bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and thermal evolution of the Karakoram crust
Authors: SEARLE M. P. , TIRRUL R.
Published: December 2007

Prior to the Eocene (c. 50 Ma) collision of the Indian and Asian plates, the southern margin of Asia along the Karakoram plate was an Andean-type margin dominated by tonalitic-granodioritic magmatism of Jurassic––Lower Cretaceous age (Hushe gneiss, Muztagh Tower gneiss and K2 ortho-gneiss) and associated low pressure andalusite, staurolite and garnet grade metamorphism (M1). Following India-Asia collision, crustal shortening, thickening and regional Barrovian metamorphism (M2) occurred between 50–37 Ma. Thermobarometry of kyanite-grade metapelites indicate burial to depths of around 30–35 km. Simultaneous solution of the garnet-biotite geothermometer with the garnet-muscovite-biotite-plagioclase and garnet-AI
2
, SiO
5
,-quartz-plagioclase geobarometers indicates peak M2
P
-
T
conditions of 696±20°C at 8.6±0.7kbar (860 MPa). Temperatures may have exceeded 700 °C in sillimanite-grade metapelites to produce in situ partial melting and leucogranitic melt pods. Peak M2 metamorphism occurred prior to 37 ±0.8 Ma, the crystallization age of the Mango Gusar two-mica granite pluton which cross-cuts syn-metamorphic deformation fabrics.

Post-M2 thermal relaxation followed from 37–25 Ma, after which localized high heat concentrations at the base of the thickened crust caused widespread crustal melting and intrusion of the Baltoro granite batholith at 25–21 Ma. A high temperature-low pressure thermal aureole (M3) along the northern contact is synchronous with the 21 ±0.5 Ma zircon age of the Baltoro granite. Andalusite hornfels along the northern contact of the batholith (Mitre thermal aureole) indicates maximum pressures of 3.75 kbar (375 MPa). A 75 °C increase of temperature in kyanite-sillimanite grade gneisses approaching the southern granite contact of the Baltoro granite is interpreted as the thermal upwarping of pre-37 Ma Barrovian metamorphic M2 isograds around the 21 Ma contact aureole M3 isotherms.
Hercynian tectonometamorphic evolution of the Bosost dome (French–Spanish central Pyrenees)
Authors: POUGET P.
Published: December 2007

Metamorphic and structural studies show that the Bosost dome (Central Pyrenees) is a metamorphic as well as a structural dome developed in Cambro-Ordovician to Devonian metasediments around a migmatitic core during the Hercynian orogeny. The structural-metamorphic dome occurs in epizonal terranes, and is twice as large as originally described. The structural dome shows a concentric zoning of D2 and D3 local deformations developed around the migmatites and superimposed on the D1 regional Hercynian deformation. The structural data suggest that migmatites were emplaced diapirically into Palaeozoic metasediments during D1, and are responsible for the local D2 and D3 deformations. An early medium pressure–high temperature metamorphism occurred during D1, leading to anatexis under water-rich conditions, then evolved progressively to a high temperature-low pressure metamorphism during the D2 and D3 deformations. The corresponding
P–T
-time path is a clockwise loop representing the evolution of the metamorphism, from migmatiza-tion to the diapiric emplacement of migmatites, in a compressional setting. Pressure values obtained from geobarometry are three times as high as expected from sedimentological data. This suggests that the Hercynian metamorphism developed in a thickened crust during the N-S shortening responsible for the large-scale E–W folding observed throughout the Pyrenean Axial Zone.
Petroleum geology and basin development on the North West Seaboard
Authors: PARNELL J.
Published: December 2007

Report of a meeting of the British Sedimentological Research Group of the Geological Society held at the Queen's University of Belfast on 25–28 September 1990. The organizers were J. Parnell and B. Monson.

There is currently much interest in the extensive series of basins stretching from west of Shetland through the Hebrides to Northern Ireland and the west coast of Ireland. Each of these regions has seen drilling activity as part of hydrocarbon exploration programmes. The meeting was convened to review research into the development of basins of Carboniferous to Tertiary age on the northwestern seaboard of the British Isles. Twenty eight papers were presented, followed by a two-day field excursion to examine basins in the north of Ireland.

W. I. Mitchell
(Geological Survey, N. Ireland) discussed the evolution of Carboniferous basins in north west Ireland, and particularly of the Fintona Block, a series of fault-bounded tracts of Devonian—Carboniferous red beds. The northwards migration of the early Carboniferous marine transgression was associated with a sequential propagation of back-stepping faults and the development of diachronous facies belts of Courceyan-Arundian age.
M. E. Philcox
(Consultant, Co. Wicklow),
G. Clayton, G. D. Sevastapulo and H. Baily
reported stratigraphic data for the Dinantian Lough Allen Basin in north west Ireland, incorporating information from a gas exploration programme by Aran Energy. Basin evolution was partially fault-controlled, and some faults were later reactivated during Hercynian deformation.
B. Mown
(Queen's Univ., Belfast) presented a reconstruction for the burial history of Carboniferous rocks in north west Ireland
ESR studies for absolute dating of fault movements
Authors: FUKUCHI TATSURO
Published: December 2007

