bluuebunny/crossref_metadata_2025 huggingface dataset:
STRATEGIC AND OPERATIVE LEVEL FRONT-END INNOVATION ACTIVITIES — INTEGRATION PERSPECTIVE
Authors: POSKELA JARNO
Published: September 2007

The front-end phase is in the literature generally regarded as the most critical phase of the innovation process. Front-end management has a strategic nature since important decisions related e.g. to target markets and the main functionalities of products are done in the front-end phase. This article examines how the integration of strategic and operative level front-end activities is perceived by top managers in the product innovation context. The findings indicate that companies exploit different strategy-making processes, and that each strategy-making mode is prone to particular integration challenges. The results show that the effectiveness of integration of strategic and operative level front-end activities is dependent on the level of concreteness of the defined business strategies, the amount of business-minded decision making, and the balance between control and creativity.
A review of recent Phanerozoic time-scales
Authors: Snelling N. J.
Published: September 2007

The development of the K-At and Rb-Sr methods of age-determination together with a re-evaluation of the stratigraphical position of critical specimens used by Holmes when constructing his 1947 time-scale indicated the need for a revision of this scale. Holmes published a revised time-scale in 1959, but the latest and most comprehensive revision was published by Kulp in 1961. This paper summarizes the evidence used by these and other authors in dating the limits of the geological periods. The beginning of the Cambrian period was set at about 600 m.y., the end of the Palaeozoic era at 230 m.y. (Kulp 1961) and 250 m.y. (Holmes 1959), and the end of the Mesozoic era at 63 m.y. (Kulp) and 70 m.y. (Holmes).
Potassium—argon decay constants and age tables
Authors: Smith Alan Gilbert
Published: September 2007

This paper outlines the physical measurements that determine the potassium–argon decay constants; compares the constants currently in use with those derived from the best physical measurements; and shows the magnitude of error in the time-scale due to different estimates of the constants and to a 5 per cent error in each of the constants. Tables are given which can be used by the non-specialist to relate K–Ar ages directly to the experimentally determined argon/potassium ratios using ‘standard’ constants.
The Silurian period
Authors: Strachan I.
Published: September 2007

Radiometric dates for the Silurian at present depend upon determinations on sediments. Available data suggest a time-span of up to about 50 m.y. for the Silurian period, with upper and lower limits of bout 390 m.y. and 440 m.y. Relations between graptolite zones and the time-scale imply a stratigraphical precision of about 1 m.y. Problems of international correlation are mentioned. The world maximum thickness of the system is estimated at about 70000 ft.
The Cambrian period
Authors: Cowie J. W.
Published: September 2007

Fifteen selected radiometric ages are used to construct a time-scale for the Cambrian System. Maximum thicknesses are not considered to be useful in constructing a Cambrian time-scale. Ages of 495 m.y. and 570 m.y. are suggested for the top and base of the system, with ages of 540 m.y. and 515 m.y. for the Lower-Middle and Middle-Upper Cambrian.
Surface Geochemical Exploration in the North Sea
Authors: Gevirtz J. L. , Carey B. D. , Blanco S. R.
Published: September 2007

Tenneco Oil Company has conducted extensive bottom sampling programmes over several known but undeveloped oil and gas fields in the North Sea. Samples over one example, Beatrice Field in U.K. waters, were distributed on an approximate 2 × 2 km grid over the entire licence block containing the field. Shipboard samples were collected from the ocean floor using a modified gravity-coring device that delivered cores up to 2 m in length. Overall core lengths varied from 0.5 m in hard sand to 2 m in clay. For geochemical analysis, samples were taken from the lower 0.5 m of the core.

In the laboratory, samples were analysed for light gases using gas chromatography. These results are expressed as parts per billion (10
12
) dry weight of sample. Fluorescence intensity over two peaks was recorded from hexane extracts. These results were expressed as relative peak intensities.

Data were subjected to a variety of analytical techniques including mapping of both individual variables and specific ratios, cross-plotting and regression of variable pairs to determine subtle interrelationships, and to a battery of multivariate pattern recognition techniques to isolate recurrent, mappable geochemical signatures.

After an independent assessment of the geochemical data was completed, the resultant geochemical interpretation was integrated with geological and geophysical data. Comparison of the geochemical maps with those produced as a result of geophysical and geological interpretation revealed remarkable similarity between the structural and geochemical interpretations. This suggests focussing of upward movement of hydrocarbons by geologic structure.

This exercise demonstrates that geochemical data of this type can greatly aid in the evaluation of the hydrocarbon potential structures, but should not be used alone as a prospecting method.
Petroleum Offshore Sniffer Exploration
Authors: Sigalove J.
Published: September 2007

The association of large-scale, visible (macro) seeps with oil and gas fields has been well known for many years. It is evident from the recent literature that developments in electronics and analytical techniques have been permitting more and more comprehensive geochemical analyses with a greater reliability and sensitivity. Low level, non-visible micro-seeps are now reliably detected and can be used to evaluate the hydrocarbon potential of a basin, to establish the association of hydrocarbons with individual structures, and to determine whether the reserves at depth are likely to be gas or oil prone.

