bluuebunny/crossref_metadata_2025 huggingface dataset:
BARRING RECOVERY FOR DIMINUTION IN VALUE OF SHARES ON THE REFLECTIVE LOSS PRINCIPLE
Authors: Lee Suet Lin Joyce
Published: November 2007

The question of whether a shareholder may bring a personal action to recover diminution in value of his shares as a result of a wrong committed by the defendant against the company appears to be settled by the House of Lords in Johnson v. Gore Wood & Co. (to be referred to as the Johnson case). The facts may be stated briefly. Gore Wood, a firm of solicitors, had acted for Johnson's company, in which he owned almost entirely all the shares. The solicitors were alleged to have acted negligently when they failed to exercise an option to purchase a piece of land for Johnson's company. The solicitors then settled a suit brought by the company. After the settlement, Johnson sued the solicitors, arguing that they also owed a duty to him personally. As some of the losses claimed by Johnson were also losses which the company suffered and which had been settled, the solicitors applied to strike out those claims on the ground that they were “reflective losses”. The House of Lords struck out those claims which were reflective losses, namely, claims for diminution in value of his shares and reduction in dividend stream, but allowed other claims to go to trial. The concern of this article is with a shareholder's personal claim for diminution in value of shares.
PUBLIC, PRIVATE AND THE HUMAN RIGHTS ACT 1998: AN IDEOLOGICAL DIVIDE
Authors: Palmer Stephanie
Published: November 2007

The House of Lords decision in YL v. Birmingham City Council considers the issue of what
is a public authority under the Human Rights Act 1998. The question is a
critical one as the Convention rights, contained in the Human Rights Act, are
directly enforceable only against public authorities. The issue of whether a
body is a public authority has proved highly controversial. The hiving-off of
many traditional governmental functions through policies such as privatisation,
outsourcing and projects under the Private Finance Initiative (PFI) has led to
a blurring of the traditionally understood public-private distinction. The
changed nature in the way that public services are delivered has led to sharply
divergent views among the judiciary about which functions are those of a public
nature for the purposes of the Human Rights Act. This is evident in the
YL judgment itself: a split decision,
with two dissenting judgements. The division in the House reflects different
understandings of the operation of the Human Rights Act, the public-private
distinction and, perhaps more fundamentally, competing ideological stances.
INJUNCTIONS ENJOINING NON-PARTIES: DISTINCTION WITHOUT DIFFERENCE?
Authors: Seymour Jillaine
Published: November 2007

Ordinarily, claimants seeking injunctive relief will be able to identify by name the individuals likely to interfere with their rights. However, claimants increasingly anticipate that they will be harassed, their property damaged or confidential information revealed by persons difficult or impossible to identify. In M Michaels (Furriers) Ltd v. Askew the claimant's commercial premises were under sustained attack from animal rights activists. The claimant “had difficulty in identifying all those responsible for these damaging actions” and addressed this difficulty by bringing a representative action against, among others, the national organiser and local contact of Animal Aid as the representatives of all members of that organisation. The Court of Appeal upheld the interim injunction granted against these representative defendants restraining them, and therefore all members of Animal Aid, from, inter alia, damaging, injuring or trespassing on the claimant's premises. In Hampshire Waste Services Ltd v. Persons Intending to Trespass and/or Trespassing Upon Incinerator Sites the four owners of a number of incinerator sites faced a similar problem. Incinerators had been targeted for protest, sometimes on a predetermined and advertised day described as a “Global Day of Action Against Incinerators”. Evidence suggested that such a protest was planned but the claimants were “unable to name any of the protesters who might be involved” and their claim was brought against “Persons intending to trespass and/or trespassing upon incinerator sites” at six locations. Morritt V.C. made an order binding “persons entering or remaining without the consent of the claimants ... on any of the incinerator sites ... in connection with the ‘Global Day of Action Against Incinerators’ (or similarly described event) on or around 14 July 2003”.
The Sensitivity of the Dinoflagellate Crypthecodinium cohnii to Transient Hydrodynamic Forces and Cell‐Bubble Interactions
Authors: Hu Weiwei , Gladue Ray , Hansen Jon , Wojnar Crystal , Chalmers Jeffrey J.
Published: November 2007

The increased interest in the benefits of omega‐3 fatty acids for human health has resulted in the commercial development of the dinoflagellate Crypthecodinium cohnii for production of docosahexaenoic acid (DHA). The growing market demand for DHA requires highly efficient, very large scale cultures of DHA. While the effects of hydrodynamic forces on dinoflagellates have been investigated for several decades, the majority of the work focused on the negative effects of oceanic turbulence on the population growth of environmentally important dinoflagellates. In contrast, significantly less is known on the effect of hydrodynamic forces encountered by algae in bioprocesses. Unlike other studies conducted on algae, this study employed a microfluidic, flow contraction device to evaluate the effect of transient hydrodynamic forces on C. cohnii cells. It was found that C. cohnii cells can sustain the energy dissipation rate of 5.8 × 107 W/m3 without lysis. However, an obvious sublethal effect, the loss of flagella, was observed at a lower level of 1.6 × 107 W/m3. Finally the cell‐bubble interaction and the effect of bubble rupture were also explored to simulate the conditions of sparged bioreactors.
Veränderte Schmeckwahrnehmung bei Patientinnen mit Essstörungen
Authors: Wöckel Lars , Hummel Thomas , Daniel Zepf Florian , Jacob Alice , Poustka Fritz
Published: November 2007