The principle of absolute dating of fault movements is based on the initialization or resetting of some ‘clock’ system by faulting. In the case of ESR dating, heating is more effective in resetting ESR signals than fracturing. According to a computer simulation of resetting by shear heating during faulting, the ESR signals can never be completely reset at depths of less than 100–200 m below the surface of the earth. Therefore, ESR samples must be collected from depth by coring or tunnelling, or from outcrop, with consideration of the rate of exhumation of the fault outcrop. In general, unpaired electrons trapped at lattice defects in crystals can diffuse much more easily than atoms, hence samples for other dating methods, which are based on the diffusion of atoms, should be collected at even greater depth. On the other hand, if no ESR signal is observed from unfractured quartz in the wall rocks, one may directly determine the age of the fault movement using ESR signals in the fractured quartz whose precursors were formed by faulting. The age obtained (
T
) should then satisfy the following relationship: T
b
≥
T
≥
T

e

,
where
T

b

and
T

e

are the ages of the beginning and end of the fault movements, and it may show the time of a fault movement.
The saline waters of Llandrindod and Builth, Central Wales
Authors: EDMUNDS W. M. , ROBINS N. S. , SHAND P.
Published: December 2007

Saline or brackish mineral waters have been recorded at several locations in mid-Wales and the Welsh borderlands. The main groups are centered on Llandrindod Wells and Builth Wells where maximum salinities of 5340 and 16 380 mg l
−1
respectively are found. The total discharge from these springs is very low (combined 2 l s
−1
) yet their flow remains almost constant. Residence times of several thousand years are derived using
14
C analysis, and δ
18
O and δ
2
H results suggest that the waters at Llandrindod (although not at Builth) contain a component of Late Pleistocene water. Evidence from the Br/Cl ratios and trace elements indicates that the origin of the salinity lies within the Lower Palaeozoic formations and has not been derived from evaporites. The mineral waters have undergone complete reduction of sulphate which has led to high concentrations of Ba (maximum 53.2 mg l
−1
) at Llangammarch Wells. The most likely origin of these waters is the deep circulation of meteoric water over a residence time of several thousand years which has risen slowly along minor fracture systems to the points of outlet. The interconnected fracture storage of these waters implied from the various lines of evidence must be of the order >30 Mm
3
.
Sedimentology, geochronology and provenance of the Proterozoic Itremo Group, central Madagascar, and implications for pre-Gondwana palaeogeography
Authors: COX RÓNADH , ARMSTRONG RICHARD A. , ASHWAL LEWIS D.
Published: December 2007

Proterozoic metasediments of the Itremo Group in central Madagascar probably represent a passive margin sequence predating Gondwana assembly. The quartzites are well-sorted quartz arenites that contain flat lamination, wave ripples, current ripple cross-lamination, and dune cross bedding. The carbonate rocks preserve abundant stromatolites and algal laminates. A continental source is indicated by mudrock major and trace element chemistry. The combination of lithologic association, sediment architecture and mudrock chemistry indicates that the sequence was deposited on a continental shelf or platform.

SHRIMP data from detrital zircons indicate that the source area included early Proterozoic and late Archean rocks with ages between 1.85 and 2.69 Ga, and that the depositional age of the Itremo Group must be less than 1855 ± 11 Ma. The sequence has been deformed into a series of large-scale folds separated by ductile shear zones. SHRIMP data indicate both massive lead loss from detrital zircons and new zircon growth in the metasediments at 833 ± 112 Ma, which we interpret as the age of metamorphism of the sequence. Comparison of detrital grain ages with basement ages in East Africa and in India indicates that the source area for the Itremo Group probably lay on the present African mainland.
Emplacement of rapakivi granite and syenite by floor depression and roof uplift in the Palaeoproterozoic Ketilidian orogen, South Greenland
Authors: GROCOTT J. , GARDE A. A. , CHADWICK B. , CRUDEN A. R. , SWAGER C.
Published: December 2007

In the Palaeoproterozoic Ketilidian orogen of South Greenland, tabular intrusions of the rapakivi granite suite exposed at Graah Fjelde, Lindenow Fjord and Qernertoq, and a Mesoproterozoic syenite of the Gardar province exposed at Paatusoq, were emplaced by a combination of roof uplift and floor depression. The strain associated with the emplacement of the intrusions mainly involved redistribution of mass vertically within the lithosphere. Space for the emplacement of the rapakivi plutons was not created during regional extension on low-angle, ductile shear zones as claimed by some previous workers and there is no evidence that emplacement of the intrusions coincided with extensional collapse of the orogen following crustal thickening. The rapakivi granites post-date peak metamorphism in the orogen by 35–46 Ma and their contacts cross-cut and clearly post-date intense, flat-lying D1/D2 fabrics that formed by partitioning of deformation into arc-normal and arc-parallel components during oblique convergence.
Central subsidence in the layered Hypersthene-gabbro of Centre II, Ardnamurchan, Argyllshire
Authors: Skelhorn Raymond Richard , Elwell Royston William Dunlop
Published: December 2007

