bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the diagenetic evolution of potential reservoirs in fold/thrust belts: an example from eastern Venezuela
Authors: SCHNEIDER F. J. S.
Published: April 2010

Major oil discoveries in foothill areas have recently focused the interest of exploration companies sub-Andean basins. The SUBTRAP consortium was initiated in order to unravel the petroleum system associated with sub-thrust carbonate and sandstone reservoirs in various foreland fold-and-thrust belts around the world. As an illustration of the methodology defined by the consortium, this paper summarizes the main results of the integrated study using surface and subsurface geological data and basin modelling tools along a regional transect from eastern Venezuela. The focus of the study was to understand the porosity reduction and, therefore, the origin of the palaeofluids in the Upper Cretaceous–Oligocene sandstone reservoirs of the El Furrial structure (Venezuela). Basin modelling was performed using the
Thrustpack
,
Locace
and
Ceres
tools. The temperature and nature of the fluids obtained by this modelling were compared to fluid inclusions and oxygen isotope data on quartz overgrowths. Four observations were made.

From 65 Ma to 20 Ma fluids were at thermal equilibrium with the sediments. They were continuously expelled vertically toward the surface during compaction-driven de-watering processes.

From 20 Ma to 12 Ma, as a result of the regional tilting and the deposition of the synflexural Naricual Formation, the Cretaceous and Oligocene sandstones of the El Furrial structure became efficient conduits for fluids circulating from the north. These thrust-driven fluids (‘squeegee 1’) were at thermal equilibrium with the Cretaceous and Oligocene sandstones and seem to be correlated with the first generation of quartz overgrowths. This episode is characterized by an increase in the overpressure in the Oligocene and Upper Cretaceous sandstones correlated with a hydraulic fracturing of the sealing Carapita black shales.

From 12 Ma to 8 Ma fluids were expelled laterally from the Cretaceous sediments of the Pirital hanging-wall unit located immediately north of the El Furrial structure (‘squeegee 2’). These fluids were probably in chemical disequilibrium and their temperature was higher than the temperature of adjacent sediments. This probably resulted in additional, but minor, episodes of quartz precipitation. This hypothesis is consistent with the information obtained from oxygen isotope analyses, which suggest that subsequent generations of quartz cement probably formed from evolved basinal fluids.

At around 8 Ma a reduction in the intensity of the flow and then an inversion of this flow marked the sealing of the southern structural closure. Closure of the northern flank occurred at around 5Ma, as indicated by the present velocity of the fluids close to zero in the El Furrial reservoirs and the filling of the structure by hydrocarbons.
The drive for better bandwidth and resolution
Authors: EGAN M. S.
Published: April 2010

Bandwidth and resolution are attributes that are related yet distinct. Bandwidth refers to the breadth of frequencies comprising a spectrum. Resolution deals with resolving power – it is tied primarily to the highest frequency in the spectrum. Good bandwidth and good resolution are both useful in reservoir characterization. Understandably therefore, improving these attribute values has been a priority since the early days of the seismic method. Progress in that regard has been continuous. After a brief review of basic principles, this paper discusses some of the key, recent advances. They span acquisition, processing and interpretation disciplines.
Reducing structural uncertainties through anisotropic pre-stack depth imaging: examples from the Elgin/Franklin/Glenelg HP/HT fields area, Central North Sea
Authors: SUITER J. , ROMANI R. , ARNAUD J. , HOLLINGWORTH S. , HAWKINS K.
Published: April 2010

This paper highlights how a global approach to quantifying structural uncertainties has ultimately reduced overall structural uncertainty through improved seismic imaging, notably anisotropic pre-stack depth migration, in a structurally complex area. The Elgin/Franklin high pressure/high temperature (HP/HT) fields lie in the Central Graben area of the North Sea UK sector,
c
. 240 km east of Aberdeen. The fields are the deepest production in the North Sea and represent the largest gas condensate development in the world, with recoverable reserves estimated at over 700 × 10
6
BBL equivalent. The reservoirs produce from the Jurassic Fulmar shallow-marine and Pentland fluvial reservoirs at depths of 5100–5600 m subsea. Production from these HP/HT reservoirs (1100 bar/200°C) started in March 2001 and flows over 200 000 BOE per day from 12 wells.

For this type of producing environment, the stakes are high for understanding uncertainties related to imaging. Improved fault imaging translates not only to reduced uncertainties in bulk rock volumes, and ultimately in-place hydrocarbon volumes but also to an increased understanding of the static/dynamic behaviour of the fields through better imaging of internal faulting. The application of various proprietary and contractor-based seismic depth processing since 1997 has allowed for a better understanding of structural configuration of the deep reservoirs. This rich processing history has provided the interpretation team with various processing volumes (isotropic Post-SDM, anisotropic Post-SDM and, most recently, anisotropic Pre-SDM) to allow a more complete understanding of the uncertainties related to different imaging approaches.

