bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Breast Lymphoma: Results of a Controlled Clinical Trial
Authors: Avilés Agustin , Delgado Serafin , Nambo M. Jesús , Neri Natividad , Murillo Edgar , Cleto Sergio
Published: September 2005

Objectives: To assess the efficacy and toxicity of the most employed therapeutic approaches in the treatment of primary breast lymphoma (PBL). Methods: Ninety-six patients with PBL in the early stage (I or II) were enrolled to receive radiotherapy (45 Gy); chemotherapy (six cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), every 21 days), or combined therapy. Results: Complete response was achieved in 20 of 30 patients treated with radiotherapy, 19 of 32 who were treated with chemotherapy and 30 of 34 in the combined arm (p < 0.01). Actuarial curves at 10 years showed that event-free survival was 50, 57 and 83%, respectively (p < 0.01). Actuarial curves for overall survival were 50, 50 and 76% (p < 0.01), respectively. The most common site of relapse was the central nervous system. Acute toxicity was mild. Until now, no second neoplasm or acute leukemia has been observed. Conclusions: In our study combined therapy is the best treatment in this special setting of patients; with improvement in event-free survival and overall survival without acute or severe late side effects. Prophylaxis to the central nervous system will be considered in the initial treatment to improve outcome.
Myoendothelial Coupling Is Not Prominent in Arterioles Within the Mouse Cremaster Microcirculation In Vivo
Authors: Siegl Daniel , Koeppen Michael , Wölfle Stephanie E. , Pohl Ulrich , de Wit Cor
Published: September 2005

A smooth muscle hyperpolarization is essential for endothelium-dependent hyperpolarizing factor–mediated dilations. It is debated whether the hyperpolarization is induced by a factor (endothelium-derived hyperpolarizing factor) and/or is attributable to direct current transfer from the endothelium via myoendothelial gap junctions. Here, we measured membrane potential in endothelial cells (EC) and smooth muscle cells (SMC) in vivo at rest and during acetylcholine (ACh) application in the cremaster microcirculation of mice using sharp microelectrodes before and after application of specific blockers of Ca
2+
-dependent K
+
channels (K
Ca
). Moreover, diameter changes in response to ACh were studied. Membrane potential at rest was lower in EC than SMC (−46.6±1.0 versus −36.5±1.0mV,
P
<0.05). Bolus application of ACh induced robust hyperpolarizations in EC and SMC, but the amplitude (11.1±0.9 versus 5.1±0.9mV,
P
<0.05) and duration of the response (10.7±0.8 versus 7.5±1.0s,
P
<0.05) were larger in EC. Blockers of large conductance K
Ca
(charybdotoxin or iberiotoxin) abrogated ACh-induced hyperpolarizations in SMC but did not alter endothelial hyperpolarizations. In contrast, apamin, a blocker of small conductance K
Ca
abolished ACh-induced hyperpolarizations in EC and had only small effects on SMC. ACh-induced dilations were strongly attenuated by iberiotoxin but only slightly by apamin. We conclude that myoendothelial coupling in arterioles in vivo in the murine cremaster is weak, as EC and SMC behaved electrically different. Small conductance K
Ca
mediate endothelial hyperpolarization in response to ACh, whereas large conductance K
Ca
are important in SMC. Because tight myoendothelial coupling was found in vitro in previous studies, we suggest that it is differentially regulated between vascular beds and/or by mechanisms acting in vivo.
Neuroprotective Properties of the Natural Vitamin E α-Tocotrienol
Authors: Khanna Savita , Roy Sashwati , Slivka Andrew , Craft Tara K.S. , Chaki Soma , Rink Cameron , Notestine Margaret A. , DeVries A. Courtney , Parinandi Narasimham L. , Sen Chandan K.
Published: September 2005

Background and Purpose—

The current work is based on our previous finding that in neuronal cells, nmol/L concentrations of α-tocotrienol (TCT), but not α-tocopherol (TCP), blocked glutamate-induced death by suppressing early activation of c-Src kinase and 12-lipoxygenase.

Methods—

The single neuron microinjection technique was used to compare the neuroprotective effects of TCT with that of the more widely known TCP. Stroke-dependent brain tissue damage was studied in 12-Lox-deficient mice and spontaneously hypertensive rats orally supplemented with TCT.

Results—

Subattomole quantity of TCT, but not TCP, protected neurons from glutamate challenge. Pharmacological as well as genetic approaches revealed that 12-Lox is rapidly tyrosine phosphorylated in the glutamate-challenged neuron and that this phosphorylation is catalyzed by c-Src. 12-Lox-deficient mice were more resistant to stroke-induced brain injury than their wild-type controls. Oral supplementation of TCT to spontaneously hypertensive rats led to increased TCT levels in the brain. TCT-supplemented rats showed more protection against stroke-induced injury compared with matched controls. Such protection was associated with lower c-Src activation and 12-Lox phosphorylation at the stroke site.