Weisman at Gulf Oil Company describes a system which measures C
1
–C
4
hydrocarbons with a sensitivity of 5 × 10
−11
1 propane at STP 1
−1
seawater. The newest generation of ‘Sniffer’ systems manufactured and operated by Interocean Systems Inc. measures C
1
–C
8
hydrocarbons with resolution of the saturated and unsaturated isomers as well as resolutions of the straight chain, branch chain and cyclic isomers with a sensitivity of 5 × 10
−13
1
−1
octane at STP 1
−1
seawater. These advances in hardware in hardware coupled with new data processing techniques have permitted the establishment of a significant body of field data and experience over the years. It is evident from the data presented that these newer geochemical techniques and experience from field data have created the ability not only to detect the very low concentration micro-seeps, but also to interpret the data in a useful way. This is resulting in geochemistry playing a more significant role in exploration than ever before.
Some Geological Controls on Oil Composition in the U.K. North Sea
Authors: Cornford C. , Morrow J. A. , Turrington A. , Miles J. A. , Brooks J.
Published: September 2007

The U.K. North Sea contains a wide variety of reservoired oils, ranging from the biodegraded heavy oils, via mid-gravity crudes to light oils and condensates. Statistical data from a suite of U.K. North Sea oils gives an average API gravity of 36°, an average asphaltene content of 1.4% and an average saturate/aromatic ratio of 2.02. Averages for pristane/phytane, pristane/n-C
17
and phytane/n-C
18
are 1.24, 0.63 and 0.56 respectively. It is possible to explain the ocurrence of the vast majority of the U.K. North Sea crudes in terms of generation over a range of maturities from single source rock horizons (the Kimmeridge Clay Formation hot shales), followed by alteration during migration or within the reservoir. The source rocks are shown to be immature below 175°F (80°C); early mature between 175–225°F (80–107°C); mid-mature between 225–265°F (107–130°C) and late mature above 265°F (130°C). Early mature, full maturity spectrum and late mature oils are identified using maturity-controlled sterane and triterpane ratios established from the source rock studies, and are related to bulk properties such as API gravity and saturate/aromatic ratios.

Bacterial degradation in shallow cool reservoirs (less than 6000 ft; below 140°F (60°C)) is responsible for the majority of the heavy oil in the U.K. North Sea, while asphaltene enrichment is another mechanism for producing heavy oils.

Though the Kimmeridge Clay Formation hot shales are fairly homogeneous over the U.K. North Sea, molecular ratios such as the pristane/phytane ratio, the abundance of a C
28
hopane and a C
27
moretane can be used to correlate oils with specific facies of the generally homogeneous source rock.
Isotope Geochemistry of Natural Gases in Central Europe
Authors: Schoell M. , Whiticar M. J.
Published: September 2007

Three parameters of natural gases, i.e. the 13C/12C and D/H ratio of methane and the C
2
+ content have been arranged in new diagrams for the genetic characterisation of natural gases. The principal gas provinces of Central Europe are discussed with regard to the various processes of gas formation. Three gas producing geological ‘Stockwerke’ can be distinguished:

(1)

Palaeozoic: Producing mostly gases from coal measures (southern North Sea, the Netherlands, NW Germany)

(2)

Mesozoic: Predominantly gases associated with oils (northern North Sea, NW Germany, S Germany, Italy)

(3)

Tertiary: Bacterial gases reservoired in Tertiary basins and thermogenic or mixed gases accumulated in Tertiary and pre-Tertiary basins (S Germany, Austria, Italy).

Isotopic and molecular changes found in all gases investigated can be explained by processes during formation of the gases (‘primary gases’) and simple process of mixing of primary gases. Specifically, isotope patterns in young sedimentary basins argue against diffusion as a dominant process that controls compositional variations in natural gases.
Geochemical Observations and Oil Genesis in the German Alps and their foreland
Authors: Kuckelkorn K. , Wehner H. , Hufnagel H.
Published: September 2007

Currently attempts are being made to follow migration paths ‘upstream’ to deeply buried autochthonous Tertiary and Mesozoic source rocks below the Alpine over-thrusts using routine and geochemical exploration.

In the east the oil window probably lies much deeper to the south, however thermally mature strata rise westwards towards Lake Constance.

In the Eastern Molasse region, the basal Tertiary and Gault oils have a much higher maturity than the associated Tertiary source rocks, and also differ from the humic kerogen of the underlying Cretaceous. Their source may lie in Jurassic bituminous rocks, deeper and to the south.

In the Western Molasse region, oils in Tertiary and Mesozoic reservoirs form two families which can be correlated with source rocks of corresponding age occurring further south.
Pyrolysis-Mass Spectrometry in Coal Chemistry: a study of the coalification of vitrites and the typification of Australian Brown Coals
Authors: Schenck P. A. , de Leeuw J. W. , Viets T. C. , Haverkamp J.
Published: September 2007

Curie-point pyrolysis-mass spectrometry and Curie-point pyrolysis-gas chromatography-mass spectrometry have been applied to analyse a series of vitrites of different degrees of coalification and a number of samples taken from Australian brown coal seams (La Trobe Valley, Victoria).