Historically, the effects of anisotropy on vertical and lateral positioning were realized and a number of internal proprietary software tools were developed to quality control depth imaging processing. The 1998 Glenelg discovery southwest of Elgin Field was the focus for the initial anisotropic Pre-SDM study, which was later expanded to include the Elgin/Franklin fields area. This processing benefited from Total’s internal QC tools and a combination of additional data (e.g. walk-away VSP profiles with different orientations, long-offset 2D seismic data) which provided an optimum mix to derive and verify the anisotropic parameters for the velocity model. Overall, the new seismic data shown significant improvement over the previous time- and depth-migrated datasets, reduced uncertainty on internal and bounding-fault positions and allowed the observation of the vertical and spatial uncertainties attached to different migration approaches. This understanding of the variability in seismic imaging and its effects on the reservoir parameters and structural configurations in depth is used as an input to understand ranges of in-place hydrocarbon volumes, the potential of near-field exploration and future infill-drilling strategies.
Preliminary results from investigations of seismic and petrophysical properties of Faroes basalts in the SeiFaBa project
Authors: JAPSEN P. , ANDERSEN C. , ANDERSEN H. L. , ANDERSEN M. S. , BOLDREEL L. O. , MAVKO G. , MOHAMMED N. G. , PEDERSEN J. M. , PETERSEN U. K. , RASMUSSEN R. , SHAW F. , SPRINGER N. , WAAGSTEIN R. , WHITE R. S. , WORTHINGTON M.
Published: April 2010

The development of methods of seismic imaging beneath basalts is still hindered by a lack of knowledge about the elastic properties of basaltic sequences and the degree of three-dimensional heterogeneity. The SeiFaBa project (2002–2005) is funded by the Sindri Group as part of the programmes for licensees within the Faroese area and will attempt to address these issues.

The Glyvursnes-1 well was drilled by SeiFaBa through the Upper Basalt Formation outside Tórshavn in 2002. A full core and numerous wireline logs were acquired from the 700m deep well. During the same operations, the existing 660m deep Vestmanna-1 well drilled mainly into the Middle Basalt Formation was reamed and logged. The two wells are central to a number of closely co-ordinated experiments, which are all targeted at creating models for seismic wave propagation through a succession of basalt by combining detailed analysis at core, log and seismic scales. Data from these two wells, in combination with the data for the Lopra-1 well drilled into the Lower Basalt Formation, will give new stratigraphic and petrophysical control of the Lower, Middle and Upper Basalt formations on the Faroes.

The seismic programme was initiated in 2002 and the main acquisition was carried out during 2003. The well site at Glyvursnes gives optimal conditions for combining VSP, offset-VSP and surface seismic experiments both onshore and offshore and the seismic effects of a nearby near-vertical shear zone can be studied in detail. Preliminary analysis of log data from the Lopra-1 well suggests that the acoustic properties of these basalt flows are mainly controlled by porosity of a stiff matrix filled with clay minerals and water. Further studies will allow for explanations of the sonic response of basalt in terms of physical and compositional properties and a better understanding of the seismic signatures of flood basalt successions.
Three-dimensional visualization for well placement and geosteering: Njord Field, offshore mid-Norway
Authors: DART C. , DENICHOU J. M. , BRIDGER T. , HAUGEN R. , SJØHOLM J. , HALVORSEN Å. , ØYE V. , SEIM M.
Published: April 2010

Njord is a structurally complex Lower Jurassic oil field located on the Halten Terrace, offshore mid-Norway. The field was discovered in 1986 and has been under production since 1997. The field is produced by a combination of depletion and crestal gas injection. Difficulties in finding new economically viable drilling targets led to a drilling stop in 2001–2002 and production is now in decline. A second drilling phase comprising three infill wells began in late 2002. Production results from these three wells will be critical for determining Njord’s future beyond 2005. During the drilling stop, advanced 3D visualization techniques were used to unravel the field’s complex extensional fault pattern. New well targets were identified using multiple seismic datasets and multiple interpretations. 3D visualization was also used during drilling to keep the wells within the reservoir and to avoid an unstable formation.

Reservoir simulation models were used to identify areas with undrained potential, and 4D seismic data indicated fault blocks where changes in gas saturation had occurred. The reservoir oil is initially under-saturated, but gas has also come out of solution in areas with significant pressure depletion. Gas has also been re-injected. New wells were planned to avoid these fault blocks. Target points were placed using 3D visualization software and well path dog-leg angles were calculated. The process continued iteratively until a well path had been achieved with maximum reservoir penetration and realistic dog-leg angles (< 3.5°). Real time data were transmitted to shore during drilling using a web service. These data included survey, petrophysical log, biostratigraphical and borehole image data that were used alongside the 3D visualizations. In this way, drilling progress through the G&G interpretation was continuously monitored. Similarly, geosteering, or plug back and sidetrack, decisions were quickly evaluated.

Supplementary material:
Movies referred to in the article are available at
https://doi.org/10.6084/m9.figshare.c.4812936
The MacCulloch Field: improving reservoir characterization through time-lapse analysis
Authors: SCORER J. , FULLER N. , MALCOLM J. , BRUNER J.
Published: April 2010

The MacCulloch oil field lies in Block 15/24b in the UK Central North Sea. The field is produced using a floating production storage and offtake facility from two sub-sea centres and has been on production since 1997.

The original geophysical mapping of the field was based on 3D seismic data acquired in 1993. In April 2002, a repeat 3D survey was acquired over the field with the aim of better understanding the depletion of the field using time-lapse seismic analysis.