Conclusion—

The natural vitamin E, TCT, acts on key molecular checkpoints to protect against glutamate- and stroke-induced neurodegeneration.
Analysis of an Idealized, Three-Dimensional Diabatic Rossby Vortex: A Coherent Structure of the Moist Baroclinic Atmosphere
Authors: Moore Richard W. , Montgomery Michael T.
Published: September 2005

The fifth-generation Pennsylvania State University–National Center for Atmospheric Research (PSU–NCAR) Mesoscale Model (MM5) is used to conduct a number of idealized numerical simulations to confirm recent findings of an alternate growth mechanism in a moist baroclinic environment to that of traditional baroclinic instability. In this alternate growth scenario, disturbance growth depends on the presence of sufficient environmental moisture and baroclinicity. The resulting coherent structure, termed a diabatic Rossby vortex (DRV), grows as a result of an approximate phase locking and mutual amplification of two diabatically generated potential vorticity (PV) anomalies: a low-level positive (cyclonic) PV anomaly and a midtropospheric negative (anticyclonic) PV anomaly.

The three-dimensional structure of a DRV is found to be qualitatively very similar to that seen in previous two-dimensional model simulations. The most apparent structural discrepancy from the two-dimensional model is the increased strength of the midtropospheric negative PV anomaly in the three-dimensional simulations.

A sensitivity study is undertaken to better understand the dependence of the DRV dynamics on some of the more pertinent environmental and perturbation vortex parameters, and to quantify the effect of each parameter. The resulting intensity of a DRV is most sensitive to the magnitude of environmental baroclinicity and moisture content, while the vertical profile of moisture is the most dominant factor in determining the characteristic depth of the DRV. It is also found that the “size” and “amplitude” of a precursor perturbation vortex are important factors in determining the track and intensity of the ensuing DRV.
The Dynamics of Phase Locking
Authors: Krishnamurti T. N. , Chakraborty D. R.
Published: September 2005

Many low-frequency phenomena such as the Madden–Julian oscillation (MJO) or the El Niño–Southern Oscillation (ENSO) exhibit rapid growth where they appear to be undergoing a phase locking with other time scales such as the annual cycle. The purpose of this paper is to illustrate an example of phase locking of two different time scales. In this instance it is shown that during such epochs of phase locking a large increase in nonlinear energy exchange occurs from one time scale to the other. This paper utilizes the ECMWF Re-Analysis (ERA-40) datasets for the year 2001 to examine this problem. This study is a sequel to a recent modeling study where the maintenance of the MJO time scale was examined from scale interactions, especially with synoptic-scale waves with ∼2–7 day periods. It was shown that a pair of waves on the synoptic time scale can satisfy certain selection rules and undergo triad interactions (kinetic energy to kinetic energy exchanges) and transfer energy. This present study illustrates the fact that during epochs of phase locking such nonlinear interactions can become very large, thus portraying the importance of phase locking. These explosive exchanges are shown from two perspectives: an approach based on kinetic energy exchanges in the frequency domain and another that invokes the boundary layer dynamics in the frequency domain.
Zonal and Vertical Structure of the Madden–Julian Oscillation
Authors: Kiladis George N. , Straub Katherine H. , Haertel Patrick T.
Published: September 2005

A statistical study of the three-dimensional structure of the Madden–Julian oscillation (MJO) is carried out by projecting dynamical fields from reanalysis and radiosonde data onto space–time filtered outgoing longwave radiation (OLR) data. MJO convection is generally preceded by low-level convergence and upward motion in the lower troposphere, while subsidence, cooling, and drying prevail aloft. This leads to moistening of the boundary layer and the development of shallow convection, followed by a gradual and then more rapid lofting of moisture into the middle troposphere at the onset of deep convection. After the passage of the heaviest rainfall, a westerly wind burst region is accompanied by stratiform precipitation, where lower tropospheric subsidence and drying coincide with continuing upper tropospheric upward motion. The evolution of the heating field leads to a temperature structure that favors the growth of the MJO. The analysis also reveals distinct differences in the vertical structure of the MJO as it evolves, presumably reflecting changes in its vertical heating profile, phase speed, or the basic-state circulation that the MJO propagates through.

The dynamical structure and the evolution of cloud morphology within the MJO compares favorably in many respects with other propagating convectively coupled equatorial waves. One implication is that the larger convective envelopes within the Tropics tend to be composed of more shallow convection along their leading edges, a combination of deep convection and stratiform rainfall in their centers, and then a preponderance of stratiform rainfall along their trailing edges, regardless of scale or propagation direction. While this may ultimately be the factor that governs the dynamical similarities across the various wave types, it raises questions about how the smaller-scale, higher-frequency disturbances making up the MJO conspire to produce its heating and dynamical structures. This suggests that the observed cloud morphology is dictated by fundamental interactions with the large-scale circulation.
Reply
Authors: Jochum Markus , Malanotte-Rizzoli Paola
Published: September 2005

A previous study on the generation of equatorial subsurface countercurrents is revisited to clarify some details of the assumptions that are needed to derive the momentum budget. The opportunity is also used to put the study into the context of other previous studies that use quasigeostrophic theory to generalize the transformed Eulerian mean equations.
Anomalies of Meridional Overturning: Mechanisms in the North Atlantic
Authors: Köhl Armin
Published: September 2005