Zusammenfassung: Fragestellung: Geschmack ist ein vererbtes Merkmal und beeinflusst Essgewohnheiten und Diätverhalten. Die Papillen der Zunge repräsentieren das erste Segment des gustatorischen Systems um die Schmeckinformationen zu erfassen. Ziel dieser Studie war es, die Anzahl der fungiformen Papillen (fPap) in Verbindung mit der 6-n-Propylthiouracil (PROP)-Sensitivität und dem Body Mass Index (BMI) bei Patientinnen mit Essstörungen zu bestimmen. Methodik: 18 Patientinnen mit Essstörungen (Anorexia oder Bulimia nervosa, Altersbereich 14-20 Jahre) und 15 altersentsprechende weibliche Probandinnen wurden in die Studie eingeschlossen. Die Anzahl der fPap wurde gemessen. Der Bittergeschmack wurde mit PROP untersucht. Verschiedene BMIs (z.B. minimaler BMI, maximaler BMI) wurden berechnet. Ergebnisse: Anorektische Nicht-Schmecker (PROP negativ) hatten im Vergleich zu den Nicht-Schmeckern der Kontrollgruppe und der Bulimiegruppe eine signifikant verminderte Anzahl an fPap. Die Anzahl von fPap unterschied sich nicht signifikant zwischen Schmeckern und Nicht-Schmeckern innerhalb der Kontrollgruppe und den Essstörungsgruppen. Es zeigte sich ein Trend für einen höheren BMI bei den bulimischen und den gesunden Nicht-Schmeckern. Schlussfolgerungen: Eine verminderte Geschmackspapillendichte bei anorektischen Patientinnen wird von einer verminderten PROP-Sensitivität begleitet. Der Zusammenhang zwischen PROP-Sensitivität und Essstörungen ist bisher nicht bekannt. Wir vermuten einen Einfluss auf die Schmeckwahrnehmung und die Pathophysiologie des Essverhaltens.
Bewegungsdiagnostik und -therapie in der Kinder- und Jugendpsychiatrie - eine Standortbestimmung
Authors: Welsche Mone , Stobbe Cordula , Hölter Gerd , Romer Georg
Published: November 2007

Zusammenfassung: Fragestellung: Der vorliegende Beitrag gibt einen umfassenden Überblick über den Bereich der Bewegungsdiagnostik und -therapie an deutschen Klinken für Kinder- und Jugendpsychiatrie. Methodik: Dabei können auf Grundlage von zwei Fragebogenerhebungen Aussagen über die derzeitige Situation der klinisch tätigen Bewegungsdiagnostiker/innen sowie -therapeut/innen gemacht werden. Ergebnisse: Hierzu werden Angaben über die in diesem Bereich tätigen Berufsgruppen, eingesetzte diagnostische Verfahren, der Therapie zugrunde liegende Konzepte und Ansätze, sowie verfolgte Ziele dargestellt. Insgesamt wird die große Vielfalt des Fachgebietes sowohl bezüglich der tätigen Berufsgruppen als auch bezüglich der verwendeten Diagnostikverfahren und therapeutischen Konzepte deutlich. Schlussfolgerung: Ausgehend von dieser Vielfalt wird die Notwendigkeit der Schärfung des Profils des Fachgebietes diskutiert sowie ein Ausblick über die Etablierung von bewegungstherapeutischen Verfahren im kinder- und jugendpsychiatrischen Kontext gegeben.
Equator‐S observations of drift mirror mode waves in the dawnside magnetosphere
Authors: Rae I. Jonathan , Mann Ian R. , Watt Clare E. J. , Kistler Lynn M. , Baumjohann Wolfgang
Published: November 2007

The mirror mode is a plasma instability that is typically excited in high‐beta plasmas where there is significant pressure anisotropy and is most commonly observed in the magnetosheath. However, it is possible under sufficiently anisotropic conditions to generate the mirror instability inside the magnetosphere, though as yet there are few examples. We present an extended interval of ∼7 hours of mirror mode activity on 19 March 1998 when the Equator‐S spacecraft was traversing the dawnside magnetosphere above the equatorial plane at radial distances of up to L ∼ 11 and encountered quasi‐monochromatic ∼2‐min oscillations in magnetic field and ion number density, temperature, and velocity. The magnetic field strength and number densities were in antiphase, and the plasma and magnetic field pressure perturbations were also in antiphase while the observed total pressure remained constant. This is consistent with excitation via a mirror instability. We are able to discern that the mirror activity must be confined to approximately within ±20° of the equatorial plane through a conjunction with the Geotail spacecraft. We find that the condition for mirror mode waves to grow is strongly met throughout the interval (Hasegawa, 1969). We believe that this is an excellent high temporal resolution example of the mirror instability exciting ULF waves inside the Earth's magnetosphere. Given the coexistence of toroidal oscillations at almost the same frequency, we suggest coupling between the mirror mode and local standing Alfvén waves. Our observations hence add to the understanding of how energy can be transferred from hot plasma into ULF waves in the magnetosphere before being dissipated in the ionosphere.
Inventory of African desert dust events over the southwestern Iberian Peninsula in 2000–2005 with an AERONET Cimel Sun photometer
Authors: Toledano C. , Cachorro V. E. , de Frutos A. M. , Sorribas M. , Prats N. , de la Morena B. A.
Published: November 2007