The layering in the Hypersthene-gabbro of Centre II, Ardnamurchan has been mapped in as much detail as possible. The dips are confocal and steepen inwards, up to more than 50°, towards a central area occupied by later intrusions. The pattern of confocal dips is incomplete, partly because the eastern half of the gabbro has been cut out by Centre III intrusions and partly because the gabbro is not rhythmically layered throughout. There is convincing evidence that the layering was produced by bottom accumulation on successive floors which were more or less horizontal, so that the inward steepening must be due to later deformation. It is considered that the deformation concerned represents a downbending produced by movement on a ring fault, which is now obliterated. This process of cauldron subsidence dropped the central part of the gabbro to a lower level and permitted the emplacement of the next intrusion in the Centre II sequence, the granophyric quartz-dolerite. From a survey of the literature it would appear that there are other gabbros for which the attitude of the layering shows a pattern which we think may have been produced by cauldron subsidence.
A Precambrian conglomerate with an amphibolite matrix near Kaladar, Ontario
Authors: van de Kamp Peter Cornelis
Published: December 2007

The mineralogy and chemistry of the amphibolitic matrix of a metamorphosed Precambrian conglomerate throw light on the derivation of the deposit from eroded basic and acid igneous parent rocks. Chemical analyses for 31 elements in 25 samples illustrate the mafic nature of the conglomerate matrix and show the influence of both basic and acid source types. Indicative of basic source rocks are high Mg, Fe, Cr, Ni, and low Si. Acid rock contributions are recognized by high K and Rb (present in K-feldspar and biotite).

The conglomerate is a peculiar type of metasedimentary amphibolite quite unlike ‘normal’ hornblende-plagioclase amphibolites of meta-igneous origin or the para-amphibolites from Ontario and Scotland previously described. It does not however have a unique composition amongst coarse clastic rocks and similar examples from other locations are cited. Such clastic rocks are probably all first cycle alluvial or fluvial deposits from source areas rich in mafic rocks.
Tillite horizons in the Chamba Himalayas of Himachal Pradesh, North India
Authors: Powell Derek , Saxena Mahendra
Published: December 2007

Two
extensive
exposures of tillite of probable Lower Carboniferous age occur on Highway 37 between Bharmaur and Tissa, Himachal Pradesh. One lies eight kilometres south of the village of Kalhal, the other five kilometres west of Durgatti (Fig. 1). The two sections lie some fifty kilometres apart along the strike and are between three areas where tillites have previously been recognized, namely, Salt Range, Kashmir and Simla.

Lithology and texture

The tillites in both localities occur within a succession ascribed by McMahon (1883) to the Silurian System. Both comprise grey phyllites containing cobbles, pebbles and sand size grains. The larger clasts are completely surrounded by the matrix Plate 1 and their concentration varies from beds with only one or two cobbles and/or pebbles per square metre, to beds which resemble a polymict conglomerate. The larger fragments are angular to sub-rounded but intense, penetrative deformation has considerably modified original shapes. The tillites are strongly schistose and usually bedding cannot be distinguished. In more conglomeratic horizons, however, bedding is reflected by changes in the concentration of fragments. The clasts are of pure white quartzite, buff limestone and grey phyllite. No igneous or strongly metamorphosed rocks occur.

The ill-sorted nature of the deposits is confirmed in thin section where the matrix consists of single crystal fragments of quartz, calcite and occasional feldspar set in finer mica, quartz, calcite and opaque ore. Recrystallization of mica and ore has occurred and quartz frequently exhibits syntaxial growth rims.

In both localities the tillites are associated with
Structurally complex reservoirs: an introduction
Authors: Jolley S. J. , Barr D. , Walsh J. J. , Knipe R. J.
Published: December 2007

Structurally complex reservoirs form a distinct class of reservoir, in which fault arrays and fracture networks, in particular, exert an over-riding control on petroleum trapping and production behaviour. With modern exploration and production portfolios commonly held in geologically complex settings, there is an increasing technical challenge to find new prospects and to extract remaining hydrocarbons from these more structurally complex reservoirs. Improved analytical and modelling techniques will enhance our ability to locate connected hydrocarbon volumes and unswept sections of reservoir, and thus help optimize field development, production rates and ultimate recovery. This volume reviews our current understanding and ability to model the complex distribution and behaviour of fault and fracture networks, highlighting their fluid compartmentalizing effects and storage-transmissivity characteristics, and outlining approaches for predicting the dynamic fluid flow and geomechanical behaviour of structurally complex reservoirs. This introductory paper provides an overview of the research status on structurally complex reservoirs and aims to create a context for the collection of papers presented in this volume and, in doing so, an entry point for the reader into the subject. We have focused on the recent progress and outstanding issues in the areas of: (i) structural complexity and fault geometry; (ii) the detection and prediction of faults and fractures; (iii) the compartmentalizing effects of fault systems and complex siliciclastic reservoirs; and (iv) the critical controls that affect fractured reservoirs.
A damage domain approach to integration of geomechanics and seismic anisotropy for fractured reservoir characterization
Authors: Hall S. A. , Lewis H.
Published: December 2007