Optimal observations are used to investigate the overturning streamfunction in the North Atlantic at 30°N and 900-m depth. Those observations are designed to impact the meridional overturning circulation (MOC) in numerical models maximally when assimilated and therefore establish the most efficient observation network for studying changes in the MOC. They are also ideally suited for studying the related physical mechanisms in a general circulation model. Optimal observations are evaluated here in the framework of a global 1° model over a 10-yr period. Hydrographic observations useful to monitor the MOC are primarily located along the western boundary north of 30°N and along the eastern boundary south of 30°N. Additional locations are in the Labrador, Irminger, and Iberian Seas. On time scales of less than a year, variations in MOC are mainly wind driven and are made up through changes in Ekman transport and coastal up- and downwelling. Only a small fraction is buoyancy driven and constitutes a slow response, acting on time scales of a few years, to primarily wintertime anomalies in the Labrador and Irminger Seas. Those anomalies are communicated southward along the west coast by internal Kelvin waves at the depth level of Labrador Sea Water. They primarily set the conditions at the northern edge of the MOC anomaly. The southern edge is mainly altered through Rossby waves of the advective type, which originate from temperature and salinity anomalies in the Canary Basin. Those anomalies are amplified on their way westward in the baroclinic unstable region of the subtropical gyre. The exact meridional location of the maximum MOC response is therefore set by the ratio of the strength of these two signals.
Euploidy in somatic cells from R6/2 transgenic Huntington's disease mice
Authors: Petersén Åsa , Stewénius Ylva , Björkqvist Maria , Gisselsson David
Published: September 2005

Background

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a CAG repeat expansion in the HD gene. The huntingtin protein expressed from HD has an unknown function but is suggested to interact with proteins involved in the cell division machinery. The R6/2 transgenic mouse is the most widely used model to study HD. In R6/2 fibroblast cultures, a reduced mitotic index and high frequencies of multiple centrosomes and aneuploid cells have recently been reported. Aneuploidy is normally a feature closely connected to neoplastic disease. To further explore this unexpected aspect of HD, we studied cultures derived from 6- and 12-week-old R6/2 fibroblasts, skeletal muscle cells, and liver cells.

Results

Cytogenetic analyses revealed a high frequency of polyploid cells in cultures from both R6/2 and wild-type mice with the greatest proportions of polyploid cells in cultures derived from skeletal muscle cells of both genotypes. The presence of polyploid cells in skeletal muscle in vivo was confirmed by fluorescence in situ hybridisation with centromeric probes. Enlarged and supernumerary centrosomes were found in cultures from both R6/2 and wild-type mice. However, no aneuploid cells could be found in any of the tissues.

Conclusion

We conclude that polyploid cells are found in fibroblast and skeletal muscle cultures derived from both R6/2 and wild-type littermate mice and that aneuploidy is unlikely to be a hallmark of HD.
Exposure to the field of renal transplantation during undergraduate medical education in the UK
Authors: Edwards Anusha G , Newman Alex , Morgan Justin D
Published: September 2005

Background

There is a lack of surgeons in the field of renal transplantation, with a predicted shortage of over 20 consultants by the year 2005. Early positive exposure to the field, commencing at undergraduate level, has been identified as being vital to improving rates of recruitment. This study was performed to assess the exposure of undergraduates to the field of renal transplantation during medical education in the UK.

Methods

In October 2004 a questionnaire was sent to the clinical deans of all UK medical schools regarding undergraduate exposure to renal transplantation.

Results

Twenty-five replies were received, giving a response rate of 96%. All but one school had a centre for renal transplantation in their region. Three schools (12%) gave no formal lecture or tutorial on the subject during the entire course. Of the remainder, between one to four formal sessions were provided, ranging from 15 minutes to 3 hours duration.

Six medical schools (24%) provided no compulsory clinical exposure to renal transplantation, with a further five (20%) saying that students may receive exposure by chance. The average length of attachment was three weeks. Twenty-one medical schools (84%) provided between 1–10% of students a choice to study renal transplantation, as part of electives and special study modules.

Conclusion

This study reveals a variation between, and within, medical schools in the levels of formal teaching. If the trends in recruitment to renal transplantation are to be reversed, we have an obligation to improve upon the medical education that students currently receive.
Geometrical spreading of P-waves in horizontally layered, azimuthally anisotropic media
Authors: Xu Xiaoxia , Tsvankin Ilya , Pech Andrés
Published: September 2005

For processing and inverting reflection data, it is convenient to represent geometrical spreading through the reflection traveltime measured at the earth's surface. Such expressions are particularly important for azimuthally anisotropic models in which variations of geometrical spreading with both offset and azimuth can significantly distort the results of wide-azimuth amplitude-variation-with-offset (AVO) analysis. Here, we present an equation for relative geometrical spreading in laterally homogeneous, arbitrarily anisotropic media as a simple function of the spatial derivatives of reflection traveltimes. By employing the Tsvankin-Thomsen nonhyperbolic moveout equation, the spreading is represented through the moveout coefficients, which can be estimated from surface seismic data. This formulation is then applied to P-wave reflections in an orthorhombic layer to evaluate the distortions of the geometrical spreading caused by both polar and azimuthal anisotropy. The relative geometrical spreading of P-waves in homogeneous orthorhombic media is controlled by five parameters that are also responsible for time processing. The weak-anisotropy approximation, verified by numerical tests, shows that azimuthal velocity variations contribute significantly to geometrical spreading, and the existing equations for transversely isotropic media with a vertical symmetry axis (VTI) cannot be applied even in the vertical symmetry planes. The shape of the azimuthally varying spreading factor is close to an ellipse for offsets smaller than the reflector depth but becomes more complicated for larger offset-to-depth ratios. The overall magnitude of the azimuthal variation of the geometrical spreading for the moderately anisotropic model used in the tests exceeds 25% for a wide range of offsets. While the methodology developed here is helpful in modeling and analyzing anisotropic geometrical spreading, its main practical application is in correcting the wide-azimuth AVO signature for the influence of the anisotropic overburden.
A new iterative method for computing the magnetic field at high magnetic susceptibilities
Authors: Purss Matthew B. J. , Cull James P.
Published: September 2005