Routine aerosol measurements are carried out at El Arenosillo station (37.1°N, 6.7°W), in Huelva (Spain), since February 2000 with a Cimel Sun photometer included in the AERONET network. This station, located in the coast of the southwestern Iberian Peninsula, is an appropriate site for the detection and characterization of desert dust aerosols arriving from North Africa. The aerosol database allows us to make an inventory of desert dust events over 6 years corresponding to the period 2000–2005. The inventory is based on threshold values for the aerosol optical depth (AOD) and Ångström exponent, the analysis of the size distributions, a manual inspection, and the use of air mass back trajectories as complementary information. This inventory shows the presence of desert aerosols 65 d yr−1 (18% of days), although there are significant differences among years. Desert dust events have a mean duration of 4 days, with mean AOD (440 nm) of 0.31 and mean Ångström exponent of 0.66. The desert dust episodes are more frequent in February, March, and the summer months. During autumn, winter, and April the episodes are less frequent. This seasonal pattern of the desert events influences the AOD at El Arenosillo, which presents an analogous seasonal pattern. Because of the desert events, AOD levels increase 28% at 440 nm and 48% at 870 nm. Desert dust intrusions have been also catalogued according to four basic meteorological scenarios. The analysis of the desert inventory has made it possible to establish an automatic method for the detection of the desert dust intrusions over the Iberian Peninsula with Sun photometer data. Finally, a classification of air masses (based on back trajectories) has been compared with the occurrence of desert dust intrusions.
Arctic tundra shrub invasion and soot deposition: Consequences for spring snowmelt and near‐surface air temperatures
Authors: Strack John E. , Pielke Roger A. , Liston Glen E.
Published: November 2007

Invasive shrubs and soot pollution both have the potential to alter the surface energy balance and timing of snow melt in the Arctic. Shrubs reduce the amount of snow lost to sublimation on the tundra during the winter leading to a deeper end‐of‐winter snowpack. The shrubs also enhance the absorption of energy by the snowpack during the melt season by converting incoming solar radiation to longwave radiation and sensible heat. Soot deposition lowers the albedo of the snow, allowing it to more effectively absorb incoming solar radiation and thus melt faster. This study uses the Colorado State University Regional Atmospheric Modeling System version 4.4 (CSU‐RAMS 4.4), equipped with an enhanced snow model, to investigate the effects of shrub encroachment and soot deposition on the atmosphere and snowpack in the Kuparuk Basin of Alaska during the May–June melt period. The results of the simulations suggest that a complete invasion of the tundra by shrubs leads to a 2.2°C warming of 3 m air temperatures and a 108 m increase in boundary layer depth during the melt period. The snow‐free date also occurred 11 d earlier despite having a larger initial snowpack. The results also show that a decrease in the snow albedo of 0.1, owing to soot pollution, caused the snow‐free date to occur 5 d earlier. The soot pollution caused a 1.0°C warming of 3 m air temperatures and a 25 m average deepening of the boundary layer.
Multistep ahead streamflow forecasting: Role of calibration data in conceptual and neural network modeling
Authors: Toth Elena , Brath Armando
Published: November 2007

When choosing the rainfall‐runoff modeling approach to be integrated in a river flow forecasting system, two crucial issues are the minimum data requirement for calibration purposes and the reliability of the predictions over different time horizons (lead‐times). The paper presents an investigation of the real‐time forecasting ability of a conceptual and a neural network model, comparing the performances obtainable for increasing lead‐times and analyzing the influence of the amount of the calibration data over two real‐data case studies. Neural networks proved to be an excellent tool for the real‐time rainfall‐runoff simulation of continuous periods (including low, average and peak flows), provided that an extensive set of hydro‐meteorological data is available for calibration purposes. On the other hand, the comparison highlights that a conceptual formulation may allow a significant forecasting improvement in comparison with the data‐driven approach when focusing on the prediction of flood events and especially in case of a limited availability of calibration data.
Flux and age of dissolved organic carbon exported to the Arctic Ocean: A carbon isotopic study of the five largest arctic rivers
Authors: Raymond Peter A. , McClelland J. W. , Holmes R. M. , Zhulidov A. V. , Mull K. , Peterson B. J. , Striegl R. G. , Aiken G. R. , Gurtovaya T. Y.
Published: November 2007

The export and Δ14C‐age of dissolved organic carbon (DOC) was determined for the Yenisey, Lena, Ob', Mackenzie, and Yukon rivers for 2004–2005. Concentrations of DOC elevate significantly with increasing discharge in these rivers, causing approximately 60% of the annual export to occur during a 2‐month period following spring ice breakup. We present a total annual flux from the five rivers of ∼16 teragrams (Tg), and conservatively estimate that the total input of DOC to the Arctic Ocean is 25–36 Tg, which is ∼5–20% greater than previous fluxes. These fluxes are also ∼2.5× greater than temperate rivers with similar watershed sizes and water discharge. Δ14C‐DOC shows a clear relationship with hydrology. A small pool of DOC slightly depleted in Δ14C is exported with base flow. The large pool exported with spring thaw is enriched in Δ14C with respect to current‐day atmospheric Δ14C‐CO2 values. A simple model predicts that ∼50% of DOC exported during the arctic spring thaw is 1–5 years old, ∼25% is 6–10 years in age, and 15% is 11–20 years old. The dominant spring melt period, a historically undersampled period, exports a large amount of young and presumably semilabile DOC to the Arctic Ocean.
Charged particle environment of Titan during the T9 flyby
Authors: Szego K. , Bebesi Z. , Bertucci C. , Coates A. J. , Crary F. , Erdos G. , Hartle R. , Sittler E. C. , Young D. T.
Published: November 2007