The concepts of damage mechanics are proposed as the logical basis for integration of seismic anisotropy based identification and geomechanics based prediction of subsurface fracturing. In such a context a damage tensor can be used to describe the evolution of (anisotropic) degradation of the elastic properties of a rock undergoing deformation. The concepts of damage mechanics are common to both geomechanical and seismic descriptions of rock elasticity but have not previously been connected. In geomechanical simulations of the evolution of geological structures, damage development can be predicted, described and recorded through a single damage tensor representation for each point in the model (with the inclusion of damage by a number of different mechanisms). With appropriate analysis, equivalent information may be determined from anisotropy analysis of seismic reflection data as the seismic wave propagation is sensitive to the total damage. Thus the proposed approaches for parameterization and modelling/analysis, using the damage domain, provide a common quantification of the damage (as detected using seismic data and predicted using geomechanical modelling) that permits integration of the two disciplines. This paper presents the damage-domain theory and linkage between the domains plus practicalities, with respect to both the geomechanical and seismic analyses, with illustration using a simple geomechanical model example.
Stratigraphic control on extensional fault propagation folding: Big Brushy Canyon monocline, Sierra Del Carmen, Texas
Authors: Ferrill D. A. , Morris A. P. , Smart K. J.
Published: December 2007

Mechanical stratigraphy exerts a first-order control on deformation at a range of scales from oilfield-scale structural style to deformation (e.g. fracturing) within an individual reservoir stratum. This paper explores an outcrop example where mechanical stratigraphy in a limestone and shale sequence directly influenced the structural style and distribution of deformation related to the propagation of a ‘seismic-scale’ normal fault that has maximum displacement on the order of 100–500 m and extends for more than 10 km. A monocline developed in Cretaceous Buda Limestone above tectonically thinned Del Rio Clay and faulted Santa Elena Limestone is here interpreted as an extensional fault propagation fold. Monocline limb dips reach 59°. The Del Rio Clay is thinned from approximately 36 m to 1.5 m, whereas the underlying Santa Elena Limestone is offset vertically by approximately 74 m along a steep (approximately 80°) normal fault. This large fault displacement of the Santa Elena Limestone is not transferred upward to the Buda Limestone because of ductile flow within the intervening Del Rio Clay. Although upward fault propagation has been inhibited, thinning of the Del Rio Clay and the resultant extreme displacement gradient at the tip of the fault have forced the Buda Limestone into a monoclinal fold. Two competent packstone and grainstone beds, 6 m and 2.7 m thick and separated by 10.5 m of less competent calcareous shale, comprise the Buda Limestone at this location. Deformation features within the competent Buda beds include bed-perpendicular veins that accommodate bed-parallel extension, and bedding plane slip surfaces with an up-dip sense of shear that offset the veins. Deformation is concentrated in the monoclinal limb and not in the monoclinal hinge regions. Consequently, bed-parallel extension and shear strain are associated with monoclinal dip, not with curvature. These results show that for this structure, bed dip is a better proxy for bed-parallel extension and related fracture dilation than is curvature.
Incorporation of fault properties into production simulation models of Permian reservoirs from the southern North Sea
Authors: Zijlstra E. B. , Reemst P. H. M. , Fisher Q. J.
Published: December 2007

Reservoir compartmentalization is one of the key issues that affects the development and production phase of gas fields. To improve prediction of the effects of compartmentalization on production, a new method has been developed to allow petroleum engineers to incorporate geologically-reasonable fault rock flow properties into upscaled dynamic reservoir simulation models. The first stage of the workflow is to estimate the permeability and capillary characteristics of fault rocks within the field. These data are then combined with estimates of fault rock thickness, derived from outcrop studies, to calculate transmissibility multipliers to take into account the impact of faults on fluid flow within the dynamic model. Our method differs from most others in that we have attempted to account for the two-phase flow properties of fault rocks in the dynamic models from producing reservoirs. Application of the model to real field examples provides far faster history matching than has been achieved previously. In addition, taking into account the multi-phase flow properties of fault rocks explains production behaviour that previous models could not. Although, the focus of this study has been on the Southern Permian Basin in the North Sea, the same approach could be applied to other areas.
The link between a heterogeneous model and its flow response: examples from fault damage zones highlighting issues in domain discretization and flow simulation
Authors: Ma J. , Vaszi A. Z. , Couples G. D. , Harris S. D.
Published: December 2007

Natural fault damage zones (FDZs) are characterized by complex geometries and topologies, and by strongly-contrasting material properties. Accurate simulation of fluid flow in such systems is dependent on the method of discretization and the mathematical representation of the flow. In this paper, we focus on the conceptual and methodological issues that link a model of a heterogeneous system and its flow response. We study FDZs as our example, where each thin fault strand is a barrier to flow. We examine two contrasting discretization schemes and apply them to 2D FDZ models that contain a realistic array of linear fault traces. Both schemes produce results that are generally in good agreement, and agree with the results calculated by a more accurate (but computationally less efficient) reference scheme. However, differences occur when the discretization approach fails to maintain the fault connectivity (topology) of the input model. It is important to guide the modelling by identifying any continuous flow pathways in the matrix linking fluid inlets and outlets (Through-Going Regions, TGRs). We illustrate a new scheme that identifies all TGRs and determines a grid that is just fine enough to resolve them.
Editing faults within tetrahedral volume models in real time
Authors: Tertois A. L. , Mallet J. L.
Published: December 2007

