bluuebunny/crossref_metadata_2025 huggingface dataset:
SUPERSYMMETRIC WZW σ MODEL ON INFINITE AND HALF-PLANE
Authors: ZAIT R. A. , MOURAD M. F.
Published: July 2005

We study classical integrability of the supersymmetric U(N) σ model with the Wess–Zumino–Witten term on infinite and half-plane. We demonstrate the existence of nonlocal conserved currents of the model and derive general recursion relations for the infinite number of the corresponding charges in a superfield framework. The explicit forms of the first few supersymmetric charges are constructed. We show that the considered model is integrable on infinite plane as a consequence of the conservation of the supersymmetric charges. Also, we study the model on half-plane with free boundary, and examine the conservation of the supersymmetric charges on half-plane and find that they are conserved as a result of the equations of motion and the free boundary condition. As a result, the model on half-plane with free boundary is integrable. Finally, we conclude the paper and some features and comments are presented.
CRITICAL PARAMETERS OF PHASE TRANSITION IN DUAL QCD
Authors: CHANDOLA H. C. , YADAV DINESH , PANDEY H. C. , DEHNEN H.
Published: July 2005

Color confinement is studied in dual version of SU (2) color gauge theory using its topological structure and the dynamical breaking of the magnetic symmetry which has been shown to effectively trigger the QCD monopole condensation in a dynamical way. The resulting flux tube structure of the QCD vacuum is explored which has been shown to lead to the perfect dual superconducting nature to the QCD vacuum in its dynamically broken phase. The analysis of the flux tube energy at different hadronic length scales has been shown to lead to the appearance of the strong confinement forces in QCD vacuum at large hadronic distances and an indication for the deconfinement phase at small scales. The analysis of the flux tube energy is then used to compute numerically the critical radius and the critical flux tube density of the phase transition from the flux tube phase to deconfined one inside hadrons. The numerical estimates are shown to be in fairly good agreement with the analytical values. The possible implications of these critical parameters on the formation of QGP as a result of the flux tubes fusion in intermediate energy regime are also discussed.
A GLOBAL TEST OF FACTORIZATION FOR NUCLEON–NUCLEON, γp AND γγ SCATTERING
Authors: BLOCK MARTIN M. , KANG KYUNGSIK
Published: July 2005

The purpose of this paper is to show that the cross-section factorization relation σnn(s)/σγp(s) = σγp(s)/σγγ(s) is satisfied experimentally in the energy domain [Formula: see text], where the σ's are total cross-sections and nn denotes the even portion of the pp and [Formula: see text] total cross-section. A convenient phenomenological parametrization for a global simultaneous fit to the pp, [Formula: see text], γp and γγ total cross-section data together with the ρ-value data for pp and [Formula: see text] is provided by using real analytic amplitudes. Within experimental errors, we show that factorization is satisfied when we unfold the published γγ data which had averaged the cross-sections obtained by using the two different PHOJET and PYTHIA Monte Carlo results. Our analysis clearly favors the PHOJET results and suggests that the additive quark model, together with vector meson dominance, allows one to compute σγp(s) and σγγ(s) from σnn(s) with essentially no free parameters. The universal ρ-value predicted by our fit, i.e. ρnn = ργp = ργγ, is compared to the ρ-value obtained by a QCD-inspired analysis of [Formula: see text] and pp data, including the p-air cross-sections from cosmic rays. The ρ-values obtained from the two techniques are essentially indistinguishable in the energy region [Formula: see text], giving us increased confidence in our parametrization of the cross-sections needed for the factorization relation.
DISTRIBUTION OF ESCAPE TIMES OVER A FLUCTUATING BARRIER IN A MECHANICAL SYSTEM
Authors: DE ALCANTARA BONFIM O. F. , MAE GOIN JENNIFER , ASAY JOHN
Published: July 2005

We consider the problem of transitions between states of a bistable mechanical system induced by a harmonically, and a randomly oscillating barrier. We study the problem both experimentally and numerically. The system consists of a mass attached to a rotating disk, nonlinearly coupled to a spring subject to an external force. For periodically driven external forces, the transition rate across the barrier increases linearly with the frequency of the driving force until the system reaches the boundary of a chaotic region. Beyond this boundary, the rate drops sharply until it is fully suppressed at the end of this region. When the driving force is stochastic we find that the transition rate also has a maximum, and that its position depends on the rate of switching of the random force.
THE PATH TOWARDS A LONGER LIFE: ON INVARIANT SETS AND THE ESCAPE TIME LANDSCAPE
Authors: BOLLT ERIK M.
Published: July 2005