The relationship between mass spectral data and degree of coalification for the first series and biochemical precursors for the second series can be established.
Spectral Correlation of Spore Coloration Standards
Authors: Smith P. M. R.
Published: September 2007

The optical examination of kerogen using transmitted light microscopy reveals a progressive and irreversible colour change with increasing thermal maturity. Such observations have resulted in various workers producing individual colour index scales, using diverse components of kerogen concentrates.

Three colour index scales are commonly quoted in the literature, namely Staplin’s Thermal Alteration Index (TAI), Robertson Research Spore Coloration Index (SCI), and Batten’s Colour Scale, which is also spore based.

Transmitted light spectra have been produced from the above mentioned sets of standard material, and a correlation of the different indices obtained.
The Use of Computerized Information in Britoil, Exploration Division
Authors: Baxter G. G.
Published: September 2007

The Geodata Group of the Exploration Division of Britoil plc maintains six computerized information systems on behalf of the explorationists in the Company. These systems contain data about wells, licences, field studies, well exchange, shotpoint locations and 3-D grids. The wells system contains basic reference data and drilling summaries. The licence system consists of complete licence details as well as co-ordinate information for plotting purposes. The field studies system contains pairs of files, geological/petrophysical data and deviation survey data, for all wells in each field covered. The well exchange system is a list of what wells were ‘given’ for those wells ‘obtained’. The shotpoint locations system consists of navigation data obtained during seismic surveys from which shotpoint basemaps are directly produced. The 3-D grids are generated by the Radian Corporation package CPS-1 and contain two-way seismic times, seismic velocities or structural depth surfaces over fields or prospects. All the systems have developed in response to specific requirements of geologists or geophysicists. A database requirements review was undertaken during 1982 and the results of this will be built in to a proposed integrated information system. Because of this transition only an abstract of the paper is presented here.
Diapiric ascent and cooling of a sillimanite gneiss dome revealed by40Ar/39Ar thermochronology: the Kigluaik Mountains, Seward Peninsula, Alaska
Authors: Calvert Andrew T. , Gans Phillip B. , Amato Jeffrey M.
Published: September 2007

The upper amphibolite to granulite facies Kigluaik gneiss dome cooled rapidly in late Cretaceous time as it rose through the crust and was emplaced against the older blueschist-greenschist facies Nome Group.40Ar/39Ar data from metamorphic rocks reveal prolonged moderately rapid cooling histories that vary somewhat with structural depth and geographical position. Hornblende ages (Tcc.535°C) range from 86 to 82 Ma, mica ages (Tcc.300–400°C) range from 85 to 83 Ma, and K-feldspar spectra yield age gradients that record cooling fromc.300° toc.150°C between 82 and 65 Ma. These high-precision cooling ages on hornblende, white mica and biotite, and detailed temperature-time curves obtained from diffusion modelling of K-feldspar age spectra allow us to reconstruct the 3D geometry of isotherms during cooling and local reheating of the gneiss dome. Isotherms were parallel to lithological contacts during high-temperature cooling, then became subhorizontal in present-day coordinates as layering was domed byc.84 Ma. Low-temperature cooling (300–150°C) of the gneiss dome is asymmetrical, with the north side cooling several million years before the south side. The contact between high-grade gneisses of the Kigluaik Mountains and surrounding lower-grade rocks is not a fault, but rather a steep metamorphic field gradient where closely spaced Barrovian isograds and partially reset mica ages document progressive thermal overprint of the older blueschist-greenschist facies Nome Group rocks. These combined geological and thermochronological data are most compatible with a model wherein the Kigluaik gneiss dome rose diapirically from mid-crustal levels between 91 Ma andc.82 Ma and cooled through low temperatures differentially as it was tilted gently southward between 83 and 65 Ma.
Exposure of deep, dense rocks: interplay between erosion and sinking
Authors: Glazner Allen F.
Published: September 2007

A numerical model of the interplay between viscous sinking and erosion predicts that the ultimate fate of dense rock bodies in the crust is a sensitive function of erosion rate and of the body’s radius, density, and initial depth of emplacement. If all of these variables save one are held constant, the trajectories taken by the body on a depth-time plot diverge widely about a critical value of the remaining variable. For example, if erosion rate, depth, and density are held constant, there is a critical value of the body’s radius below which it will be carried to the Earth’s surface by erosion and above which it will plummet to neutral buoyancy in the deep crust. This critical sensitivity may explain, for example, why dense plutons larger than a few kilometres in diameter are rare in plutonic terranes. The calculations indicate that exceptionally high erosion or tectonic denudation rates, on the order of 10 km Ma
−1
or more, may be necessary to bring dense bodies to the surface before they sink through less dense crust.
Thermal and mechanical models for the structural and metamorphic evolution of the Zanskar High Himalaya
Authors: Searle M. P. , Waters D. J. , Dransfield M. W. , Stephenson B. J. , Walker C. B. , Walker J. D. , Rex D. C.
Published: September 2007