The MacCulloch Field reservoirs are turbidites of the Upper Balmoral Sandstone Unit in the Lista Formation of the Upper Paleocene, which are connected to a large aquifer in the underlying Lower Balmoral Sandstone Unit. Connection to such a large aquifer means that pressure support over field life has been very good (<100 psi drop over field life). This fact, coupled with the lack of a gas cap, means that for the time-lapse analysis any change should primarily be due to a substitution of water for oil.

The MacCulloch Field reservoir is made up of five discrete turbidite sandstone-dominated sand bodies, which can be distinguished on the seismic data. Examination of the time-lapse response in these bodies shows that they have acted as a primary control on the depletion of the field. The individual bodies have been analysed using 3D visualization and interpretation techniques, and incorporated into the geological model with differing rock properties assigned to each. Within the reservoir simulation model, the assignment of directional permeabilities to these units and the placing of transmissibility barriers at their boundaries substantially improved the history match of the field, thereby enhancing our ability to predict future performance and identify possible infill drilling locations.
Application of 3D seismic visualization techniques for seismic stratigraphy, seismic geomorphology and depositional systems analysis: examples from fluvial to deep-marine depositional environments
Authors: POSAMENTIER H. W.
Published: April 2010

In recent years, 3D seismic has become an essential tool for the interpretation of subsurface stratigraphy and depositional systems. Seismic stratigraphy in conjunction with seismic geomorphology, calibrated by borehole data, has elevated the degree to which seismic data can facilitate geological interpretation. 3D seismic data has enabled interpreters to visualize details of complex depositional systems, which can be incorporated into borehole planning for exploration as well as development needs to improve risk management significantly. Common techniques for geological visualization include (1) imaging stratigraphic horizons, (2) time slicing and flattened time slicing, (3) interval attribute analysis, (4) voxbody interpretation and mapping, (5) 3D perspective rendering and (6) opacity rendering.

One of the key benefits of modern 3D seismic interpretation is that stratigraphic horizons can be interpreted and horizon attributes (such as reflection amplitude, dip magnitude, dip azimuth, and curvature) can then be imaged directly in 2D or 3D space. Techniques such as variable illumination can enhance geomorphological interpretations, and, when integrated with stratigraphic analyses, can yield insights regarding distribution of source, seal, and reservoir facies. Stratigraphic intervals bracketing sections of geological interest can be evaluated for amplitude and frequency content and can contribute to geological interpretations. Time slices and flattened time slices (also referred to as horizon slices) can bring to light map patterns and geological features that other techniques might overlook. Voxel picking can further bring out features of geological interest. This method involves auto-picking of connected voxels of similar seismic character, a technique that can illuminate discrete depositional elements in three dimensions. Similarly, opacity rendering, which makes opaque only those voxels that lie within a certain range of seismic values, can further bring out features of stratigraphic interest. Examples of fluvial, shallow marine, and deep marine depositional environments are shown. A variety of visualization techniques are applied to these examples in an effort to illustrate the variety of interpretation techniques available to the geoscientist. These examples will highlight the integration of seismic stratigraphic and seismic geomorphological analyses essential for maximum benefit to be derived from geological analyses of 3D seismic data.
Kilometre-scale sandstone intrusions in the Eocene of the Outer Moray Firth (UK North Sea): migration paths, reservoirs and potential drilling hazards
Authors: HUUSE M. , CARTWRIGHT J. A. , GRAS R. , HURST A.
Published: April 2010

Kilometre-scale sandstone intrusions have recently been documented from the Palaeogene deep-water sequences of the northern North Sea. The distribution of Eocene sandstones within a 126 km
2
3D4C seismic survey located in the Outer Moray Firth was mapped using surface and volume based interpretation of converted wave seismic data calibrated to a number of boreholes. About 35 conical sandstone intrusions, a few tens of metres thick and 1–1.5 km wide, were mapped within the lower Eocene. The intrusions are inclined about 15–20° and crosscut some 100–200 m of lower Eocene mudstones, terminating upward at the Middle Eocene unconformity, below the oil-charged, upper Eocene sandstones of the Alba and Chestnut reservoirs. Individual sandstone intrusions may contain millions of cubic metres of sandstone and often have excellent reservoir properties. Previous studies failed to define a viable migration path for the oil in the Alba/Chestnut reservoirs because they appeared to be completely encased in poorly permeable Eocene mudstones. However, detailed mapping and volume visualization of the converted wave seismic data demonstrates that the upper Eocene reservoirs have suffered post-depositional remobilization and that the conical intrusions provide a viable migration path between the Alba/Chestnut reservoirs and the underlying Paleocene aquifers. Despite more than two decades of exploration activity in the Outer Moray Firth, the widespread occurrence of conical intrusions in the lower Eocene is still not widely recognized, and it is likely that the sandstones may pose a hazard when drilling for deeper targets. However, it is also possible that large conical intrusions that do not connect with overlying sandstones may contain economical quantities of hydrocarbons.