Unstable invariant sets are important to understand mechanisms behind many dynamically important phenomenon such as chaotic transients which can be physically relevant in experiments. However, unstable invariant sets are nontrivial to find computationally. Previous techniques such as the PIM triple method [Nusse & Yorke, 1989] and simplex method variant [Moresco & Dawson, 1999], and even the step-and-stagger method [Sweet et al., 2001] have computationally inherent dimension limitations. In the current study, we explicitly investigate the landscape of an invariant set, which leads us to a simple gradient search algorithm to construct points close to the invariant set. While the calculation of the necessary derivatives can be computationally very expensive, the methods of our algorithm are not as dimension dependant as the previous techniques, as we show by examples such as the two-dimensional instability example from [Sweet et al., 2001] followed by a four-dimensional instability example, and then a nine-dimensional flow from the Yoshida equations, with a two-dimensional instability.
INHERENT GLOBAL STABILIZATION OF UNSTABLE LOCAL BEHAVIOR IN COUPLED MAP LATTICES
Authors: ATMANSPACHER HARALD , SCHEINGRABER HERBERT
Published: July 2005

The behavior of two-dimensional coupled map lattices is studied with respect to the global stabilization of unstable local fixed points without external control. It is numerically shown under which circumstances such inherent global stabilization can be achieved for both synchronous and asynchronous updating. Two necessary conditions for inherent global stabilization are derived analytically.
CHAOS IN A THREE-DIMENSIONAL VOLTERRA–GAUSE MODEL OF PREDATOR–PREY TYPE
Authors: GINOUX JEAN-MARC , ROSSETTO BRUNO , JAMET JEAN-LOUIS
Published: July 2005

The aim of this paper is to present results concerning a three-dimensional model including a prey, a predator and top-predator, which we have named the Volterra–Gause model because it combines the original model of V. Volterra incorporating a logisitic limitation of the P. F. Verhulst type on growth of the prey and a limitation of the G. F. Gause type on the intensity of predation of the predator on the prey and of the top-predator on the predator. This study highlights that this model has several Hopf bifurcations and a period-doubling cascade generating a snail shell-shaped chaotic attractor.

With the aim of facilitating the choice of the simplest and most consistent model a comparison is established between this model and the so-called Rosenzweig–MacArthur and Hastings–Powell models. Many resemblances and differences are highlighted and could be used by the modellers.

The exact values of the parameters of the Hopf bifurcation are provided for each model as well as the values of the parameters making it possible to carry out the transition from a typical phase portrait characterizing one model to another (Rosenzweig–MacArthur to Hastings–Powell and vice versa).

The equations of the Volterra–Gause model cannot be derived from those of the other models, but this study shows similarities between the three models. In cases in which the top-predator has no effect on the predator and consequently on the prey, the models can be reduced to two dimensions. Under certain conditions, these models present slow–fast dynamics and their attractors are lying on a slow manifold surface, the equation of which is given.
BIFURCATIONS IN DC–DC SWITCHING CONVERTERS: REVIEW OF METHODS AND APPLICATIONS
Authors: EL AROUDI A. , DEBBAT M. , GIRAL R. , OLIVAR G. , BENADERO L. , TORIBIO E.
Published: July 2005

This paper presents, in a tutorial manner, nonlinear phenomena such as bifurcations and chaotic behavior in DC–DC switching converters. Our purpose is to present the different modeling approaches, the main results found in the last years and some possible practical applications. A comparison of the different models is given and their accuracy in predicting nonlinear behavior is discussed. A general Poincaré map is considered to model any multiple configuration of DC–DC switching converters and its Jacobian matrix is derived for stability analysis. More emphasis is done in the discrete-time approach as it gives more accurate prediction of bifurcations. The results are reproduced for different examples of DC–DC switching converters studied in the literature. Some methods of controlling bifurcations are applied to stabilize Unstable Periodic Orbits (UPOs) embedded in the dynamics of the system. Statistical analysis of these systems working in the chaotic regime is discussed. An extensive list of references is included.
FAST BISTATIC SIGNAL-TO-REVERBERATION-RATIO CALCULATION
Authors: HARRISON CHRIS H.
Published: July 2005

Closed-form expressions are presented for signal and reverberation in a wide variety of bistatic scenarios including variable bottom bathymetry. These extend the findings and inferences from already published expressions for monostatic sonar and provide considerable insight into sonar performance. They are also developed into a hybrid numerical solution that can be applied to realistic grided environments (though isovelocity so far). Derivations are based on an eigenray sum with (bistatically varying) Lambert's law scattering, and the result is valid for general smoothly varying bathymetry. Examples of reverberation, target echo, and signal-to-reverberation-ratio (SRR) are given for the case of a uniformly sloping bottom abutting a shelf. The SRR is always high immediately behind the receiver (i.e. in the opposite direction from the bistatic source). Conversely the SRR is very poor between the source and receiver. An example of the hybrid numerical approach with realistic bathymetry from the area in between Sicily and Malta shows that Lambert's law with "mode-stripping" lead to high detection ranges. Noise limiting moderates this and there is then a roughly elliptical annular region with high SRR; inside and outside the annulus performance is poor. Calculating a full set of plots takes only a few seconds on a PC and requires no priming or tabulation. Therefore sonar assessment of complete moving scenarios becomes a practical proposition.
RISK ASSESSMENT OF SEAFLOOR WASTE: ACOUSTICAL IMAGING OF BURIED WASTE
Authors: CAITI ANDREA , PALMESE MARIA , TRUCCO ANDREA
Published: July 2005