Failure to adequately correct for the effects of self-demagnetization can lead to misinterpretation of magnetic survey data, thereby reducing the success of mineral exploration programs. Numeric methods commonly used to correct for self-demagnetization of finite three-dimensional bodies are restricted to moderate magnetic susceptibilities (χ < 1 SI) because at higher values (χ ≥ 1 SI), the approximation errors for nonellipsoidal bodies become excessive. This paper reports a new method that allows for calculation of the magnetic field from arbitrary finite bodies with high magnetic susceptibility while minimizing approximation errors caused by the use of self-demagnetization corrections for nonellipsoidal bodies. This technique uses a segmented model defined by spherical elements (or voxels) of arbitrary diameter and an iterative computation of the magnetic field at the center of each voxel in free space and then with respect to the surrounding voxels.
Gas hydrates at the Storegga Slide: Constraints from an analysis of multicomponent, wide-angle seismic data
Authors: Bünz Stefan , Mienert Jürgen , Vanneste Maarten , Andreassen Karin
Published: September 2005

Geophysical evidence for gas hydrates is widespread along the northern flank of the Storegga Slide on the mid-Norwegian margin. Bottom-simulating reflectors (BSR) at the base of the gas hydrate stability zone cover an area of approximately 4000 km[Formula: see text], outside but also inside the Storegga Slide scar area. Traveltime inversion and forward modeling of multicomponent wide-angle seismic data result in detailed P- and S-wave velocities of hydrate- and gas-bearing sediment layers. The relationship between the velocities constrains the background velocity model for a hydrate-free, gas-free case. The seismic velocities indicate that hydrate concentrations in the pore space of sediments range between 3% and 6% in a zone that is as much as 50 m thick overlying the BSR. Hydrates are most likely disseminated, neither cementing the sediment matrix nor affecting the stiffness of the matrix noticeably. Average free-gas concentrations beneath the hydrate stability zone are approximately 0.4% to 0.8% of the pore volume, assuming a homogeneous gas distribution. The free-gas zone underneath the BSR is about 80 m thick. Amplitude and reflectivity analyses suggest a rather complex distribution of gas along specific sedimentary strata rather than along the base of the gas hydrate stability zone (BGHS). This gives rise to enhanced reflections that terminate at the BGHS. The stratigraphic control on gas distribution forces the gas concentration to increase slightly with depth at certain locations. Gas-bearing layers can be as thin as 2 m.
High-resolution wave-equation AVA imaging: Algorithm and tests with a data set from the Western Canadian Sedimentary Basin
Authors: Wang Juefu , Kuehl Henning , Sacchi Mauricio D.
Published: September 2005

This paper presents a 3D least-squares wave-equation migration method that yields regularized common-image gathers (CIGs) for amplitude-versus-angle (AVA) analysis. In least-squares migration, we pose seismic imaging as a linear inverse problem; this provides at least two advantages. First, we are able to incorporate model-space weighting operators that improve the amplitude fidelity of CIGs. Second, the influence of improperly sampled data (footprint noise) can be diminished by incorporating data-space weighting operators. To investigate the viability of this class of methods for oil and gas exploration, we test the algorithm with a real-data example from the Western Canadian Sedimentary Basin. To make our problem computationally feasible, we utilize the 3D common-azimuth approximation in the migration algorithm. The inversion algorithm uses the method of conjugate gradients with the addition of a ray-parameter-dependent smoothing constraint that minimizes sampling and aperture artifacts. We show that more robust AVA attributes can be obtained by properly selecting the model and data-space regularization operators. The algorithm is implemented in conjunction with a preconditioning strategy to accelerate convergence. Posing the migration problem as an inverse problem leads to enhanced event continuity in CIGs and, hence, more reliable AVA estimates. The vertical resolution of the inverted image also improves as a consequence of increased coherence in CIGs and, in addition, by implicitly introducing migration deconvolution in the inversion.
Expression and Functional Assessment of an Alternatively Spliced Extracellular Ca2+-Sensing Receptor in Growth Plate Chondrocytes
Authors: Rodriguez Luis , Tu Chialing , Cheng Zhiqiang , Chen Tsui-Hua , Bikle Daniel , Shoback Dolores , Chang Wenhan
Published: September 2005