The ion measurements of the Cassini Plasma Spectrometer are presented which were acquired on 26 December 2005, during the T9 flyby at Titan. The plasma flow and magnetic field directions in the distant plasma environment of the moon were distinctly different from the other flybys. The near‐Titan environment, dominated by ions of Titan origin, had a split signature, each with different ion composition; the first region was dominated by dense, slow, and cold ions in the 16–19 and 28–40 amu mass range, the second region contained only ions with mass 1 and 2, much less dense and less slow. Magnetospheric ions penetrate marginally into region 1, whereas the region‐2 ion population is mixed. A detailed analysis has led us to conclude that the first event was due to the crossing of the mantle of Titan, whereas the second one very likely was a wake crossing. The split indicates the non‐convexity of the ion‐dominated volume around Titan. Both ion distributions are analysed in detail.
Structure of Titan's mid‐range magnetic tail: Cassini magnetometer observations during the T9 flyby
Authors: Bertucci C. , Neubauer F. M. , Szego K. , Wahlund J.‐E. , Coates A. J. , Dougherty M. K. , Young D. T. , Kurth W. S.
Published: November 2007

We analyze the magnetic structure of Titan's mid‐range magnetic tail (5–6 Titan radii downstream from the moon) during Cassini's T9 flyby. Cassini magnetometer (MAG) measurements reveal a well‐defined, induced magnetic tail consisting of two lobes and a distinct central current sheet. MAG observations also indicate that Saturn's background magnetic field is close to the moon's orbital plane and that the magnetospheric flow has a significant component in the Saturn‐Titan direction. The analysis of MAG data in a coordinate system based on the orientation of the background magnetic field and an estimation of the incoming flow direction suggests that Titan's magnetic tail is extremely asymmetric. An important source of these asymmetries is the connection of the inbound tail lobe and the outbound tail lobe to the dayside and nightside hemispheres of Titan, respectively. Another source could be the perturbations generated by changes in the upstream conditions.
Atmospheric transformation of enols: A potential secondary source of carboxylic acids in the urban troposphere
Authors: Archibald Alex T. , McGillen Max R. , Taatjes Craig A. , Percival Carl J. , Shallcross Dudley E.
Published: November 2007

Following the recent discovery that enols are important intermediates in combustion chemistry, the possible impact of these species on atmospheric chemistry is investigated. A novel mechanism is proposed by which the reactions of enols contribute significantly towards atmospheric carboxylic acid concentrations in the gas‐phase. Inclusion of ethenol in the Common Representative Intermediates CRI mechanism was found to increase predicted secondary production of formic acid considerably (∼40 pptv in the first 6 hours in a base case scenario, with typical increases of [HCOOH] ranging from 20–60 pptv over a period of 96 hours) whereas its effect on other important trace species (i.e. O3, NOx, HOx and HCHO) was negligible. Carboxylic acid concentrations are at present underestimated by major atmospheric chemical models, and these results indicate that the atmospheric transformation of enols may be an important missing secondary source term for carboxylic acids in the urban troposphere.
Variability in HDO/H2O abundance ratios in the tropical tropopause layer
Authors: Nassar Ray , Bernath Peter F. , Boone Chris D. , Gettelman Andrew , McLeod Sean D. , Rinsland Curtis P.
Published: November 2007

The dehydration of air in the tropical tropopause layer (TTL) and mechanisms for the entry of water vapor into the stratosphere are investigated by an analysis of ACE‐FTS profiles of temperature, water vapor, and the ratio [HDO]/[H2O] expressed in δD notation. Month‐to‐month comparisons indicate greater seasonal variability than interannual variability between 25°S–25°N, thus comparisons are made between February, April, August, and October averages for the years 2004 and 2005 combined. The data indicate a pattern of seasonal variability which is clearer in the Northern Hemisphere tropics and a relationship between minimum temperature, minimum water vapor, and maximum HDO depletion, which exists beyond the estimated uncertainty in these values. The range of values observed for HDO depletion and comparisons to modeled Rayleigh distillation curves indicate an important contribution from convection in addition to gradual dehydration. Multiple factors including the shape of the δD profiles suggest that a likely mechanism for the convective influence is the lofting of ice particles in the tropical troposphere.
Retrieval of effective radius and liquid water path from ground‐based instruments: A case study at Barrow, Alaska
Authors: Schofield Robyn , Daniel John S. , Portmann Robert W. , Miller H. LeRoy , Solomon Susan , Eubank Charles S. , Melamed Megan L. , Langford Andrew O. , Shupe Matthew D. , Turner David D.
Published: November 2007

Two methods for retrieving cloud droplet effective radius re from ground‐based near‐infrared spectral measurements of path‐integrated liquid water paths (PLWPs) are described. In one method the PLWP is compared with column measurements of liquid water path (LWP) from a dual channel microwave radiometer (MWR) to estimate the cloud path enhancement, which is then used to derive the cloud droplet effective radius. In the second method, PLWP is combined with absolutely calibrated zenith radiances at 500 nm to retrieve re and LWP simultaneously. Both techniques are used in a case study of marine stratocumulus at the Barrow, Alaska (71.32°N, 156.62°W) Atmospheric Radiation Measurement Program (ARM) site on 17 September 2004. The first method performed best for moderately thick clouds (LWP ≥ 100 g m−2), but the accuracy is limited by uncertainties in the MWR LWP on which it relies. The second method performed well over a wider range of values with 1σ retrieval errors of <4 g m−2 (∼4%) and ∼3 μm (∼7%) for 15 ≤ LWP ≤ 170 g m−2. The LWPs retrieved using the radiance‐PLWP method were highly correlated (r2 = 0.96) with LWPs from the MWR (with a bias subtracted) derived using the ARM statistical method. A limited comparison (LWP < 100 g m−2) to millimeter wave cloud radar showed that values of re retrieved using the radiance‐PLWP method were consistently higher (by ∼3 μm) than the LWC‐weighted mean re from the radar. Additional field studies are needed to resolve this discrepancy, although this first comparison is promising.
Heat capacity, time constant, and sensitivity of Earth's climate system
Authors: Schwartz Stephen E.
Published: November 2007