The regional Barrovian facies metamorphic rocks of the High Himalayan Slab in Zanskar are bounded along the base by the southwest vergent Main Central Thrust (MCT) with its characteristic zone of inverted isograds, and along the top of the slab by the northeast dipping Zanskar Shear Zone (ZSZ), part of the South Tibetan Detachment (STD) System of normal faults. Summarized here are the results of systematic mapping combined with detailedP-T-tdata from the Zanskar Himalaya, and models for the thermal and mechanical evolution of the middle and deep crustal rocks of the Himalaya are discussed. Temperatures and pressures increase dramatically up-structural section across the MCT Zone from biotite through garnet, staurolite and kyanite grade to sillimanite + muscovite, and decrease along the top of the stab beneath the ZSZ normal faults. In Zanskar, peakP-Tconditions of the M1 kyanite-grade rocks are 550–680°C and 9.5–10.5kbar, and M2 sillimanite-grade gneisses were formed at 650–770°C and 4.5–7 kbar. The core of the High Himalayan Zone is a 30 km wide zone of sillimanite + K-feldspar-grade gneisses, migmatites and anatectic leucogranites with a right way-up isograd sequence above and an inverted sequence below.

Thermal models of thrusting a hot slab over a cold slab and frictional heating along the MCT are not supported by the structural and thermobarometric data. Mechanical models of post-metamorphic structural disruption by folding and thrusting of a pre-existing, right way-up metamorphic sequence are compatible with structural andP-Tdata. Ductile shearing along the MCT Zone has structurally condensed the isograds, and final motion along the ZSZ postdated leucogranite crystallization (21.5-19.5 Ma; U-Pb monazite ages) and emplacement in the footwall. Crustal shortening and thickening, resulting in prograde metamorphism, lasted from the time of India-Asia collision at 54-50Ma until at least 30-25 Ma. Crustal melting is constrained at 20.8-19.5 Ma along the core of the stab. Late stage out-of-sequence thrusting within the High Himalayan Slab effectively maintained the crustal thickening process enablingP-Tconditions to remain high for 10-5 Ma. Rapid exhumation between 21-18.5 Ma was accompanied by removal of 18–25 km of overburden by erosion at exhumation rates of 6–10 mm yr−1. This early Miocene period of high exhumation rates, rapid erosion and exhumation of rocks buried at τ25 km depth is interpreted to indicate the uplift of high mountains and erosion of deep valleys, probably with high precipitation during that time.
Analysis of Topology Aggregation techniques for QoS routing
Authors: Uludag Suleyman , Lui King-Shan , Nahrstedt Klara , Brewster Gregory
Published: September 2007

We study and compare topology aggregation techniques used in QoS routing. Topology Aggregation (TA) is defined as a set of techniques that abstract or summarize the state information about the network topology to be exchanged, processed, and maintained by network nodes for routing purposes. Due to scalability, aggregation techniques have been an integral part of some routing protocols. However, TA has not been studied extensively except in a rather limited context. With the continuing growth of the Internet, scalability issues of QoS routing have been gaining importance. Therefore, we survey the current TA techniques, provide methodology to classify, evaluate, and compare their complexities and efficiencies.
A control theoretic approach to energy-efficient pipelined computation in MPSoCs
Authors: Carta Salvatore , Alimonda Andrea , Pisano Alessandro , Acquaviva Andrea , Benini Luca
Published: September 2007

In this work, we describe a control theoretic approach to dynamic voltage/frequency scaling (DVFS) in a pipelined MPSoC architecture with soft real-time constraints, aimed at minimizing energy consumption with throughput guarantees. Theoretical analysis and experiments carried out on a cycle-accurate, energy-aware, and multiprocessor simulation platform are provided. We give a dynamic model of the system behavior which allows to synthesize linear and nonlinear feedback control schemes for the run-time adjustment of the core frequencies. We study the characteristics of the proposed techniques in both transient and steady-state conditions. Finally, we compare the proposed feedback approaches and local DVFS policies from an energy consumption viewpoint.
Three empirical studies on estimating the design effort of Web applications
Authors: Baresi Luciano , Morasca Sandro
Published: September 2007

Our research focuses on the effort needed for designing modern Web applications. The design effort is an important part of the total development effort, since the implementation can be partially automated by tools.

We carried out three empirical studies with students of advanced university classes enrolled in engineering and communication sciences curricula. The empirical studies are based on the use of W2000, a special-purpose design notation for the design of Web applications, but the hypotheses and results may apply to a wider class of modeling notations (e.g., OOHDM, WebML, or UWE). We started by investigating the relative importance of each design activity. We then assessed the accuracy of
a priori
design effort predictions and the influence of a few process-related factors on the effort needed for each design activity. We also analyzed the impact of attributes like the size and complexity of W2000 design artifacts on the total effort needed to design the user experience of web applications. In addition, we carried out a finer-grain analysis, by studying which of these attributes impact the effort devoted to the steps of the design phase that are followed when using W2000.
An analysis approach for testing exception handling programs
Authors: Jiang Shujuan , Jiang Yuanpeng
Published: September 2007