Supplementary material:
The movie referred to in the article is available at
https://doi.org/10.6084/m9.figshare.c.4812948
Automated mapping of carbonate build-ups and palaeokarst from the Norwegian Barents Sea using 3D seismic texture attributes
Authors: CARRILLAT A. , HUNT D. , RANDEN T. , SONNELAND L. , ELVEBAKK G.
Published: April 2010

Geological heterogeneity in hydrocarbon reservoirs is normally related to variability in depositional facies, diagenesis and structure. On the Loppa High, Norwegian Barents Sea, reservoir quality in prospective Upper Palaeozoic carbonates is considered to be controlled mainly by primary depositional facies variability linked to active faulting, with a secondary overprint of palaeokarst. The best quality reservoirs are anticipated in build-up facies. Although high-quality 3Dseismic data exist over the prospect, it is a challenge to map the buildups and palaeokarst in three-dimensional space using conventional 3Dseismic interpretation tools. This is mainly due to the internal heterogeneity of the build-ups and palaeokarst, which are characterized by a range of seismic reflection/attribute patterns.

A procedure for multi-attribute mapping of seismic facies is described and utilized to provide a truly threedimensional interpretation of build-up and palaeokarst geobodies. A neural network classifier is used to analyse a set of 3D attributes that capture the seismic stratigraphical and structural patterns inherent in the data. These attributes are referred to as 3D texture attributes since they describe the reflector-geometry in a small 3D neighbourhood. Pattern recognition is interpreter-guided, with the desired seismic facies to be mapped input as ‘training data’ and analysed prior to their presentation to the 3D-classification system. Once the classification is made, the interpreter is presented with a 3D classified volume and an uncertainty analysis of each of the mapped facies/classes. This is used to evaluate the results prior to their visualization in 3D space. The method allows the interpreter to identify quickly a volume where the features of interest occur and to focus the interpretation work directly on them. In addition, the 3D visualization of the mapped geobodies brings important new information that might be overlooked when inspecting data in vertical or horizontal data windows.

In the Norwegian Barents Sea case study, 3Dseismic facies mapping provides the first truly three-dimensional interpretation of the build-ups and palaeokarst, where their external form, juxtaposition, cross-cutting relationships and structural information are preserved. These data give new insights as to the stratigraphic distribution and internal variability of the build-ups and palaeokarst system; this information is important to estimation of reservoir volume, connectivity and variability.
Salt tectonics above complex basement extensional fault systems: results from analogue modelling
Authors: DOOLEY T. , McCLAY K. R. , HEMPTON M. , SMIT D.
Published: April 2010

Physical model studies of salt tectonics related to thick-skinned extension have been largely confined to 2Dstructures. An experimental programme, utilizing silicone polymer and silica sand/ceramic beads as ductile and brittle analogues respectively, was designed to investigate the 3D relationships between salt diapirs and intersecting basement fault systems seen in the Central Graben, UK North Sea.

During extension, intersection points in the basement fault system generate complex single, two-way or three-way, flap structures in the overburden, localizing deformation and footwall diapiric activity on the rift margins. Flap structures and associated diapirs are located adjacent to, but diagonally inboard of, the basement intersection points and consist of single, or multiple, convex-to-the-hanging-wall fault segments that are gradually breached with increasing extension. Major diapirs that attain passive status accommodate much of the continued basement extension through down building processes. Intra-basin horst systems develop inwardly dipping graben, cored by a major salt wall, during initial extension. Axial flow along this structure feeds growing diapirs. Grounding of the brittle overburden results in source cut-off and deflation of the salt wall due to continued expansion by extensional faulting.

During subsequent inversion major diapirs are reactivated, exhibiting rapid active rise through the overburden, suggesting that buoyancy forces associated with diapirs play a major role in their reaction to subsequent tectonic stresses. Basin margins with major corner point systems develop highly segmented inversion fronts related to the localized nature of brittle structuring during extension. Diapir crests and entrained salt bodies are nucleation sites for the development of brittle reverse faults. Basin margins with minor corner systems commonly demonstrate reactivation of the basin margin fault system, producing a linked inversion front. The models display close similarities to structures seen in the UK Central North Sea and other salt basins, and have important implications for basement control on diapir locations during post-salt basin extension.
Thermoregulatory, behavioral, and metabolic responses to heatstroke in a conscious mouse model
Authors: Leon Lisa R. , Gordon Christopher J. , Helwig Bryan G. , Rufolo Dennis M. , Blaha Michael D.
Published: April 2010

The typical core temperature (Tc) profile displayed during heatstroke (HS) recovery consists of initial hypothermia followed by delayed hyperthermia. Anecdotal observations led to the conclusion that these Tc responses represent thermoregulatory dysfunction as a result of brain damage. We hypothesized that these Tc responses are mediated by a change in the temperature setpoint. Tc (± 0.1°C; radiotelemetry) of male C57BL/6J mice was monitored while they were housed in a temperature gradient with ambient temperature (Ta) range of 20–39°C to monitor behaviorally selected Ta (Ts) or an indirect calorimeter (Ta = 25°C) to monitor metabolism (V̇o2) and calculate respiratory exchange ratio (RER). Responses to mild and severe HS (thermal area 249.6 ± 18.9 vs. 299.4 ± 19.3°C·min, respectively) were examined through 48 h of recovery. An initial hypothermia following mild HS was associated with warm Ts (∼32°C), ∼35% V̇o2 decrease, and RER ∼0.71 that indicated reliance on fatty acid oxidation. After 24 h, mild HS mice developed hyperthermia associated with warm Ts (∼32°C), ∼20% V̇o2 increase, and RER ∼0.85. Severe HS mice appeared poikilothermic-like in the temperature gradient with Tc similar to Ts (∼20°C), and these mice failed to recover from hypothermia and develop delayed hyperthermia. Cellular damage (hematoxylin and eosin staining) was undetectable in the hypothalamus or other brain regions in severe HS mice. Overall, decreases and increases in Tc were associated with behavioral and autonomic thermoeffectors that suggest HS elicits anapyrexia and fever, respectively. Taken together, Tc responses of mild and severe HS mice suggest a need for reinterpretation of the mechanisms of thermoregulatory control during recovery.
Impact of elevated dietary sodium intake on NAD(P)H oxidase and SOD in the cortex and medulla of the rat kidney
Authors: Johns Edward J. , O'Shaughnessy Barbara , O'Neill Susan , Lane Bríd , Healy Vincent
Published: April 2010