The extracellular Ca2+-sensing receptor (CaR) plays an essential role in mineral homeostasis. Studies to generate CaR-knockout (CaR−/−) mice indicate that insertion of a neomycin cassette into exon 5 of the mouse CaR gene blocks the expression of full-length CaRs. This strategy, however, allows for the expression of alternatively spliced CaRs missing exon 5 [Exon5(−)CaRs]. These experiments addressed whether growth plate chondrocytes (GPCs) from CaR−/− mice express Exon5(−)CaRs and whether these receptors activate signaling. RT-PCR and immunocytochemistry confirmed the expression of Exon5(−)CaR in growth plates from CaR−/− mice. In Chinese hamster ovary or human embryonic kidney-293 cells, recombinant human Exon5(−)CaRs failed to activate phospholipase C likely due to their inability to reach the cell surface as assessed by intact-cell ELISA and immunocytochemistry. Human Exon5(−)CaRs, however, trafficked normally to the cell surface when overexpressed in wild-type or CaR−/− GPCs. Immunocytochemistry of growth plate sections and cultured GPCs from CaR−/− mice showed easily detectable cell-membrane expression of endogenous CaRs (presumably Exon5(−)CaRs), suggesting that trafficking of this receptor form to the membrane can occur in GPCs. In GPCs from CaR−/− mice, high extracellular [Ca2+] ([Ca2+]e) increased inositol phosphate production with a potency comparable with that of wild-type GPCs. Raising [Ca2+]e also promoted the differentiation of CaR−/− GPCs as indicated by changes in proteoglycan accumulation, mineral deposition, and matrix gene expression. Taken together, our data support the idea that expression of Exon5(−)CaRs may compensate for the loss of full-length CaRs and be responsible for sensing changes in [Ca2+]e in GPCs in CaR−/− mice.
Reduced Anorexigenic Efficacy of Leptin, But Not of the Melanocortin Receptor Agonist Melanotan-II, Predicts Diet-Induced Obesity in Rats
Authors: van Dijk Gertjan , de Vries Koert , Nyakas Csaba , Buwalda Bauke , Adage Tiziana , Kuipers Folkert , Kas Martien J. H. , Adan Roger A. H. , Wilkinson Charles W. , Thiele Todd E. , Scheurink Anton J. W.
Published: September 2005

Leptin gains access to the central nervous system where it influences activity of neuronal networks involved in ingestive behavior, neuroendocrine activity, and metabolism. In particular, the brain melanocortin (MC) system is important in leptin signaling and maintenance of energy balance. Although leptin or MC receptor insensitivity has been proposed to be associated with obesity, the present study compared central leptin and MC receptor stimulation on some of the above-mentioned parameters and investigated whether these treatments predict proneness to diet-induced obesity (DIO) in outbred Wistar rats. Third-cerebroventricular administration of equi-anorexigenic doses of leptin and of the MC agonist melanotan-II caused comparable increases in plasma ACTH and corticosterone levels and c-Fos-labeling in approximately 70% of paraventricular hypothalamic (PVN) neuronal cell bodies containing CRH. This reinforces involvement of paraventricular CRH neurons in the short-term neuroendocrine and ingestive effects of leptin and melanocortins. In the DIO prediction study, anorexigenic efficacy of melanotan-II was not correlated with any parameter linked to DIO but was highly correlated with MC in situ binding (with labeled [Nle4,d-Phe7]α-MSH) as well as CRH immunoreactivity in the PVN of DIO rats. This suggests intricate relationships among MC signaling, the CRH system, and ingestive behavior unrelated to DIO. In the same animals, leptin’s anorexigenic efficacy was not correlated with PVN MC in situ binding or CRH immunoreactivity but correlated inversely to post-DIO plasma leptin, liver weight, and abdominal adiposity, the latter being correlated to insulin resistance. Thus, differences in leptin but not MC signaling might underlie DIO, visceral obesity, and insulin resistance.
Expression of Androgen and Estrogen Receptors in Sertoli Cells: Studies Using the Mouse SK11 Cell Line
Authors: Sneddon Sharon F. , Walther Norbert , Saunders Philippa T. K.
Published: September 2005

Sertoli cells (Sc) play a major role in the establishment and maintenance of spermatogenesis. In the adult testis, Sc contain androgen receptor (AR) and estrogen receptor (ER)-β but exhibit a loss of steroid responsiveness when maintained in primary culture. In the present study, we demonstrated that a transformed murine cell line (SK11) has retained a Sc phenotype and remains steroid responsive. SK11 cells expressed mRNAs found in Sc (aromatase, sulfated glycoprotein-1, sulfated glycoprotein-2, GATA-1, Sry-type high-mobility-group box transcription factor-9, testatin, dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1) including those for AR and ERβ but not ERα. AR and ERβ were immunolocalized to cell nuclei, and their ability to activate gene expression was investigated using transient transfections with reporter constructs containing either 3xERE or pem-androgen-responsive element promoters. Expression of the 3xERE reporter was induced after incubation with 17β-estradiol (E2), 5α-androstane-3-β, 17β-diol (3βAdiol), or testosterone (T); up-regulation of the pem-androgen-responsive element reporter was detected only in the presence of T or dihydrotestosterone. Activation of the ERE reporter did not occur after targeted knockdown of ERβ mRNA. Expression of AR and ERβ mRNAs was increased after incubation of cells with T or E2, respectively. In conclusion, we have demonstrated that the SK11 Sc cell line contains functional AR and ERβ and that treatment of the cells with their respective steroids results in an increase in the amount of their mRNAs. Our results suggest that E2 or 3βAdiol acting via ERβ might modulate Sc function in vivo and that SK11 cells provide a useful model that can be used to complement studies using Sc selective gene ablation.
Regulation of focal adhesion dynamics and disassembly by phosphorylation of FAK at tyrosine 397
Authors: Hamadi Abdelkader , Bouali Maya , Dontenwill Monique , Stoeckel Herrade , Takeda Kenneth , Rondé Philippe
Published: September 2005