The equilibrium sensitivity of Earth's climate is determined as the quotient of the relaxation time constant of the system and the pertinent global heat capacity. The heat capacity of the global ocean, obtained from regression of ocean heat content versus global mean surface temperature, GMST, is 14 ± 6 W a m−2K−1, equivalent to 110 m of ocean water; other sinks raise the effective planetary heat capacity to 17 ± 7 W a m−2K−1(all uncertainties are 1‐sigma estimates). The time constant pertinent to changes in GMST is determined from autocorrelation of that quantity over 1880–2004 to be 5 ± 1 a. The resultant equilibrium climate sensitivity, 0.30 ± 0.14 K/(W m−2), corresponds to an equilibrium temperature increase for doubled CO2of 1.1 ± 0.5 K. The short time constant implies that GMST is in near equilibrium with applied forcings and hence that net climate forcing over the twentieth century can be obtained from the observed temperature increase over this period, 0.57 ± 0.08 K, as 1.9 ± 0.9 W m−2. For this forcing considered the sum of radiative forcing by incremental greenhouse gases, 2.2 ± 0.3 W m−2, and other forcings, other forcing agents, mainly incremental tropospheric aerosols, are inferred to have exerted only a slight forcing over the twentieth century of −0.3 ± 1.0 W m−2.
Nighttime nitrate radical chemistry at Appledore Island, Maine during the 2004 International Consortium for Atmospheric Research on Transport and Transformation
Authors: Ambrose J. L. , Mao H. , Mayne H. R. , Stutz J. , Talbot R. , Sive B. C.
Published: November 2007

Trace gases including nitrogen dioxide (NO2), nitrate radical (NO3), ozone (O3), and a suite of volatile organic compounds (VOCs) were measured within the New England coastal marine boundary layer on Appledore Island (AI), Maine, USA as part of the International Consortium for Atmospheric Research on Transport and Transformation (ICARTT) field campaign. These measurements, together with local meteorological records and published kinetic data were used to investigate nighttime NO3 chemistry at AI during the period of 8–28 July 2004. Among the VOCs, isoprene, monoterpenes and dimethylsulfide (DMS) were the dominant NO3 reactants; on average, DMS accounted for 51 ± 34% of the total reactivity. For three case studies, NO3 mixing ratios were calculated from measured parameters with resultant uncertainties of ≤30%. Discrepancies with measured NO3 appeared to result primarily from input parameter variability and exclusion of heterogeneous dinitrogen pentoxide (N2O5) chemistry. We indirectly determined that nighttime NO3 and NOx (=NO + NO2) removal via N2O5 chemistry (gas‐phase + heterogeneous) was on average 51–54% and 63–66% of the total respectively. Our analysis suggested that the minimum average NO3 and NOx removal via heterogeneous N2O5 chemistry was ∼10% of the total. Reducing gas‐phase N2O5 reactivity in accord with Brown et al. (2006a) increased the importance of heterogeneous N2O5 chemistry substantially. It is plausible that the latter pathway was often comparable to gas‐phase removal of NO3 and NOx. Overall, 24 h‐averaged NOx removal was ∼11 ppbv, with nighttime chemical pathways contributing ∼50%.
Controls on major solutes within the drainage network of a rapidly weathering tropical watershed
Authors: Bhatt Maya P. , McDowell William H.
Published: November 2007

Surface water chemistry in the main stem and source points of the Rio Icacos basin (Luquillo Experimental Forest, Puerto Rico) was studied to investigate the factors regulating spatial variability in major solutes in a rapidly weathering landscape. We sampled along the main stem as well as at small source points at high elevation where fresh bedrock is frequently exposed, and at low elevation in the floodplain/colluvial plain of the main stem. Concentrations of silicon, alkalinity, and the sum of base cations were lower at the source points than in the main stem, and were lowest in low‐elevation source points. Calcium and sodium were the dominant cations at all sampling points after sea‐salt correction, reflecting the weathering of plagioclase feldspar throughout the basin. The partial pressure of carbon dioxide (pCO2) tended to be higher, and HCO3− concentrations were lower, in the low‐elevation source points than at other positions in the landscape. When coupled with the relatively low concentrations of Si and base cations, this suggests that the availability of primary reactive minerals, rather than carbonic acid concentrations, limits weathering in these low‐elevation sources. Mechanical denudation appears to enhance chemical weathering rates not only by refreshing reactive mineral surfaces but also by contributing carbon dioxide from the decomposition of organic‐rich material in landslides, which occur frequently. The spatial variability of major solutes appears to depend primarily on the availability of fresh primary reactive minerals, carbon dioxide concentrations, and hydrolysis conditions.
Internalization: what does it tell us about pharmacokinetic and pharmacodynamic properties of an antagonist?
Authors: Mueller A
Published: November 2007

Chemokine receptors play an important role in trafficking leukocytes within the body, a process that depends on expression of the receptors on the cell surface. Expression levels are regulated by the rate of internalizing receptor compared to the rate of recycling/recovering receptor. Internalization is commonly induced by binding of agonists to their receptors that in turn use clathrin‐coated pits or caveolae to internalize. Joplin and colleagues describe a novel usage of internalization assays to determine pharmacokinetic/pharmacodynamic relationships of an antagonist on CXCR3 in a murine system. Intriguingly their results show that internalization assays give robust data about the pharmacokinetics/pharmacodynamics of different agonists and antagonists in an in vivo model. This kind of assay will allow investigations of the pharmacological properties of agonists and antagonists in a completely different setting and also give new insight into the regulation of cell surface expression of chemokine receptors and other G protein‐coupled receptors, which can lead to potential novel therapeutic targets.