Pathophysiological states, including cardiovascular and renal diseases, are characterized by oxidative stress but what is less clear is whether physiological challenges incur a degree of altered oxidative metabolism. To this end, this study examined whether exposure to a high dietary sodium intake could cause an oxidative stress at the kidney. Animals, placed on either 0.3% or 3% sodium diets for 2 wk, were given a lethal dose of anesthetic, and kidneys were removed to analyze both NAD(P)H oxidase (NOX) and superoxide dismutase (SOD) expression and activities in the cortex and medulla. Placing animals on the high-sodium diet raised sodium and water excretion and caused an ∼14-fold increase in urinary excretion of 8-isoprostane, a marker of oxidative stress, which was attenuated by chronic treatment with apocynin to prevent NAD(P)H oxidase activity. The protein expression of the NAD(P)H oxidase subunits NOX2 and p47phox and overall NAD(P)H oxidase activity were approximately doubled in the cortex of the rats on the high-sodium diet compared with those on the normal sodium intake while both SOD activity and expression were unchanged. By contrast, neither NOX nor SOD protein expression or activity were altered in the medulla when the rats were placed on the high-sodium intake. These data suggest that an elevation in dietary sodium intake can lead to increased generation of reactive oxygen species and a state of oxidative stress in the cortex but not to such a degree that it extends to the medulla.
Multiple Manifestations of Microstimulation in the Optic Tectum: Eye Movements, Pupil Dilations, and Sensory Priming
Authors: Netser Shai , Ohayon Shay , Gutfreund Yoram
Published: April 2010

It is well established that the optic tectum (or its mammalian homologue, the superior colliculus) is involved in directing gaze toward salient stimuli. However, salient stimuli typically induce orienting responses beyond gaze shifts. The role of the optic tectum in generating responses such as pupil dilation, galvanic responses, or covert shifts is not clear. In the present work, we studied the effects of microstimulation in the optic tectum of the barn owl ( Tyto alba) on pupil diameter and on eye shifts. Experiments were conducted in lightly anesthetized head-restrained barn owls. We report that low-level microstimulation in the deep layers of the optic tectum readily induced pupil dilation responses (PDRs), as well as small eye movements. Electrically evoked PDRs, similar to acoustically evoked PDRs, were long-lasting and habituated to repeated stimuli. We further show that microstimulation in the external nucleus of the inferior colliculus also induced PDRs. Finally, in experiments in which tectal microstimulations were coupled with acoustic stimuli, we show a tendency of the microstimulation to enhance pupil responses and eye shifts to previously habituated acoustic stimuli. The enhancement was dependent on the site of stimulation in the tectal spatial map; responses to sounds with spatial cues that matched the site of stimulation were more enhanced compared with sounds with spatial cues that did not match. These results suggest that the optic tectum is directly involved in autonomic orienting reflexes as well as in gaze shifts, highlighting the central role of the optic tectum in mediating the body responses to salient stimuli.
Pathogenic peptide deviations support a model of adaptive evolution of chordate cardiac performance by troponin mutations
Authors: Palpant Nathan J. , Houang Evelyne M. , Delport Wayne , Hastings Kenneth E. M. , Onufriev Alexey V. , Sham Yuk Y. , Metzger Joseph M.
Published: April 2010

In cardiac muscle, the troponin (cTn) complex is a key regulator of myofilament calcium sensitivity because it serves as a molecular switch required for translating myocyte calcium fluxes into sarcomeric contraction and relaxation. Studies of several species suggest that ectotherm chordates have myofilaments with heightened calcium responsiveness. However, genetic polymorphisms in cTn that cause increased myofilament sensitivity to activating calcium in mammals result in cardiac disease including arrhythmias, diastolic dysfunction, and increased susceptibility to sudden cardiac death. We hypothesized that specific residue modifications in the regulatory arm of troponin I (TnI) were critical in mediating the observed decrease in myofilament calcium sensitivity within the mammalian taxa. We performed large-scale phylogenetic analysis, atomic resolution molecular dynamics simulations and modeling, and computational alanine scanning. This study provides evidence that a His to Ala substitution within mammalian cardiac TnI (cTnI) reduced the thermodynamic potential at the interface between cTnI and cardiac TnC (cTnC) in the calcium-saturated state by disrupting a strong intermolecular electrostatic interaction. This key residue modification reduced myofilament calcium sensitivity by making cTnI molecularly untethered from cTnC. To meet the requirements for refined mammalian adult cardiac performance, we propose that compensatory evolutionary pressures favored mutations that enhanced the relaxation properties of cTn by decreasing its sensitivity to activating calcium.
Identifying Functional Mechanisms of Gene and Protein Regulatory Networks in Response to a Broader Range of Environmental Stresses
Authors: Li Cheng-Wei , Chen Bor-Sen
Published: April 2010