Exception handling is a powerful mechanism that separates the error handling code from normal code. However, incorrect usage of exception will bring about more potential faults in the code. Based on the study of exception model of C++, the paper proposes a precise and efficient representation of programs with exception handling constructs---Exception Control Flow Graph, which can represent explicitly the implicit control flow of exception and exception propagation path. Then it presents the structure testing criteria of programs with exception handling constructs based on the representation method, and gives the computing method. The approach overcomes the limitations of previous incorrect analysis because of failing to account for the effects of exception handling constructs.
Why 'nearshore' means that distance matters
Authors: Carmel Erran , Abbott Pamela
Published: September 2007

When sourcing abroad, a growing number of companies now weigh whether the location is near vs. far.
Social phishing
Authors: Jagatic Tom N. , Johnson Nathaniel A. , Jakobsson Markus , Menczer Filippo
Published: September 2007

Sometimes a "friendly" email message tempts recipients to reveal more online than they otherwise would, playing right into the sender's hand.
Reflections and trends in the expansion of cellular wireless services in the U.S. and China
Authors: Passerini Katia , Patten Karen , Bartolacci Michael R. , Fjermestad Jerry
Published: September 2007

Charting the evolution of business capabilities and communication technology and standards.
Heterotrimeric G Protein Signaling in Filamentous Fungi
Authors: Li Liande , Wright Sara J. , Krystofova Svetlana , Park Gyungsoon , Borkovich Katherine A.
Published: September 2007

Filamentous fungi are multicellular eukaryotic organisms known for nutrient recycling as well as for antibiotic and food production. This group of organisms also contains the most devastating plant pathogens and several important human pathogens. Since the first report of heterotrimeric G proteins in filamentous fungi in 1993, it has been demonstrated that G proteins are essential for growth, asexual and sexual development, and virulence in both animal and plant pathogenic filamentous species. Numerous G protein subunit and G protein–coupled receptor genes have been identified, many from whole-genome sequences. Several regulatory pathways have now been delineated, including those for nutrient sensing, pheromone response and mating, and pathogenesis. This review provides a comparative analysis of G protein pathways in several filamentous species, with discussion of both unifying themes and important unique signaling paradigms.
α-Actinin-1 phosphorylation modulates pressure-induced colon cancer cell adhesion through regulation of focal adhesion kinase-Src interaction
Authors: Craig David H. , Haimovich Beatrice , Basson Marc D.
Published: September 2007

Physical forces including pressure, strain, and shear can be converted into intracellular signals that regulate diverse aspects of cell biology. Exposure to increased extracellular pressure stimulates colon cancer cell adhesion by a β1-integrin-dependent mechanism that requires an intact cytoskeleton and activation of focal adhesion kinase (FAK) and Src. α-Actinin facilitates focal adhesion formation and physically links integrin-associated focal adhesion complexes with the cytoskeleton. We therefore hypothesized that α-actinin may be necessary for the mechanical response pathway that mediates pressure-stimulated cell adhesion. We reduced α-actinin-1 and α-actinin-4 expression with isoform-specific small interfering (si)RNA. Silencing of α-actinin-1, but not α-actinin-4, blocked pressure-stimulated cell adhesion in human SW620, HT-29, and Caco-2 colon cancer cell lines. Cell exposure to increased extracellular pressure stimulated α-actinin-1 tyrosine phosphorylation and α-actinin-1 interaction with FAK and/or Src, and enhanced FAK phosphorylation at residues Y397 and Y576. The requirement for α-actinin-1 phosphorylation in the pressure response was investigated by expressing the α-actinin-1 tyrosine phosphorylation mutant Y12F in the colon cancer cells. Expression of Y12F blocked pressure-mediated adhesion and inhibited the pressure-induced association of α-actinin-1 with FAK and Src, as well as FAK activation. Furthermore, siRNA-mediated reduction of α-actinin-1 eliminated the pressure-induced association of α-actinin-1 and Src with β1-integrin receptor, as well as FAK-Src complex formation. These results suggest that α-actinin-1 phosphorylation at Y12 plays a crucial role in pressure-activated cell adhesion and mechanotransduction by facilitating Src recruitment to β1-integrin, and consequently the association of FAK with Src, to enhance FAK phosphorylation.
Pregnancy increases baroreflex-independent GABAergic inhibition of the RVLM in rats
Authors: Kvochina Lyudmyla , Hasser Eileen M. , Heesch Cheryl M.
Published: September 2007