Accurately positioning faults in a geological model is a major concern because they are responsible for offsets of geological sequences. In the tetrahedral models studied in this paper, faults are discontinuities: faces of tetrahedra on either side of a fault are disconnected. Building tetrahedral models can require a large amount of time, especially when there are many faults. We present a tool for making small, real-time, modifications of faults in tetrahedral models arising from geometrical changes required either by new subsurface data or by new interpretations of existing subsurface data. Fault editing is achieved by moving control points on the fault in the tetrahedral grid and by computing a distortion property over an editable volume relative to the control point and spreading this distortion to neighbouring points using the Discrete Smooth Interpolation technique. The editable volume in which tetrahedron vertices are allowed to move is defined by a given distance to the fault. This approach provides a means of editing faults and fault-related features, such as branch-lines.
Kinematically-equivalent but geomechanically-different simulations of fault evolution: the role of loading configurations
Authors: Lewis H. , Hall S. A. , Guest J. , Couples G. D.
Published: December 2007

Geomechanical simulations are used to demonstrate the importance of the way that models are loaded. In this paper the development of permanent damage during faulting using frictional-slip models of a reverse fault is investigated. Although the use of different loads and constraints can produce the same faulted geometry (for the same rock type, and at the same burial depth), the models develop very different stress and strain states. Permanent strain magnitudes and distributions between models are quite dissimilar, including the distributions of permanent dilation and compaction. This work demonstrates that boundary loads and boundary constraints are significant factors in determining what stress and deformation states evolve in the simulation model. The examples also illustrate that final (deformed) geometry alone is a very poor basis from which to predict either stress state or open fracture distribution. Bulk finite strain does not allow a prediction of local principal stress directions, magnitudes, or signs, at least in the vicinity of fault damage zones.
Modulation of the Kir7.1 potassium channel by extracellular and intracellular pH
Authors: Hughes Bret A. , Swaminathan Anuradha
Published: December 2007

Inwardly rectifying K+ (Kir) channels in the apical membrane of the retinal pigment epithelium (RPE) contribute to extracellular K+ homeostasis in the distal retina by mediating K+ secretion. Multiple lines of evidence suggest that these channels are composed of Kir7.1. Previously, we showed that native Kir channels in bovine RPE are modulated by changes in intracellular pH in the physiological range. In the present study, we used the Xenopus laevis oocyte expression system to investigate the pH dependence of cloned human Kir7.1 channels and several point mutants involving histidine residues in the NH2 and COOH termini. Kir7.1 channels were inhibited by strong extracellular acidification and modulated by intracellular pH in a biphasic manner, with maximal activity at about intracellular pH (pHi) 7.0 and inhibition by acidification or alkalinization. Replacement of histidine 26 (H26) in the NH2 terminus with alanine eliminated the requirement of protons for channel activity and increased sensitivity to proton-induced inhibition, resulting in maximal channel activity at alkaline pHi and smaller whole cell currents at resting pHi compared with wild-type Kir7.1. When H26 was replaced with arginine, the pHi sensitivity profile was similar to that of the H26A mutant but with the p Ka shifted to a more acidic value, giving rise to whole cell current amplitude at resting pHi that was comparable to that of wild-type Kir7.1. These results indicate that Kir7.1 channels are modulated by intracellular protons by diverse mechanisms and suggest that H26 is important for channel activation at physiological pHi and that it influences an unidentified proton-induced inhibitory mechanism.
Reduced volume but increased training intensity elevates muscle Na+-K+ pump α1-subunit and NHE1 expression as well as short-term work capacity in humans
Authors: Iaia F. Marcello , Thomassen Martin , Kolding Helle , Gunnarsson Thomas , Wendell Jesper , Rostgaard Thomas , Nordsborg Nikolai , Krustrup Peter , Nybo Lars , Hellsten Ylva , Bangsbo Jens
Published: December 2007

The present study examined muscle adaptations and alterations in work capacity in endurance-trained runners after a change from endurance to sprint training. Fifteen runners were assigned to either a sprint training (ST, n = 8) or a control (CON, n = 7) group. ST replaced their normal training by 30-s sprint runs three to four times a week, whereas CON continued the endurance training (∼45 km/wk). After the 4-wk sprint period, the expression of the muscle Na+-K+ pump α1-subunit and Na+/H+-exchanger isoform 1 was 29 and 30% higher ( P < 0.05), respectively. Furthermore, plasma K+ concentration was reduced ( P < 0.05) during repeated intense running. In ST, performance in a 30-s sprint test, Yo-Yo intermittent recovery test, and two supramaximal exhaustive runs was improved ( P < 0.05) by 7, 19, 27, and 19%, respectively, after the sprint training period, whereas pulmonary maximum oxygen uptake and 10-k time were unchanged. No changes in CON were observed. The present data suggest a role of the Na+-K+ pump in the control of K+ homeostasis and in the development of fatigue during repeated high-intensity exercise. Furthermore, performance during intense exercise can be improved and endurance performance maintained even with a reduction in training volume if the intensity of training is very high.
Isoform specificity of Na-K-ATPase-mediated ouabain signaling
Authors: Pierre Sandrine V. , Sottejeau Yoann , Gourbeau Jean-Michel , Sánchez Gladis , Shidyak Amjad , Blanco Gustavo
Published: December 2007