Cellular responses to sudden environmental stresses or physiological changes provide living organisms with the opportunity for final survival and further development. Therefore, it is an important topic to understand protective mechanisms against environmental stresses from the viewpoint of gene and protein networks. We propose two coupled nonlinear stochastic dynamic models to reconstruct stress-activated gene and protein regulatory networks via microarray data in response to environmental stresses. According to the reconstructed gene/protein networks, some possible mutual interactions, feedforward and feedback loops are found for accelerating response and filtering noises in these signaling pathways. A bow-tie core network is also identified to coordinate mutual interactions and feedforward loops, feedback inhibitions, feedback activations, and cross talks to cope efficiently with a broader range of environmental stresses with limited proteins and pathways.
Ulvan, a Sulfated Polysaccharide from Green Algae, Activates Plant Immunity through the Jasmonic Acid Signaling Pathway
Authors: Jaulneau Valérie , Lafitte Claude , Jacquet Christophe , Fournier Sylvie , Salamagne Sylvie , Briand Xavier , Esquerré-Tugayé Marie-Thérèse , Dumas Bernard
Published: April 2010

The industrial use of elicitors as alternative tools for disease control needs the identification of abundant sources of them. We report on an elicitor obtained from the green algaeUlvaspp. A fraction containing most exclusively the sulfated polysaccharide known as ulvan-induced expression of a GUS gene placed under the control of a lipoxygenase gene promoter. Gene expression profiling was performed upon ulvan treatments onMedicago truncatulaand compared to phytohormone effects. Ulvan induced a gene expression signature similar to that observed upon methyl jasmonate treatment (MeJA). Involvement of jasmonic acid (JA) in ulvan response was confirmed by detecting induction of protease inhibitory activity and by hormonal profiling of JA, salicylic acid (SA) and abscisic acid (ABA). Ulvan activity on the hormonal pathway was further consolidated by usingArabidopsishormonal mutants. Altogether, our results demonstrate that green algae are a potential reservoir of ulvan elicitor which acts through the JA pathway.
Multi‐FPGA Partitioning Method Based on Topological Levelization
Authors: Kerkiz Nabil , Elchouemi Amr , Bouldin Don
Published: April 2010

This paper presents a partitioning method based on topological ordering and levelization. The proposed method, termed RPL, performs multi‐FPGA partitioning by taking into account six different partitioning constraints. We also compare RPL to two existing algorithms. The first approach is a hierarchical partitioning method based on topological ordering (HP). The second approach is a recursive algorithm based on the Fiduccia and Mattheyses bipartitioning heuristic (RP). Experimental results on seven application benchmarks mapped onto three different hardware architectures demonstrated that the proposed RPL approach achieved fewer partitions in less time when compared to the RP and HP algorithms.
Vital Pulp Therapy—Current Progress of Dental Pulp Regeneration and Revascularization
Authors: Zhang Weibo , Yelick Pamela C.
Published: April 2010

Pulp vitality is extremely important for the tooth viability, since it provides nutrition and acts as biosensor to detect pathogenic stimuli. In the dental clinic, most dental pulp infections are irreversible due to its anatomical position and organization. It is difficult for the body to eliminate the infection, which subsequently persists and worsens. The widely used strategy currently in the clinic is to partly or fully remove the contaminated pulp tissue, and fill and seal the void space with synthetic material. Over time, the pulpless tooth, now lacking proper blood supply and nervous system, becomes more vulnerable to injury. Recently, potential for successful pulp regeneration and revascularization therapies is increasing due to accumulated knowledge of stem cells, especially dental pulp stem cells. This paper will review current progress and feasible strategies for dental pulp regeneration and revascularization.
On Regular Elements in an Incline
Authors: Meenakshi A. R. , Anbalagan S.
Published: April 2010

Inclines are additively idempotent semirings in which products are less than (or) equal to either factor. Necessary and sufficient conditions for an element in an incline to be regular are obtained. It is proved that every regular incline is a distributive lattice. The existence of the Moore‐Penrose inverse of an element in an incline with involution is discussed. Characterizations of the set of all generalized inverses are presented as a generalization and development of regular elements in a ∗‐regular ring.
Demineralization Depth Using QLF and a Novel Image Processing Software
Authors: Wu Jun , Donly Zachary R. , Donly Kevin J. , Hackmyer Steven
Published: April 2010

