleled the reduction of peak current amplitude (pKa = 5.2). Protons decreased single channel open probability, suggesting that the loss of fluorescence at low pH reflects a decreased channel availability that is responsible for the reduced macroscopic conductance. Inhibition of inactivation in Shaker S424C (by raising external K+ or the mutation T449V) prevented fluorescence loss at low pH, and the fluorescence report from closed Shaker ILT S424C channels implied that protons stabilized a W434F-like inactivated state. Furthermore, acidic pH changed the fluorescence amplitude (pKa = 5.9) in channels held continuously at −80 mV. This suggests that low pH stabilizes closed-inactivated states. Thus, fluorescence experiments suggest the major mechanism of pH-induced peak current reduction is inactivation of channels from closed states from which they can activate, but not open; this occurs in addition to acceleration of P/C-type inactivation from the open state.