The ion transporter Na-K-ATPase functions as a cell signal transducer that mediates ouabain-induced activation of protein kinases, such as ERK. While Na-K-ATPase composed of the α1-polypeptide is involved in cell signaling, the role of other α-isoforms (α2, α3, and α4) in transmitting ouabain effects is unknown. We have explored this using baculovirus-directed expression of Na-K-ATPase polypeptides in insect cells and ERK phosphorylation as an indicator of ouabain-induced signaling. Ouabain addition to Sf-9 cells coexpressing Na-K-ATPase α1- and β1-isoforms stimulated ERK phosphorylation. In contrast, expression of the α1- and β1-polypeptides alone resulted in no effect, indicating that the αβ-complex is necessary for Na-K-ATPase signaling. Moreover, the ouabain effect was sensitive to genistein, suggesting that Na-K-ATPase-mediated tyrosine kinase activation is a critical event in the intracellular cascade leading to ERK phosphorylation. In addition, the Na-K-ATPases α3β1- and α4β1-isozymes, but not α2β1, responded to ouabain treatment. In agreement with the differences in ouabain affinity of the α-polypeptides, α1β1required 100- to 1,000-fold more ouabain to signal than did α4β1and α3β1, respectively. These results confirm the role of the Na-K-ATPase in ouabain signal transduction, show that there are important isoform-specific differences in Na-K-ATPase signaling, and demonstrate the suitability of the baculovirus expression system for studying Na-K-ATPase-mediated ouabain effects.
Zinc Potentiates Neuronal Nicotinic Receptors by Increasing Burst Duration
Authors: Hsiao Bernard , Mihalak Karla B. , Magleby Karl L. , Luetje Charles W.
Published: December 2007

Micromolar zinc potentiates neuronal nicotinic acetylcholine receptors (nAChRs) in a subtype-dependent manner. Zinc potentiates receptor function even at saturating agonist concentrations, without altering the receptor desensitization rate. Potentiation could occur through an increase in the number of available receptors, an increase in single-channel current amplitude, or an increase in single-channel open probability. To distinguish among these possibilities, we examined rat neuronal nAChRs expressed in Xenopus oocytes. Blockade of a large fraction of ACh activated α4β4 or α4β2 receptors by the open channel blocker hexamethonium failed to change the extent of potentiation by zinc, suggesting that zinc does not change the number of available receptors. The single-channel amplitudes of ACh (1 μM) activated α4β4 receptors in outside-out patches were similar in the absence and the presence of 100 μM zinc (3.0 ± 0.1 and 2.9 ± 0.1 pA, respectively). To determine the effect of zinc on single-channel open probability, we examined α4β4 receptors in cell-attached patches. The open probability at 100 nM ACh (0.011 ± 0.002) was increased 4.5-fold by 100 μM zinc (0.050 ± 0.008), accounting for most of the potentiation observed at the whole cell level. The increase in open probability was due to an increase in burst duration, which increased from 207 ± 38 ms in the absence of zinc to 830 ± 189 ms in the presence of zinc. Our results suggest that potentiation of neuronal nAChRs by zinc is due to a stabilization of the bursting states of the receptor.
BRCA1 Mutation and Young Age Predict Fast Breast Cancer Growth in the Dutch, United Kingdom, and Canadian Magnetic Resonance Imaging Screening Trials
Authors: Tilanus-Linthorst Madeleine M.A. , Obdeijn Inge-Marie , Hop Wim C.J. , Causer Petrina A. , Leach Martin O. , Warner Ellen , Pointon Linda , Hill Kimberley , Klijn Jan G.M. , Warren Ruth M.L. , Gilbert Fiona J.
Published: December 2007

Purpose: Magnetic resonance imaging (MRI) screening enables early detection of breast cancers in women with an inherited predisposition. Interval cancers occurred in women with a BRCA1 mutation, possibly due to fast tumor growth. We investigated the effect of a BRCA1 or BRCA2 mutation and age on the growth rate of breast cancers, as this may influence the optimal screening frequency.

Experimental Design: We reviewed the invasive cancers from the United Kingdom, Dutch, and Canadian MRI screening trials for women at hereditary risk, measuring tumor size at diagnosis and on preceding MRI and/or mammography. We could assess tumor volume doubling time (DT) in 100 cancers.

Results: Tumor DT was estimated for 43 women with a BRCA1 mutation, 16 women with a BRCA2 mutation, and 41 women at high risk without an identified mutation. Growth rate slowed continuously with increasing age (P = 0.004). Growth was twice as fast in BRCA1 (P = 0.003) or BRCA2 (P = 0.03) patients as in high-risk patients of the same age. The mean DT for women with BRCA1/2 mutations diagnosed at ages ≤40, 41 to 50, and >50 years was 28, 68, and 81 days, respectively, and 83, 121, and 173 days, respectively, in the high-risk group. Pathologic tumor size decreased with increasing age (P = 0.001). Median size was 15 mm for patients ages ≤40 years compared with 9 mm in older patients (P = 0.003); tumors were largest in young women with BRCA1 mutations.

Conclusion: Tumors grow quickly in women with BRCA1 mutations and in young women. Age and risk group should be taken into account in screening protocols.
Estrogen Receptor Status Could Modulate the Genomic Pattern in Familial and Sporadic Breast Cancer
Authors: Melchor Lorenzo , Honrado Emiliano , Huang Jia , Álvarez Sara , Naylor Tara L. , García María J. , Osorio Ana , Blesa David , Stratton Michael R. , Weber Barbara L. , Cigudosa Juan C. , Rahman Nazneen , Nathanson Katherine L. , Benítez Javier
Published: December 2007

Purpose: Familial breast cancer represents 5% to 10% of all breast tumors. Mutations in the two known major breast cancer susceptibility genes, BRCA1 and BRCA2, account for a minority of familial breast cancer, whereas families without mutations in these genes (BRCAX group) account for 70% of familial breast cancer cases.