One of the major tyrosine phosphorylation activities linked to integrin signalling is that of focal adhesion kinase (FAK). High amounts of FAK are located at specialised subcellular compartments known as focal adhesions. FAK tyrosine phosphorylation at focal adhesions is increased by various stimuli including integrin engagement during migration processes, growth factors and oncogene transformation. Phosphorylation of FAK at various tyrosine residues regulates focal adhesion turnover by mechanisms that are not well understood. We made a fluorescent FAK mutant (Y397F-FAK/YCam) to analyse, in living cells, how phosphorylation of FAK regulates the turnover of focal adhesions. We found that expression of Y397F-FAK/YCam in human astrocytoma cells decreases the level of phosphorylation of FAK at endogenous Tyr-397 residues and at both endogenous and exogenous Tyr-576 residues, in the putative activation loop of the kinase. This corresponds to a decrease in phosphorylation of FAK at focal adhesions in Y397F-FAK/YCam cells, since the cellular localisation of FAK phosphoTyr-576 in cells expressing Y397F-FAK/YCam or FAK/YCam was not different. Furthermore, FRAP analysis showed that phosphorylation of FAK at Tyr-397 increases specifically the time-residency of FAK at focal adhesions but not in cytosol. This in turn induces disassembly of focal adhesions at the cell tail and promotes cell motility as shown by the decrease in microtubule-mediated turnover of Y397F-FAK/YCam-containing focal adhesions. Our data show that phosphorylation of FAK at Tyr-397 is a key determinant of how FAK controls focal adhesion turnover.
Stroke volume and cardiac output in juvenile elephant seals during forced dives
Authors: Thornton Sheila J. , Hochachka Peter W. , Crocker Daniel E. , Costa Daniel P. , LeBoeuf Burney J. , Spielman Daniel M. , Pelc Norbert J.
Published: September 2005

The aim of this study was to examine the effect of forced diving on cardiac dynamics in a diving mammal by evaluating cardiac output and heart rate. We used MR Imaging and phase contrast flow analysis to obtain accurate flow measurements from the base of the aorta. Heart rate (fh)and cardiac output (Q̇) were measured before, during and after dives in four restrained juvenile northern elephant seals, Mirounga angustirostris, and stroke volume(Vs) was calculated(Vs=Q̇/fh). Mean Q̇ during diving (4011±387 ml min-1) and resting (6530±1018 ml min-1) was not significantly different (paired t-test; P<0.055). Diving was accompanied by a 20% increase in Vs over the pre-dive level. Pre-dive, post-dive or diving fh was not significantly correlated with Vs during any state. Diving Vs correlated negatively with the bradycardic ratio(diving fh to pre-dive fh). In this study, the degree of bradycardia during diving was less than in previous pinniped studies, suggesting that the reduction in vagal input may contribute to the observed increase in Vs.
Prior classical olfactory conditioning improves odour-cued flight orientation of honey bees in a wind tunnel
Authors: Chaffiol Antoine , Laloi David , Pham-Delègue Minh-Hà
Published: September 2005

Odours are key cues used by the honey bee in various situations. They play an important role in sexual attraction, social behaviour and location of profitable food sources. Here, we were interested in the role of odours in orientation at short distance, for instance the approach flight to a floral patch or in close proximity to the hive entrance. Using a newly designed wind tunnel, we investigated the orientation behaviour of the bee towards two different odours: a social odour and a floral component, linalool. We then tested the effect of prior olfactory conditioning (conditioning of the proboscis extension reflex) on subsequent flight orientation. We showed that both stimuli induced orientated behaviour (orientated flights, circling around the odour source) in up to 70% of the worker bees, social odour being slightly more attractive than the linalool. We found thereafter that orientation performance towards the floral compound can be significantly enhanced by prior classical olfactory learning. This type of information transfer, from a Pavlovian associative context to an orientation task, might allow future foragers to acquire, within the hive, relevant information about the odours and food they will encounter during their later foraging bouts.
Feeding kinematics ofKogiaandTursiops(Odontoceti:Cetacea): characterization of suction and ram feeding
Authors: Bloodworth Brian , Marshall Christopher D.
Published: September 2005