Quantitative Light-Induced fluorescence (QLF) has been widely used to detect tooth demineralization indicated by fluorescence loss with respect to surrounding sound enamel. The correlation between fluorescence loss and demineralization depth is not fully understood. The purpose of this project was to study this correlation to estimate demineralization depth. Extracted teeth were collected. Artificial caries-like lesions were created and imaged with QLF. Novel image processing software was developed to measure the largest percent of fluorescence loss in the region of interest. All teeth were then sectioned and imaged by polarized light microscopy. The largest depth of demineralization was measured by NIH ImageJ software. The statistical linear regression method was applied to analyze these data. The linear regression model wasY=0.32X+0.17, whereXwas the percent loss of fluorescence andYwas the depth of demineralization. The correlation coefficient was 0.9696. The two-tailed t-test for coefficient was 7.93, indicating theP-value=.0014. TheFtest for the entire model was 62.86, which shows theP-value=.0013. The results indicated statistically significant linear correlation between the percent loss of fluorescence and depth of the enamel demineralization.
Transcriptional Repression of SKP2 Is Impaired in MYCN-Amplified Neuroblastoma
Authors: Muth Daniel , Ghazaryan Seda , Eckerle Isabella , Beckett Emily , Pöhler Christina , Batzler Julia , Beisel Claudia , Gogolin Sina , Fischer Matthias , Henrich Kai-Oliver , Ehemann Volker , Gillespie Paul , Schwab Manfred , Westermann Frank
Published: April 2010

The cell cycle regulator, SKP2, is overexpressed in various cancers and plays a key role in p27 degradation, which is involved in tumor cell dedifferentiation. Little is known about the mechanisms leading to impaired SKP2 transcriptional control in tumor cells. We used neuroblastoma as a model to study SKP2 regulation because SKP2 transcript levels gradually increase with aggressiveness of neuroblastoma subtypes. The highest SKP2 levels are found in neuroblastomas with amplified MYCN. Accordingly, we found 5.5-fold (range, 2–9.5) higher SKP2 core promoter activity in MYCN-amplified cells. Higher SKP2 core promoter activity in MYCN-amplified cells is mediated through a defined region at the transcriptional start site. This region includes a specific E2F-binding site that makes SKP2 activation largely independent of mitogenic signals integrated through the SP1/ELK-1 site. We show by chromatin immunoprecipitation that SKP2 activation through the transcriptional start site in MYCN-amplified cells is associated with the low abundance of pRB-E2F1 complexes bound to the SKP2 promoter. Transcriptional control of SKP2 through this regulatory mechanism can be reestablished in MYCN-amplified cells by restoring pRB activity using selective small compound inhibitors of CDK4. In contrast, doxorubicin or nutlin-3 treatment—both leading to p53-p21 activation—or CDK2 inhibition had no effect on SKP2 regulation in MYCN-amplified cells. Together, this implies that deregulated MYCN protein levels in MYCN-amplified neuroblastoma cells activate SKP2 through CDK4 induction, abrogating repressive pRB-E2F1 complexes bound to the SKP2 promoter. Cancer Res; 70(9); 3791–802. ©2010 AACR.
Disulfiram Treatment Facilitates Phosphoinositide 3-Kinase Inhibition in Human Breast Cancer Cells In vitro and In vivo
Authors: Zhang Haijun , Chen Di , Ringler Jonathan , Chen Wei , Cui Qiuzhi Cindy , Ethier Stephen P. , Dou Q. Ping , Wu Guojun
Published: April 2010

Frequent genetic alterations of the components in the phosphoinositide 3-kinase (PI3K)/PTEN/AKT signaling pathway contribute greatly to breast cancer initiation and progression, which makes targeting this signaling pathway a promising therapeutic strategy for breast cancer treatment. In this study, we showed that in the presence of copper (Cu), disulfiram (DSF), a clinically used antialcoholism drug, could potently inhibit breast cancer cell growth regardless of the PIK3CA status. Surprisingly, the treatment with a mixture of DSF and copper (DSF-Cu) led to the decreased expression of PTEN protein and the activation of AKT in a dose- and time-dependent manner in different cell lines with or without PIK3CA mutations. Treatment of breast cancer cell lines with a combination of DSF-Cu and LY294002, a pan-PI3K inhibitor, resulted in the significant inhibition of cell growth when compared with either drug alone. In addition, the combined treatment of DSF and LY294002 significantly inhibited the growth of the breast tumor xenograft in nude mice induced by MDA-MB-231 cells expressing mutant PIK3CA-H1047R and PIK3CA-E545K, whereas neither DSF nor LY294002 alone could significantly retard tumor growth. Finally, the observed in vivo inhibitory effects are found associated with aberrant signaling alterations and apoptosis-inducing activities in tumor samples. Thus, our finding shows for the first time that treatment of breast cancer with DSF results in a novel feedback mechanism that activates AKT signaling. Our study also suggests that the combination of DSF and a PI3K inhibitor may offer a new combinational treatment model for breast cancer, particularly for those with PIK3CA mutations. Cancer Res; 70(10); 3996–4004. ©2010 AACR.
Activation of NF-κB Signaling by Inhibitor of NF-κB Kinase β Increases Aggressiveness of Ovarian Cancer
Authors: Hernandez Lídia , Hsu Sarah C. , Davidson Ben , Birrer Michael J. , Kohn Elise C. , Annunziata Christina M.
Published: April 2010