Experimental Design: To better characterize and define the genomic differences between the three classes of familial tumors and sporadic malignancies, we have analyzed 19 BRCA1, 24 BRCA2, and 31 BRCAX samples from familial breast cancer patients and 19 sporadic breast tumors using a 1-Mb resolution bacterial artificial chromosome array-based comparative genomic hybridization.

Results: We found that BRCA1/2 tumors showed a higher genomic instability than BRCAX and sporadic cancers. There were common genomic alterations present in all breast cancer groups, such as gains of 1q and 16p or losses of 8ptel-p12 and 16q. We found that the presence/absence of the estrogen receptor (ER) may play a crucial role in driving tumor development through distinct genomic pathways independently of the tumor type (sporadic or familial) and mutation status (BRCA1 or BRCA2). ER− tumors presented higher genomic instability and different altered regions than ER+ ones.

Conclusions: According to our results, the BRCA gene mutation status (mainly BRCA1) would contribute to the genomic profile of abnormalities by increasing or modulating the genome instability.
Delta-like 4/Notch Signaling and Its Therapeutic Implications
Authors: Yan Minhong , Plowman Greg D.
Published: December 2007

Intense research efforts have been focused toward the identification of regulators of angiogenesis and the development of antiangiogenesis-based cancer therapies. The approval of anti–vascular endothelial growth factor (VEGF) monoclonal antibody (bevacizumab) for use in colorectal and lung cancer provides clinical validation for targeting angiogenesis for the treatment of cancer. Delta-like 4 (Dll4)–mediated Notch signaling represents another key pathway essential for vascular development. Recent studies yield substantial insights into the role of Dll4 in angiogenesis. Dll4 is downstream of VEGF signaling and its activation triggers a negative feedback that restrains the effects of VEGF. Attenuation of Dll4/Notch signaling results in chaotic vascular network with excessive branching and sprouting. In preclinical studies, blocking of Dll4/Notch signaling is associated with a paradoxical increase in tumor vessel density, yet causes marked growth inhibition due to functionally defective vasculature. Dll4 blockade holds promise as an additional strategy for angiogenesis-based cancer therapy, especially when resistance to and/or escape from existing therapies evolve.
Tumors Established with Cell Lines Selected for Oxaliplatin Resistance Respond to Oxaliplatin if Combined with Cetuximab
Authors: Prewett Marie , Deevi Dhanvanthri S. , Bassi Rajiv , Fan Fan , Ellis Lee M. , Hicklin Daniel J. , Tonra James R.
Published: December 2007

Purpose: To establish whether cetuximab, a chimeric IgG1 antibody targeting epidermal growth factor receptor, has the potential to restore responsiveness to oxaliplatin in preclinical cancer models, as has been shown with irinotecan in irinotecan refractory metastatic colorectal cancer patients.

Experimental Design: The effects of cetuximab and oxaliplatin, alone or in combination, were tested in vitro and in vivo using human colorectal cancer cell lines selected for oxaliplatin resistance, as well as parental control cell lines. Evaluations were made of subcutaneous xenograft tumor growth in nu/nu athymic mice, as well as activation of mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2) and AKT, expression of DNA repair genes, density of apurinic/apyrimidinic DNA damage, and accumulation of platinum-DNA adducts in vitro.

Results: Oxaliplatin + cetuximab efficacy in murine subcutaneous xenograft models was greater than that of monotherapies and independent of the responsiveness to oxaliplatin monotherapy. In vitro, cetuximab reduced expression of excision repair cross-complementation group 1 and XPF, which are key components of the nucleotide excision repair pathway involved in the excision of platinum-DNA adducts. In addition, cetuximab reduced expression of XRCC1, a component of the base excision repair pathway responsible for the repair of apurinic/apyrimidinic sites. Effects of cetuximab on DNA repair protein levels were downstream to effects on mitogen-activated protein kinase and AKT pathway activation. In line with effects on DNA repair protein expression, cetuximab increased the accumulation of platinum and apurinic/apyrimidinic sites on DNA during oxaliplatin treatment.

Conclusions: Cetuximab has the potential to salvage the benefits of oxaliplatin in oxaliplatin-resistant colorectal cancer patients by reducing DNA repair capacity.
Src Continues Aging: Current and Future Clinical Directions
Authors: Kopetz Scott , Shah Ami N. , Gallick Gary E.
Published: December 2007

Aberrant activation of members of the Src family of nonreceptor protein tyrosine kinases is common in solid tumor malignancies and may contribute to the development and/or progression of these tumors. As a result, four Src inhibitors are now in more than 50 clinical trials for at least 14 different types of solid tumors. In this review, we briefly discuss the preclinical rationale for Src inhibitors, the development strategies most likely to be successful in the clinic, and the rationale for Src inhibitors in combination with other agents as part of a more comprehensive therapeutic strategy. As the use of Src family inhibitors in clinical trials on solid tumors is in its infancy, further studies on the roles of Src family kinases in tumor progression, chemoresistance, epidermal-to-mesenchymal transition, and other properties of tumor progression will be important in designing the most effective clinical trials using these inhibitors.
Mechanisms of Resistance to Histone Deacetylase Inhibitors and Their Therapeutic Implications
Authors: Fantin Valeria R. , Richon Victoria M.
Published: December 2007