British Journal of Pharmacology (2007) 152, 1145–1146; doi:10.1038/sj.bjp.0707521; published online 5 November 2007
Structural and mechanistic studies on the peroxisomal oxygenase phytanoyl-CoA 2-hydroxylase (PhyH)
Authors: Schofield C.J. , McDonough M.A.
Published: November 2007

Phytanic acid (PA) is an epimeric metabolite of the isoprenoid side chain of chlorophyll. Owing to the presence of its epimeric β-methyl group, PA cannot be metabolized by β-oxidation. Instead, it is metabolized in peroxisomes via α-oxidation to give pristanic acid, which is then oxidized by β-oxidation. PhyH (phytanoyl-CoA 2-hydroxylase, also known as PAHX), an Fe(II) and 2OG (2-oxoglutarate) oxygenase, catalyses hydroxylation of phytanoyl-CoA. Mutations of PhyH ablate its role in α-oxidation, resulting in PA accumulation and ARD (adult Refsum's disease). The structure and function of PhyH is discussed in terms of its clinical importance and unusual selectivity. Most point mutations of PhyH causing ARD cluster in two distinct groups around the Fe(II)- and 2OG-binding sites. Therapaeutic possibilities for the treatment of Refsum's disease involving PhyH are discussed.
The role of 2-hydroxyacyl-CoA lyase, a thiamin pyrophosphate-dependent enzyme, in the peroxisomal metabolism of 3-methyl-branched fatty acids and 2-hydroxy straight-chain fatty acids
Authors: Casteels M. , Sniekers M. , Fraccascia P. , Mannaerts G.P. , Van Veldhoven P.P.
Published: November 2007

2-Hydroxyphytanoyl-CoA lyase (abbreviated as 2-HPCL), renamed to 2-hydroxyacyl-CoA lyase (abbreviated as HACL1), is the first peroxisomal enzyme in mammals that has been found to be dependent on TPP (thiamin pyrophosphate). It was discovered in 1999, when studying α-oxidation of phytanic acid. HACL1 has an important role in at least two pathways: (i) the degradation of 3-methyl-branched fatty acids like phytanic acid and (ii) the shortening of 2-hydroxy long-chain fatty acids. In both cases, HACL1 catalyses the cleavage step, which involves the splitting of a carbon–carbon bond between the first and second carbon atom in a 2-hydroxyacyl-CoA intermediate leading to the production of an (n−1) aldehyde and formyl-CoA. The latter is rapidly converted into formate and subsequently to CO2. HACL1 is a homotetramer and has a PTS (peroxisomal targeting signal) at the C-terminal side (PTS1). No deficiency of HACL1 has been described yet in human, but thiamin deficiency might affect its activity.
Is there life after plaque rupture?
Authors: Jackson C.L.
Published: November 2007

Little is known of the relationship between plaque rupture and adaptive geometric remodelling, especially in the context of unstable atherosclerosis. We have assessed remodelling in the proximal brachiocephalic arteries of fat-fed apoE (apolipoprotein E)-knockout mice. The rate of vessel expansive remodelling is similar in vessels with plaques and without plaques, suggesting that the presence of plaque is not necessary for remodelling to occur. In vessels with plaques, the degree of expansive remodelling was strongly associated with the stability of the plaque. Vessels with stable plaques (i.e. with neither buried fibrous caps nor acute plaque ruptures) showed no expansion, whereas those with evidence of plaque rupture expanded at a significant rate. Vessels with stable plaques suffered significant loss of lumen over time, but those with unstable plaques maintained lumen area over time. Pravastatin treatment of male apoE-knockout mice caused a 5-fold increase in fibrous cap thickness and, although it did not influence overall rates of vessel remodelling, it significantly increased both the amount of vessel expansion and the period of time between plaque ruptures, suggesting that it increases the ability of the plaque to resist the rupturing force caused by vessel expansion. These results suggest that vessel expansion in brachiocephalic arteries of fat-fed apoE-knockout mouse does not require the presence of plaque. When a plaque is present, the outward remodelling force is exerted across its cap: vessels with smaller outward remodelling forces cannot overcome the strength of the cap, and the plaque remains stable. When the remodelling force is greater than the strength of the cap, the plaque ruptures. Thus plaque rupture can be viewed as a consequence of vessel remodelling. Interventions that strengthen the plaque, such as pravastatin therapy, do not alter remodelling parameters but instead allow for more outward remodelling before a rupture is caused.
The role of stem cells in vein graft remodelling
Authors: Xu Q.
Published: November 2007