During baroreceptor unloading, sympathoexcitation is attenuated in near-term pregnant compared with nonpregnant rats. Alterations in balance among different excitatory and inhibitory inputs within central autonomic pathways likely contribute to changes in regulation of sympathetic outflow in pregnancy. Both baroreflex-dependent and baroreflex-independent GABAergic inputs inhibit sympathoexcitatory neurons within rostral ventrolateral medulla (RVLM). The present experiments tested the hypothesis that influence of baroreflex-independent GABAergic inhibition of RVLM is greater in pregnant compared with nonpregnant rats. Afferent baroreceptor inputs were eliminated by bilateral sinoaortic denervation in inactin-anesthetized rats. In pregnant compared with nonpregnant rats, baseline mean arterial pressure (MAP) was lower (pregnant = 75 ± 6 mmHg, nonpregnant = 115 ± 7 mmHg) and heart rate was higher (pregnant = 381 ± 10 beats/min, nonpregnant = 308 ± 10 beats/min). Pressor and sympathoexcitatory [renal sympathetic nerve activity, (RSNA)] responses due to bilateral GABAA receptor blockade (bicuculline, 4 mM, 100 nl) of the RVLM were greater in pregnant rats (ΔMAP: pregnant = 101 ± 4 mmHg, nonpregnant = 80 ± 6 mmHg; ΔRSNA: pregnant = 182 ± 23% control, nonpregnant = 133 ± 10% control). Unexpected transient sympathoexcitatory effects of angiotensin AT1 receptor blockade in the RVLM were greater in pregnant rats. Although excitatory responses to bicuculline were attenuated by prior RVLM AT1 receptor blockade in both groups, pressor responses to disinhibition of the RVLM remained augmented in pregnant rats. Increased influence of baroreflex-independent GABAergic inhibition in RVLM could contribute to suppressed sympathoexcitation during withdrawal of arterial baroreceptor input in pregnant animals.
Photoperiodic and hormonal influences on fur density and regrowth in two hamster species
Authors: Paul Matthew J. , George Nicole T. , Zucker Irving , Butler Matthew P.
Published: September 2007

Temperate and boreal mammals undergo seasonal changes in pelage that facilitate thermoregulation in winter and summer. We investigated photoperiodic influences on pelage characteristics of male Siberian and Syrian hamsters. Fur density (mg fur/cm2 skin) was measured by weighing the shavings of fur patches removed from the dorsal and ventral surfaces of hamsters maintained in long days (LDs) or transferred to short days (SDs). Patches were reshaved 3 wk later to assess fur regrowth (mg regrown fur/cm2 skin). Fur density was greater in SD than in LD Siberian hamsters after 11 wk of differential phototreatment. The onset of increased fur density in SDs was accompanied by a transient increase in fur regrowth (11–14 wk on the dorsal surface and 7–10 and 11–14 wk on the ventral surface), suggestive of a seasonal molting process. Fur density, body mass, and pelage color of Siberian hamsters returned to values characteristic of LD males after a similar duration of prolonged (>27 wk) SD treatment and appear to be regulated by a similar or common interval-timing mechanism. In Syrian hamsters, dorsal fur density, fur regrowth, and hair lengths were greater in SD than in LD males. Castration increased and testosterone (T) treatment decreased dorsal and ventral fur regrowth in LD and SD hamsters, but the effects of T manipulations on fur density were limited to a decrease in dorsal fur density after T treatment. Decreased circulating T in SDs likely contributes to the seasonal molt of male hamsters by increasing the rate of fur growth during the transition to the winter pelage.
Effects of early postnatal hypernutrition on nephron number and long-term renal function and structure in rats
Authors: Boubred Farid , Buffat Christophe , Feuerstein Jean-Marc , Daniel Laurent , Tsimaratos Michel , Oliver Charles , Lelièvre-Pégorier Martine , Simeoni Umberto
Published: September 2007

Various antenatal events impair nephrogenesis in humans as well as in several animal models. The consecutive low nephron endowment may contribute to an increased risk for cardiovascular and renal diseases in adulthood. However, little knowledge is available on the influence of the postnatal environment, especially nutrition, on nephrogenesis. Moreover, the consequences of early postnatal nutrition in late adulthood are not clear. We used a model of early postnatal overfeeding (OF) induced by reduction of litter size (3 pups/litter) in rats. Systolic blood pressure (SBP; plethysmography), glomerular filtration rate (clearance of creatinine), glomerular number and volume, and glomerulosclerosis were evaluated in 22-mo-old aging offspring. Early postnatal OF was associated with increased weight gain during the suckling period (+40%, P < 0.01) and a 20% increase in glomerular number ( P < 0.05). However, an increase in SBP at 12 mo by an average of 18 mmHg and an increase in proteinuria (2.6-fold) and glomerulosclerosis at 22 mo of age were observed in OF male offspring compared with controls. In conclusion, early postnatal OF in the rat enhances postnatal nephrogenesis, but elevated blood pressure and glomerulosclerosis are still observed in male adults. Factors other than glomerular number reduction are likely to contribute to the arterial hypertension induced by early postnatal OF.
Isoflurane mediates protection from renal ischemia-reperfusion injury via sphingosine kinase and sphingosine-1-phosphate-dependent pathways
Authors: Kim Minjae , Kim Mihwa , Kim Nala , D'Agati Vivette D. , Emala Charles W. , Lee H. Thomas
Published: September 2007