The feeding kinematics of dwarf and pygmy sperm whales (Kogia simaand K. breviceps) and bottlenose dolphins Tursiops truncatuswere characterized and compared incorporating the Ram-Suction Index (RSI). Mean RSI data support a suction feeding strategy for Kogia(-0.67±0.29; mean ± s.d.) and a ram feeding strategy for Tursiops (0.94±0.11; mean ± s.d.). Tursiops displayed two ram-based feeding behaviours: open gape approach, where gape was at least 50% of maximum in the first video field, and closed gape approach, where gape increased near food items. Four feeding phases were identified in both odontocetes: preparatory, jaw opening, gular depression and jaw closing. The mean Kogia feeding cycle duration(470±139 ms) was significantly shorter (P<0.003) than all Tursiops groups (pooled: 863±337 ms; open gape approach:1211±207 ms; closed gape approach: 662±207 ms). Kogiamean maximum gape angle (39.8±18.9°), mean maximum opening and closing gape angle velocities (293±261 deg. s-1 and 223±121 deg. s-1, respectively) were significantly greater(P<0.005) than pooled Tursiops mean maximum gape angle(24.8±6.6°), mean maximum opening and closing gape angle velocities(84±56 deg. s-1 and 120±54 deg. s-1,respectively). Negative Kogia RSI values were correlated with increasing maximum gular depression and retraction, wide gape angle, and rapid opening gape angle velocity. Kinematic data support functional hypotheses that odontocetes generate suction by rapid depression of the hyoid and tongue.
Integration of hydrodynamic and odorant inputs by local interneurons of the crayfish deutocerebrum
Authors: Mellon DeForest
Published: September 2005

Intracellular electrodes were used to record from local interneurons in the olfactory lobes of the midbrain in the crayfish Procambarus clarkii.Cells that resembled previously studied central targets of olfactory receptor neurons on the lateral antennular flagellum were specifically examined for their responses to hydrodynamic stimuli. Initiation of water movement past the antennular flagellum, confined within an olfactometer, evoked a triphasic excitatory-inhibitory-excitatory postsynaptic potential lasting up to 2 s that generated spikes on depolarizing phases of the response sequence. Odorant pulses seamlessly imbedded in the water pulse past the antennule evoked purely excitatory, dose-dependent postsynaptic responses and associated spike trains. The latency of the initial phase of the response to water was approximately half as long as the latency of the response to odorant, suggesting that different afferent pathways are involved in responses to hydrodynamic and odorant stimuli, respectively. In some olfactory lobe interneurons that resembled previously described cells classified as Type I, conjoint stimulation of fluid onset and odorant evoked responses that were twice the amplitude of the summed response to either hydrodynamic or odorant stimulation alone, suggesting that the olfactory responses were potentiated by hydrodynamic input. Individuals of at least one other class of first-order interneuron that responded to both hydrodynamic and odorant stimulation were occasionally recorded from. These results indicate that multimodal integration of chemical and mechanical information occurs at the level of first-order sensory interneurons in the crayfish brain.
Nestlé Improves Its Financial Reporting with Management Science
Authors: Oggier Christophe , Fragnière Emmanuel , Stuby Jeremy
Published: September 2005

Nestlé’s executive information system (EIS) department gathers data from the firm’s subsidiaries (reporting units) to provide top management with operational, financial, and strategic information. In 1996, the EIS department decided to improve its service by using business analytics tools based on management science (MS) techniques. It wanted to encourage analysts and controllers to make better use of the information supplied. We developed four OR modules: sensitivity analysis, forecasting, simulation, and optimization, and integrated them into a more global modeling scheme for evaluating the economic profitability of Nestlé’s projects and more generally evaluating the value of the Nestlé group and its multifocal businesses. Disseminating this approach within the Nestlé group through training and internal consulting has been a long and important process that has increased the number of managers accustomed to quantitative decision making and established new reporting protocols imposing the use of MS models.
A Note on the Optimal EOQ for Announced Price Increases in the Infinite Horizon
Authors: Lim Andrew , Rodrigues Brian
Published: September 2005

Huang et al. (2003) used the Cesaro limit of a savings function to determine the optimal special order in an EOQ model with single announced price increases over an infinite horizon. In this note, we point out that the savings function is not Cesaro summable. More importantly, no limiting argument for the cost function d(t, Qs) as t→∞ is necessary at all given that this function is periodic for which it suffices to optimize the integral of the function over any given period.
Staggering Periodic Replenishment in Multivendor JIT Environments
Authors: Hum Sin-Hoon , Sharafali Moosa , Teo Chung-Piaw
Published: September 2005

The delivery scheduling problem studied in this paper was motivated by the operation in a large personal computer assembly plant, which was using multisourcing for some of its materials. The company’s objective was to design a delivery schedule so that the average inventory level in the factory was minimized. We show that the problem is intimately related to a classical inventory staggering problem, where the focus is on the computation of the peak inventory level associated with the replenishment policy. This connection allows us to show that the delivery scheduling problem is NP-hard. For the two-vendor case with integral replenishment intervals, we propose a generalized form of Homer’s scheduling heuristic and obtain performance bounds for the classical inventory staggering problem. Our analysis uses the Chinese remainder theorem in an interesting way. The approach can be generalized to the case with more than two vendors, leading to a strong linear-programming-based lower bound for the inventory staggering problem. We illustrate this technique for the case in which all the replenishment intervals are relatively prime, establishing a bound that is not greater than 140% of the optimal. We examine the implications of these results to the delivery scheduling problem.
Reducing Adverse Selection through Customer Relationship Management
Authors: Cao Yong , Gruca Thomas S.
Published: September 2005