The NF-κB family of transcription factors has been implicated in the propagation of ovarian cancer, but the significance of constitutive NF-κB signaling in ovarian cancer is unknown. We hypothesized that constitutive NF-κB signaling defines a subset of ovarian cancer susceptible to therapeutic targeting of this pathway. We investigated the biological relevance of NF-κB in ovarian cancer using a small-molecule inhibitor of inhibitor of NF-κB kinase β (IKKβ) and confirmed with RNA interference toward IKKβ. We developed a gene expression signature of IKKβ signaling in ovarian cancer using both pharmacologic and genetic manipulation of IKKβ. The expression of IKKβ protein itself and the nine-gene ovarian cancer–specific IKKβ signature were related to poor outcome in independently collected sets of primary ovarian cancers (P = 0.02). IKKβ signaling in ovarian cancer regulated the transcription of genes involved in a wide range of cellular effects known to increase the aggressive nature of the cells. We functionally validated the effect of IKKβ signaling on proliferation, invasion, and adhesion. Downregulating IKKβ activity, either by a small-molecule kinase inhibitor or by short hairpin RNA depletion of IKKβ, blocked all of these cellular functions, reflecting the negative regulation of the target genes identified. The diversity of functions controlled by IKKβ in ovarian cancer suggests that therapeutic blockade of this pathway could be efficacious if specific IKKβ inhibitor therapy is focused to patients whose tumors express a molecular profile suggestive of dependence on IKKβ activity. Cancer Res; 70(10); 4005–14. ©2010 AACR.
Selective Autophagy in Cancer Development and Therapy
Authors: Dikic Ivan , Johansen Terje , Kirkin Vladimir
Published: April 2010

Like other cells in the body, tumor cells depend on the evolutionarily conserved autophagy pathway to survive starvation and stress. Simultaneously, autophagy represents an important tumor-suppressive mechanism. Recent studies have shed new light on this apparent discrepancy and revealed mechanisms by which autophagy can modulate different stages of cancer development. The molecular basis of selectivity in autophagy employs specific receptor molecules, such as p62/SQSTM1, which are able to link autophagy targets and autophagosomal membranes. We discuss the emerging principles of selective autophagy in cancer pathogenesis and treatment. Cancer Res; 70(9); 3431–4. ©2010 AACR.
Distinct Biological Roles for the Akt Family in Mammary Tumor Progression
Authors: Dillon Rachelle L. , Muller William J.
Published: April 2010

The phosphatidylinositol 3′ kinase/Akt pathway is frequently dysregulated in cancer, which can have unfavorable consequences in terms of cell proliferation, survival, metabolism, and migration. Increasing evidence suggests that Akt1, Akt2, and Akt3 play unique roles in breast cancer initiation and progression. We have recently shown that in contrast to Akt1, which accelerates mammary tumor induction in transgenic mice, Akt2 promotes metastasis of tumor cells without affecting the latency of tumor development. Despite the distinct phenotypic outputs resulting from Akt1 or Akt2 activation, very little is known about the mode by which such unique functions originate from these highly related kinases. Here we discuss potential mechanisms contributing to the differing functional specificity of Akt1 and Akt2 with respect to migration, invasion, and metastasis. Cancer Res; 70(11); 4260–4. ©2010 AACR.
Aurora Kinase A Promotes Ovarian Tumorigenesis through Dysregulation of the Cell Cycle and Suppression of BRCA2
Authors: Yang Gong , Chang Bin , Yang Fan , Guo Xiaoqing , Cai Kathy Qi , Xiao Xue (Sherry) , Wang Huamin , Sen Subrata , Hung Mien-Chie , Mills Gordon B. , Chang Sandy , Multani Asha S. , Mercado-Uribe Imelda , Liu Jinsong
Published: April 2010

Purpose: Aurora kinase A (Aurora-A) is known to regulate genomic instability and tumorigenesis in multiple human cancers. The underlying mechanism, however, is not fully understood. We examined the molecular mechanism of Aurora-A regulation in human ovarian cancer.

Experimental Design: Retrovirus-mediated small hairpin RNA (shRNA) was used to silence the expression of Aurora-A in the ovarian cancer cell lines SKOV3, OVCA432, and OVCA433. Immunofluorescence, Western blotting, flow cytometry, cytogenetic analysis, and animal assay were used to test centrosome amplification, cell cycle alteration, apoptosis, DNA damage response, tumor growth, and genomic instability. Immunostaining of BRCA2 and Aurora-A was done in ovarian, pancreatic, breast, and colon cancer samples.

Results: Knockdown of Aurora-A reduced centrosome amplification, malformation of mitotic spindles, and chromosome aberration, leading to decreased tumor growth. Silencing Aurora-A attenuated cell cycle progression and enhanced apoptosis and DNA damage response by restoring p21, pRb, and BRCA2 expression. Aurora-A was inversely correlated with BRCA2 in high-grade ovarian serous carcinoma, breast cancer, and pancreatic cancer. In high-grade ovarian serous carcinoma, positive expression of BRCA2 predicted increased overall and disease-free survival, whereas positive expression of Aurora-A predicted poor overall and disease-free survival (P < 0.05). Moreover, an increased Aurora-A to BRCA2 expression ratio predicted poor overall survival (P = 0.047) compared with a decreased Aurora-A to BRCA2 expression ratio.

Conclusion: Aurora-A regulates genomic instability and tumorigenesis through cell cycle dysregulation and BRCA2 suppression. The negative correlation between Aurora-A and BRCA2 exists in multiple cancers, whereas the expression ratio of Aurora-A to BRCA2 predicts ovarian cancer patient outcome. Clin Cancer Res; 16(12); 3171–81. ©2010 AACR.