The inhalational anesthetic isoflurane has been shown to protect against renal ischemia-reperfusion (IR) injury. Previous studies demonstrated that isoflurane modulates sphingolipid metabolism in renal proximal tubule cells. We sought to determine whether isoflurane stimulates sphingosine kinase (SK) activity and synthesis of sphingosine-1-phosphate (S1P) in renal proximal tubule cells to mediate renal protection via the S1P signaling pathway. Isoflurane anesthesia reduced the degree of renal failure and necrosis in a murine model of renal IR injury. This protection with isoflurane was reversed by SK inhibitors (DMS and SKI-II) as well as an S1P1receptor antagonist ( VPC23019 ). In addition, mice deficient in SK1 enzyme were not protected from IR injury with isoflurane. SK activity as well as SK1 mRNA expression increased in both cultured human proximal tubule cells (HK-2) and mouse kidneys after exposure to isoflurane. Finally, isoflurane increased the generation of S1P in HK-2 cells. Taken together, our findings indicate that isoflurane activates SK in renal tubule cells and initiates S1P→S1P1receptor signaling to mediate the renal protective effects. Our findings may help to unravel the cellular signaling pathways of volatile anesthetic-mediated renal protection and lead to new therapeutic applications of inhalational anesthetics during the perioperative period.
Functional Connectivity Between Auditory Areas Field L and CLM and Song System Nucleus HVC in Anesthetized Zebra Finches
Authors: Shaevitz Sarita S. , Theunissen Frédéric E.
Published: September 2007

A key discovery that has emerged from studies of the vocal system in songbirds is that neurons in these regions respond preferentially to playback of the bird's own song (BOS). This BOS selectivity is not a general property of neurons in primary and secondary auditory forebrain regions, field L and caudolateral mesopallium (CLM). Moreover, anatomical studies have been unable to conclusively define a direct projection from field L and/or CLM to HVC, a central structure for integrating sensory and motor information in the vocal system. To examine the communication between these regions, we used simultaneous dual-electrode recording in anesthetized male zebra finches and cross-correlation analysis to estimate the functional connectivity between auditory areas, field L and CLM, and HVC. We found that ≥18% of neurons in field L and 33% of neurons in CLM are functionally connected to HVC, most with auditory forebrain leading-HVC latencies ranging from 0.5 to 15 ms. These results indicate that field L and CLM communicate extensively with HVC through both direct and indirect anatomical connections. To further explore the role of the auditory forebrain cells that are functionally connected with HVC, we assessed their responsiveness and selectivity for a variety of natural and synthetic auditory stimuli. We found that field L and CLM neurons that are functionally connected to HVC exhibit generic auditory forebrain properties including the lack of BOS selectivity. This finding puts further constraints on the neural architecture and the nature of the nonlinearity that leads to BOS-selective auditory responses in the vocal control nuclei.
Layer V Neurons in Mouse Cortex Projecting to Different Targets Have Distinct Physiological Properties
Authors: Hattox Alexis M. , Nelson Sacha B.
Published: September 2007

Layer V pyramidal neurons are anatomically and physiologically heterogeneous and project to multiple intracortical and subcortical targets. However, because most physiological studies of layer V pyramidal neurons have been carried out on unidentified cells, we know little about how anatomical and physiological properties relate to subcortical projection site. Here we combine neuroanatomical tract tracing with whole cell recordings in mouse somatosensory cortex to test whether neurons with the same projection target form discrete subpopulations and whether they have stereotyped physiological properties. Our findings indicate that corticothalamic and -trigeminal neurons are two largely nonoverlapping subpopulations, whereas callosal and corticostriatal neurons overlap extensively. The morphology as well as the intrinsic membrane and firing properties of corticothalamic and corticotrigeminal neurons differ from those of callosal and corticostriatal neurons. In addition, we find that each class of projection neuron exhibits a unique compliment of hyperpolarizing and depolarizing afterpotentials that further suggests that cortical neurons with different subcortical targets are distinct from one another.
Subdivision-Specific Responses of Neurons in the Nucleus of the Tractus Solitarius to Activation of Mu-Opioid Receptors in the Rat
Authors: Poole Sarah L. , Deuchars Jim , Lewis David I. , Deuchars Susan A.
Published: September 2007

Microinjection of opioid receptor agonists into the nucleus tractus solitarius (NTS) has differential effects on cardiovascular, respiratory, and gastrointestinal responses. This can be achieved either by presynaptic modulation of inputs onto neurons or by postsynaptic activation of receptors on neurons in specific regions. Therefore we sought to determine whether responses of neurons to activation of opioid receptors were dependent on their location within the NTS. Using whole cell patch-clamp recordings from neurons within the NTS, the mu opioid receptor (MOR) agonist [d-Ala2, N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO, 100 nM) hyperpolarized a proportion of neurons in the medial, dorsomedial and dorsolateral NTS, whereas no postsynaptic responses were observed in remaining subdivisions. DAMGO reduced the amplitude of solitary tract-evoked excitatory postsynaptic potentials (EPSPs) in all neurons tested, regardless of subdivision. The kappa opioid receptor (KOR) agonist U69593 (10–20 μM) also hyperpolarized a small fraction of neurons (6/79) and decreased the amplitude of EPSPs in 50% of neurons. In contrast, the delta-opioid receptor agonist DPDPE (1–4 μM) had no presynaptic or postsynaptic effects on NTS neurons even after preincubation with bradykinin. Anatomical data at the light and electron microscopic level complemented electrophysiological observations with respect to MOR location and further showed that MORs were present at both presynaptic and postsynaptic sites in the dorsolateral NTS, often at the same synapse. These data demonstrate site specific responses of neurons to activation of MORs and KORs, which may underlie their ability to modulate different autonomic reflexes.
Incorporating Voluntary Knee Flexion Into Nonanticipatory Balance Corrections
Authors: Oude Nijhuis Lars B. , Bloem Bastiaan R. , Carpenter Mark G. , Allum John H. J.
Published: September 2007