The vessel wall is a dynamic tissue that undergoes positive remodelling in response to altered mechanical stress. A typical example is vein graft remodelling, because veins do not develop arteriosclerosis until a vein segment is grafted on to arteries. In this process, it was observed that vascular endothelial and smooth muscle cells of vein grafts die due to suddenly elevated blood pressure. This cell death is followed by endothelial regeneration. Central to this theme is the essential role played by EPCs (endothelial progenitor cells) in regenerating the lost endothelium. The mechanisms by which EPCs attach to the vessel wall and differentiate into mature endothelial cells involve increased chemokine production and laminar shear flow stimulation on the vessel wall. It seems that neo-endothelial cells derived from EPCs lack mature cell functions and express high levels of adhesion molecules resulting in LDL (low-density lipoprotein) penetration and mononuclear cell infiltration into the sub-endothelial space. Among infiltrated mononuclear cells, there are smooth muscle progenitors that proliferate and differentiate into smooth muscle cells. Meanwhile, stem cells present in the media and adventitia may also migrate into arteriosclerotic lesions via the vasa vasorum that are abundant in the diseased vessels. However, the molecular events leading to the homing, differentiation and maturation of stem/progenitor cells still needs elucidation. The present review attempts to update the progress in stem cell research related to the pathogenesis of vein graft arteriosclerosis or remodelling, focusing on the mechanisms by which stem/progenitor cells participate in the development of lesions, and to discuss the controversial issues and the future perspectives surrounding this research area.
The potential roles of sphingolipids in vascular smooth-muscle function
Authors: Nixon G.F. , Mathieson F.A. , Hunter I.
Published: November 2007

Increasing experimental evidence has demonstrated that sphingolipids are likely to have an important regulatory function in the cardiovascular system. Two sphingolipids released from activated platelets, and therefore of particular relevance, are S1P (sphingosine 1-phosphate) and SPC (sphingosylphosphocholine). Both S1P and SPC can act as vasoconstrictors and may modulate VSMC (vascular smooth muscle cell) phenotype, as observed during the pathogenesis of vascular disease. Recent research has suggested that SPC may act as a pro-inflammatory mediator in VSMCs and, in some circumstances, may also contribute to the development of vascular disease.
Prostacyclin analogues: the next drug-eluting stent?
Authors: McCormick C. , Wadsworth R.M. , Jones R.L. , Kennedy S.
Published: November 2007

Recent concern over existing drug-eluting stents, for the treatment of myocardial ischaemia, has led to the development of approaches that seek to inhibit restenosis while promoting the recovery of a functional endothelium. Prostacyclin analogues may be worthy candidates for use within a drug-eluting stent by virtue of their wide profile of vasoprotective effects. This article reviews recent developments in this area, and in so doing, reveals the future challenges for the further development of this technology.
Plasma-membrane calcium pumps and hereditary deafness
Authors: Brini M. , Leva F. Di , Domi T. , Fedrizzi L. , Lim D. , Carafoli E.
Published: November 2007

In mammals, four different genes encode four PMCA (plasma-membrane Ca2+-ATPase) isoforms. PMCA1 and 4 are expressed ubiquitously, and PMCA2 and 3 are expressed predominantly in the central nervous system. More than 30 variants are generated by mechanisms of alternative splicing. The physiological meaning of the existence of so many isoforms is not clear, but evidently it must be related to the cell-specific demands of Ca2+ homoeostasis. Recent studies suggest that the alternatively spliced regions in PMCA are responsible for specific targeting to plasma membrane domains, and proteins that bind specifically to the pumps could contribute to further regulation of Ca2+ control. In addition, the combination of proteins obtained by alternative splicing occurring at two different sites could be responsible for different functional characteristics of the pumps.
Plasma-membrane Ca2+ pumps: structural diversity as the basis for functional versatility
Authors: Strehler E.E. , Filoteo A.G. , Penniston J.T. , Caride A.J.
Published: November 2007

Plasma-membrane calcium pumps [PMCAs (plasma-membrane Ca2+-ATPases)] expel Ca2+ from eukaryotic cells to maintain overall Ca2+ homoeostasis and to provide local control of intracellular Ca2+ signalling. Recent work indicates functional versatility among PMCA isoforms, with specific pumps being essential for cochlear hair cell function, sperm motility, feedback signalling in the heart and pre- and post-synaptic Ca2+ regulation in neurons. The functional versatility of PMCAs is due to differences in their regulation by CaM (calmodulin), kinases and other signalling proteins, as well as to their differential targeting and retention in defined plasma membrane domains. The basis for this is the structural diversity of PMCAs. In mammals, four genes encode PMCA isoforms 1–4, and each of these has multiple variants generated by alternative RNA splicing. The alternatively spliced regions are intimately involved in the regulatory interactions and differential membrane localization of the pumps. The alternatively spliced C-terminal tail acts as an autoinhibitory domain by interacting with the catalytic core of the pump. The degree of inhibition and the kinetics of interaction with the major activator CaM differ between PMCA variants. This translates into functional differences in how PMCAs handle Ca2+ signals of different magnitude and frequency. Accumulating evidence thus demonstrates how structural diversity provides functional versatility in the PMCAs.
Mechanisms of neuronal damage in multiple sclerosis and its animal models: role of calcium pumps and exchangers
Authors: Kurnellas M.P. , Donahue K.C. , Elkabes S.
Published: November 2007

Multiple sclerosis is an inflammatory, demyelinating and neurodegenerative disorder of the central nervous system. Increasing evidence indicates that neuronal pathology and axonal injury are early hallmarks of multiple sclerosis and are major contributors to progressive and permanent disability. Yet, the mechanisms underlying neuronal dysfunction and damage are not well defined. Elucidation of such mechanisms is of critical importance for the development of therapeutic strategies that will prevent neurodegeneration and confer neuroprotection. PMCA2 (plasma-membrane Ca2+-ATPase 2) and the NCX (Na+/Ca2+ exchanger) have been implicated in impairment of axonal and neuronal function in multiple sclerosis and its animal models. As PMCA2 and NCX play critical roles in calcium extrusion in cells, alterations in their expression or activity may affect calcium homoeostasis and thereby induce intracellular injury mechanisms. Interventions that restore normal PMCA2 and NCX activity may prevent or slow disease progression by averting neurodegeneration.
Spatiotemporal control of cAMP signalling processes by anchored signalling complexes
Authors: Jarnæss E. , Taskén K.
Published: November 2007