Histone deacetylase inhibitors (HDI) are a promising new approach to the treatment of cancer. HDIs have been shown to induce differentiation, cell cycle arrest, and apoptosis in a variety of transformed cell lines; inhibit tumor growth in animal models; and show antitumor activity in clinical trials. Vorinostat, which has shown clinical responses in ∼30% of patients with advanced cutaneous T-cell lymphoma, is the first HDI approved for the treatment of cancer, and it is currently being evaluated in other indications. A better understanding of the molecular determinants of resistance to HDIs may provide the basis for therapeutic combinations with improved clinical efficacy. Poor response to treatment could be linked to systemic factors like pharmacokinetics or to tumor-specific factors both at the level of the malignant cells (tumor intrinsic) or the tumor microenvironment. This review focuses on the tumor intrinsic mechanisms of drug resistance (excluding mechanism of acquired resistance due to chronic exposure). In particular, attention is given to selected mechanisms that are relevant across chemical classes of HDIs and that can aid in the design of rational combination strategies.
Is Cell Death a Critical End Point for Anticancer Therapies or Is Cytostasis Sufficient?
Authors: Rixe Olivier , Fojo Tito
Published: December 2007

Since the discovery of conventional chemotherapy and the development of new target-based agents, the importance of cytostasis in anticancer activity has been debated. This review examines the relative importance of both cytostasis and cytotoxicity based on both preclinical data and clinical reports. Several limitations of our basic and clinical methods to evaluate cytostasis and cytotoxicity will be highlighted. Molecular mechanisms of cytostasis will be analyzed, including interference with the cell cycle as well as putative links with necrosis and autophagy. Finally, we will cite evidence that most older and newer compounds are both cytostatic and cytotoxic. The relative role of cytostasis and cytotoxicity on future drug screening and clinical development will be explored.
Relationship Clean-Up Time: Using Meta-Analysis and Path Analysis to Clarify Relationships Among Job Satisfaction, Perceived Fairness, and Citizenship Behaviors †
Authors: Fassina Neil E. , Jones David A. , Uggerslev Krista L.
Published: December 2007

Although perceived fairness and job satisfaction predict organizational citizenship behaviors (OCB), researchers have pondered the conceptual relationships among these constructs. Using path analysis on meta-analytically derived coefficients, the authors compared four models: full mediation (job satisfaction mediates fairness-OCB relationships), partial mediation, independent effects, and a spurious effects model (the job satisfaction—OCB relationship is spurious because perceived fairness is a common cause). The authors found greatest support for the independent effects model: Job satisfaction and different types of perceived fairness accounted for unique variance in OCB dimensions. The article discusses implications for research and practice, and offers suggestions to advance theory in this area.
The Moderating Effect of Work—Family Centrality on Work—Family Conflict, Organizational Attitudes, and Turnover Behavior†
Authors: Carr Jon C. , Boyar Scott L. , Gregory Brian T.
Published: December 2007

Research has explored the role of work—family conflict (WFC), including the antecedents and consequences of this construct. However, few studies have examined the specific role that work—family centrality plays in moderating the relationship between WFC and organizationally related outcomes. Using a sample of 129 employees from a manufacturing plant, we test the moderating influence of work—family centrality on the relationship between WFC and job satisfaction, organizational commitment, and retention. Results indicate that when individuals view work as being more central to their lives, the negative relationships between WFC and organizational attitudes and organizational retention is suppressed.
An Independent Bank of England
Authors: Patel Sucheen
Published: December 2007

This article traces the schemes for an independent Bank of England in the British political process in the late 1980s and early 1990s. The Treasury examined the issue of central bank independence on four separate occasions. Furthermore, the Bank of England held a series of internal discussions about its autonomy and about how such a reform could be implemented. Using recently released material disclosed under the 2000 Freedom of Information Act and interviews with former Treasury and Bank of England officials, these schemes are examined together with other corresponding discussions that pervaded the political process. It is shown that the debate surrounding an adjustment to the status of the Bank of England in terms of its structure and functions was embedded in the political and monetary institutions several years before the `sudden' implementation of the reform. Furthermore, the Labour Party's policy for central bank independence contained many features that originated in the preceding schemes.
Ethical Challenges for School Nurses in Documenting Schoolchildren's Health
Authors: Clausson Eva K. , Köhler Lennart , Berg Agneta
Published: December 2007

This study explored Swedish school nurses' experiences of school health record documentation. Fifty per cent of a representative sample of Swedish school nurses ( n = 129) reported difficulties with documenting mental and social health problems in family relationships, schoolchildren's behaviour, and school situations. Ethical considerations concerning fears of misinterpretation and practical barriers to documentation were expressed as reasons for their worries. Mental and social ill health is an increasing and often dominating problem among schoolchildren, thus proper documentation is a basic issue, both for individuals and for the population as a whole. School nurses obviously need professional guidance regarding documentation and ethical challenges. Systematic effort should be directed towards recognition and support of these nurses' unique opportunities to consider, follow and promote all aspects of schoolchildren's health.