Knee movements play a critical role in most balance corrections. Loss of knee flexibility may cause postural instability. Conversely, trained voluntary knee flexions executed during balance corrections might help to overcome balance deficits. We examined whether bilateral knee flexion could be added to automatic balance corrections generated by sudden balance perturbations. We investigated how this could be achieved and whether it improved or worsened balance control. Twenty-four healthy subjects participated in three different test conditions, in which they had to flex their knees following an auditory cue (VOLUNTARY condition), had to restore their balance in response to multidirectional rotations of a support surface (REACTIVE condition), or the combination of these two (COMBINED condition). A new variable set (PREDICTED), calculated as the mathematical sum of VOLUNTARY and REACTIVE, was compared with the COMBINED variable set. COMBINED responses following forward rotations were close to PREDICTED, or greater, suggesting adequate integration of knee flexion into the automatic balance reactions. For backward rotations, the COMBINED condition resulted in several near-falls, and this was generally associated with smaller knee flexion and smaller EMG responses. Subjects compensated by using greater trunk flexion and arm movements. Activity in several muscles displayed earlier onsets for the COMBINED condition following backward rotations. We conclude that healthy adults can incorporate voluntary knee flexion into their automatic balance corrections and that this depends on the direction of the postural perturbation. These findings highlight the flexibility of the human balance repertoire and underscore both the advantages and limitations of using trained voluntary movements to aid balance corrections in man.
Differences in postingestive metabolism of glutamate and glycine between C57BL/6ByJ and 129P3/J mice
Authors: Ji Hong , Bachmanov Alexander A.
Published: September 2007

Amino acids are essential nutrients for living organisms. There are genetic differences in voluntary consumption of amino acids among mouse strains. In two-bottle preference tests, C57BL/6ByJ (B6) mice consume more glutamate (Glu) and glycine (Gly) solutions than do 129P3/J (129) mice. To examine the role of postingestive metabolism of these amino acids in regulation of their intake, we compared metabolism of orally administered Glu and Gly in B6 and 129 mice. After administration of Glu, there were increases in circulating glucose and insulin in B6 mice, whereas 129 mice had elevated blood alanine and body temperature. After ingestion of Gly, B6 mice had increases in blood glucose, whereas there was an elevation of body temperature in 129 mice. These data suggest that B6 mice preferentially convert ingested Glu and Gly to glucose in contrast to 129 mice, which preferentially use them for thermogenesis. This study strongly supports the hypothesis that the metabolic fate of a nutrient plays an important regulatory role in control of its intake. This is the first detailed study of mouse strain differences in amino acid metabolism.
Administration of PDE4 Inhibitors Suppressed the Pannus-Like Inflammation by Inhibition of Cytokine Production by Macrophages and Synovial Fibroblast Proliferation
Authors: Kobayashi Katsuya , Suda Toshio , Manabe Haruhiko , Miki Ichiro
Published: September 2007

A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1β, TNF-α, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-αand IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.
Contribution of Hierarchical Clustering Techniques to the Modeling of the Geographic Distribution of Genetic Polymorphisms Associated with Chronic Inflammatory Diseases in the Québec Population
Authors: Madore A.-M. , Houde L. , Vézina H. , Vohl M.-C. , Pérusse L. , Mior N. , Connelly P.W. , Laberge C. , Gaudet D. , Laprise C.
Published: September 2007

Objectives: The purpose of this project was to evaluate the potential of the downward hierarchical clustering analysis (DHCA) for studying genetic heterogeneity, i.e. differences in allele frequency in subpopulations, such as the 15 public health regions of the province of Québec (Canada). Methods: The study relied on an anonymized sample of 1,680 individuals who had participated in the Québec Heart Health Survey in 1990–1991. The genotyping of 11 variants in 8 candidate genes known to be involved in chronic inflammatory diseases, namely asthma and cardiovascular diseases, was performed using the amplification refractory mutation system and restriction fragment length polymorphism techniques. Only variants showing an allelic frequency >2% in the Québec Heart Health Survey (n = 8) were selected. DHCA techniques were then applied to model the geographical distribution of these 8 genetic variants in 15 Québec public health regions and to study genetic heterogeneity. Results: The DHCA allowed to group public health regions and gene variants on the basis of genetic variability. For both asthma and cardiovascular diseases, 3 significant clusters of public health regions and 1 cluster of gene variants were identified. Discussion: This study suggests that DHCA might be useful in studying genetic heterogeneity at the population level and for public health activities.