Ligand-induced changes in cAMP concentration vary in duration, amplitude and extension into the cell. cAMP microdomains are shaped by adenylate cyclases that form cAMP as well as PDEs (phosphodiesterases) that degrade cAMP. Various extracellular signals converge on the cAMP/PKA (protein kinase A) pathway through ligand binding to GPCRs (G-protein-coupled receptors) and the cAMP/PKA pathway is therefore tightly regulated on several levels to maintain specificity in the multitude of signal inputs. AKAPs (A-kinase-anchoring proteins) target PKA to specific substrates and distinct subcellular compartments, providing spatial and temporal specificity for mediation of biological effects channelled through the cAMP/PKA pathway. AKAPs also serve as scaffolding proteins that assemble PKA together with signal terminators such as phosphoprotein phosphatases and cAMP-specific PDEs as well as components of other signalling pathways into multiprotein signalling complexes.
Ubiquitin signals in the NF-κB pathway
Authors: Terzic J. , Marinovic-Terzic I. , Ikeda F. , Dikic I.
Published: November 2007

The NF-κB (nuclear factor κB) transcription factors control cell survival, proliferation and innate and adaptive immune response. Post-translational modifications of key components of the NF-κB pathway provide the molecular basis for signal transmission from the cell membrane to the nucleus. Here, we describe the involvement of different types of ubiquitin modification in the regulation of the NF-κB signalling pathway.
Rapid discovery of protein interactions by cell-free protein technologies
Authors: He M. , Taussig M.J.
Published: November 2007

Cell-free transcription and translation provides an open, controllable environment for production of correctly folded, soluble proteins and allows the rapid generation of proteins from DNA without the need for cloning. Thus it is becoming an increasingly attractive alternative to conventional in vivo expression systems, especially when parallel expression of multiple proteins is required. Through novel design and exploitation, powerful cell-free technologies of ribosome display and protein in situ arrays have been developed for in vitro production and isolation of protein-binding molecules from large libraries. These technologies can be combined for rapid detection of protein interactions.
Insights into the structure and protein–protein interactions of the pro-apoptotic protein ASPP2
Authors: Rotem S. , Katz C. , Friedler A.
Published: November 2007

ASPP (apoptosis-stimulating protein of p53) 2 is a pro-apoptotic protein that stimulates the p53-mediated apoptotic response. Here, we provide an overview of the structure and protein–protein interactions of ASPP2. The C-terminus of ASPP2 contains Ank (ankyrin) repeats and an SH3 domain (Src homology 3 domain). The Ank–SH3 domains mediate interactions between ASPP2 and numerous proteins involved in apoptosis such as p53 and Bcl-2. The proline-rich domain of ASPP2 is unfolded in its native state, but was not shown to mediate intermolecular interactions. Instead, it makes an intramolecular domain–domain interaction with the Ank–SH3 C-terminal domains of ASPP2. This intramolecular interaction between the unstructured proline-rich domain and the structured Ank–SH3 domains in ASPP2, which is possible due to the unfolded nature of the proline-rich domain, is proposed to have an important role in regulating the intermolecular interactions of ASPP2 with its partner proteins.
Picking pockets to fuel antimicrobial drug discovery
Authors: Hunter W.N.
Published: November 2007

The inhibition of essential enzymes in microbial pathogens offers a route to treatment of infectious diseases. However, although the biology of the organism dictates a need for a particular enzyme activity, this does not necessarily mean that the enzyme is a good drug target. The chemistry of the active site (size, shape and properties) determines the likelihood of finding a molecule with the right properties to influence drug discovery. Discriminating between good and less-good targets is important. Studies on enzymes involved in the regulation of oxidative stress and pterin/folate metabolism of trypanosomatid parasites and isoprenoid precursor biosynthesis in bacteria and apicomplexan parasites illustrates a range of active sites representing those that are challenging with respect to the discovery of potent inhibitors, to others that provide more promising opportunities in drug discovery.
Protein kinase Cδ and apoptosis
Authors: Reyland M.E.
Published: November 2007

The PKC (protein kinase C) family regulates diverse cellular functions and specific isoforms have been shown to be critical regulators of cell proliferation and survival. In particular, PKCδ is known to be a critical pro-apoptotic signal in many cell types. Work in our laboratory has focused on understanding the molecular mechanisms through which PKCδ regulates apoptosis and on how the pro-apoptotic activity of this ubiquitous kinase is regulated such that cells only activate the apoptotic cascade when appropriate. We have identified multiple regulatory steps that activate the pro-apoptotic function of PKCδ in response to genotoxins. Our studies show that apoptotic signals induce rapid post-translational modification of PKCδ in the regulatory domain, which facilitates translocation of the kinase from the cytoplasm to the nucleus. Active caspase 3 also accumulates in the nucleus under these conditions, resulting in caspase cleavage of PKCδ and generation of a constitutively activated form of PKCδ [δCF (PKCδ catalytic fragment)]. In contrast with PKCδ, δCF is constitutively present in the nucleus, and this nuclear accumulation of PKCδ is essential for apoptosis. Thus our studies suggest that tight regulation of nuclear import and of PKCδ is critical for cell survival and that caspase cleavage of PKCδ in the nucleus signals an irreversible commitment to apoptosis.