Adverse selection is an important problem for marketers. To reduce the chances of acquiring an unprofitable customer, companies may screen prospects who respond to a marketing offer. Prospects who respond are often not approved. At the same time, prospects who are likely to be approved are unlikely to respond to a given marketing offer. Using data from a firm's customer relationship management system, the authors show how to target prospects who are likely to respond and be approved. This approach increases the number of customers who are approved and reduces the number of applicants who may defect after being turned down. This method can be extended to new customer acquisition and more effective targeting of costly promotions to migrate customers to higher levels of lifetime value.
Reference Price Research: Review and Propositions
Authors: Mazumdar Tridib , Raj S.P. , Sinha Indrajit
Published: September 2005

A substantial body of research evidence has now accumulated in the reference price literature. One stream of research has identified the antecedents of reference price and has assessed their effects through experimentation. Others have calibrated a variety of reference price models on panel data and reported the effects on brand choice and other purchase decisions. In this article, the authors review the published literature on reference price in both the behavioral and modeling streams. They offer an integrative framework to review prior research on (1) the formation of reference price, (2) retrieval and use of reference price, and (3) influences of reference price on various purchase decisions and evaluations. In doing so, the authors examine the influences of consumers' prior purchase history and contextual moderators, such as specific purchase occasions, promotional environment of the store, and product category characteristics. They summarize the key findings, identify the unresolved issues, and offer an agenda for further research, which includes a set of testable propositions. They also identify the methodological challenges that face reference price research. In the concluding section, the authors discuss the managerial implications of reference price research.
Enhancement of Excitatory Synaptic Integration by GABAergic Inhibition in the Subthalamic Nucleus
Authors: Baufreton Jérôme , Atherton Jeremy F. , Surmeier D. James , Bevan Mark D.
Published: September 2005

The activity patterns of subthalamic nucleus (STN) neurons, which are intimately related to normal movement and abnormal movement in Parkinson's disease (PD), are sculpted by feedback GABAergic inhibition from the reciprocally connected globus pallidus (GP). To understand the principles underlying the integration of GABAergic inputs, we used gramicidin-based patch-clamp recording of STN neurons in rat brain slices. Voltage-dependent Na+(Nav) channels actively truncated synthetic IPSPs and were required for autonomous activity. In contrast, hyperpolarization-activated cyclic nucleotide-gated and class 3 voltage-dependent Ca2+channels contributed minimally to the integration of single or low-frequency trains of IPSPs and autonomous activity. Interestingly, IPSPs modified action potentials (APs) in a manner that suggested IPSPs enhanced postsynaptic Navchannel availability. This possibility was confirmed in acutely isolated STN neurons using current-clamp recordings containing IPSPs as voltage-clamp waveforms. Tetrodotoxin-sensitive subthreshold and spike-associated Na+currents declined during autonomous spiking but were indeed transiently boosted after IPSPs. A functional consequence of inhibition-dependent augmentation of postsynaptic excitability was that EPSP–AP coupling was dramatically improved when IPSPs preceded EPSPs.

Because STN neuronal activity exhibits coherence with cortical β-oscillations in PD, we tested how rhythmic sequences of cortical EPSPs were integrated in the absence and presence of feedback inhibition. STN neuronal activity was consistently entrained by EPSPs only in the presence of feedback inhibition. These observations suggest that feedback inhibition from the GP is critical for the emergence of coherent β-oscillations between the cortex and STN in PD.
20-Oxo-5β-Pregnan-3α-yl Sulfate Is a Use-Dependent NMDA Receptor Inhibitor
Authors: Petrovic Milos , Sedlacek Miloslav , Horak Martin , Chodounska Hana , Vyklický Ladislav
Published: September 2005

NMDA receptors are ligand-gated ion channels permeable to calcium and play a critical role in excitatory synaptic transmission, synaptic plasticity, and excitotoxicity. They are heteromeric complexes of NR1 combined with NR2A-D and/or NR3A-B subunits that are activated by glutamate and glycine and whose activity is modulated by allosteric modulators. In this study, patch-clamp recordings from human embryonic kidney 293 cells expressing NR1/NR2 receptors were used to study the molecular mechanism of the endogenous neurosteroid 20-oxo-5β-pregnan-3α-yl sulfate (3α5βS) action at NMDA receptors. 3α5βS was a twofold more potent inhibitor of responses mediated by NR1/NR2C-D receptors than those mediated by NR1/NR2A-B receptors. The structure of the extracellular loop between the third and fourth transmembrane domains of the NR2 subunit was found to be critical for the neurosteroid inhibitory effect. The degree of 3α5βS-induced inhibition of responses to glutamate was voltage independent, with recovery lasting several seconds. In contrast, application of 3α5βS in the absence of agonist had no effect on the subsequent response to glutamate made in the absence of the neurosteroid. A kinetic model was developed to explain the use-dependent action of 3α5βS at NMDA receptors. In accordance with the model, 3α5βS was a less potent inhibitor of NMDA receptor-mediated EPSCs and responses induced by a short application of 1 mmglutamate than of those induced by a long application of glutamate.

These results suggest that 3α5βS is a use-dependent but voltage-independent inhibitor of NMDA receptors, with more potent action at tonically than at phasically activated receptors. This may be important in the treatment of excitotoxicity-induced neurodegeneration.