This work describes some of the ongoing activities in the framework of the EU-sponsored project SITAR aimed at developing acoustic methods for imaging of waste barrels/containers of small dimension buried in unconsolidated sea sediments. In particular, the work relies on acoustic sub-bottom scattering measurement techniques, with adaptive geometrical configuration of the transmitting/receiving system. The approach ultimately leads to a full 3D measurement of the acoustic scattered field, including bottom and sub-bottom effects, plus the scattering due to buried objects in the scene. The 3D dense acoustic image is then processed in order to automatically extract relevant object(s) features, as size, 3D orientation, impedance contrast; this is obtained through a sequence of processing steps including filtering, enhancement, restoration and image segmentation. Preliminary results obtained with simulative data are presented: data are obtained by modeling the surfaces of both seabed and object(s) as a dense, random grid of discrete scatterers, following the Rayleigh reflection coefficient, and integrating the response of the scatterers. The effects due to absorption and refraction moving from water to sediments are also considered. Sediment volume inhomogeneities are modeled by a random distribution of small asymmetric scattering volumes, characterized by their 3D dimensions, density, and reflection coefficient. A volume growing segmentation approach has been applied, showing efficient segmentation capabilities, and robustness to uncertainty.
Nonviral gene transfer to skeletal, smooth, and cardiac muscle in living animals
Authors: Dean David A.
Published: July 2005

The study of muscle physiology has undergone many changes over the past 25 years and has moved from purely physiological studies to those intimately intertwined with molecular and cell biological questions. To ask these questions, it is necessary to be able to transfer genetic reagents to cells both in culture and, ultimately, in living animals. Over the past 10 years, a number of different chemical and physical approaches have been developed to transfect living skeletal, smooth, and cardiac muscle systems with varying success and efficiency. This review provides a survey of these methods and describes some more recent developments in the field of in vivo gene transfer to these various muscle types. Both gene delivery for overexpression of desired gene products and delivery of nucleic acids for downregulation of specific genes and their products are discussed to aid the physiologist, cell biologist, and molecular biologist in their studies on whole animal biology.
Uteroplacental insufficiency alters hepatic expression, phosphorylation, and activity of the glucocorticoid receptor in fetal IUGR rats
Authors: Baserga Mariana , Hale Merica A. , McKnight Robert A. , Yu Xing , Callaway Christopher W. , Lane Robert H.
Published: July 2005

Uteroplacental insufficiency (UPI) induces persistent changes in hepatic gene expression secondary to altered chromatin dynamics in the intrauterine growth- restricted (IUGR) rat liver. The glucocorticoid receptor (GR) is a transcription factor that when activated can induce changes in chromatin structure. To begin the process of identifying pathways by which IUGR affects chromatin structure, we hypothesized that UPI in the rat induces a significant increase in endogenous glucocorticoids (corticosterone) and increases GR expression and activation. To prove our hypothesis, we induced IUGR through bilateral uterine artery ligation of the pregnant rat. At day 1, UPI significantly increased corticosterone levels and was associated with increased total GR mRNA and protein levels in the liver, as well as increased hepatic phosphorylation of GR serine 211. Moreover, cyclin-dependent kinase 2 (CDK2) cyclinA/CDK2 protein levels, which selectively phosphorylate GR serine 211, were also significantly increased. To assess activity of the GR, we measured protein levels of the transcription factor p53 whose levels are downregulated, at least in part, by active GR. In this study, UPI decreased p53 protein and its downstream target Bax mRNA levels. We conclude that UPI in rats affects GR expression and activity in the liver. We speculate that these alterations early in life may contribute to the changes in chromatin structure and gene expression previously described in the IUGR liver.
Perceptions of Compatibility Between Christianity and Judaism in Pauline Interpretation
Authors: Campbell William
Published: July 2005

Contemporary interpretation of Paul is heir to a tradition of Paulinism in which Paul's gospel is almost universally viewed as being in opposition to Judaism. Even the advent of the New Perspective on Paul has not yet succeeded in convincing the majority of scholars that there is no basic incompatibility between Paul and Judaism. One reason for a negative response to the New Perspective is that the acceptance of this viewpoint seems (necessarily) to imply that the great Reformers were somewhat deficient in their understanding of Paul. Their own basic principle of 'reformed and always being reformed' demands, however, a critique of all traditions, including this one. Moreover, inasmuch as modern Pauline scholarship is dependent upon the 19th century invention of the theory of legalism as a pejorative description of Jewish religion, there is a resultant failure to view the Judaism that nurtured Paul, and in which he was continuously in dialogue, other than apologetically or polemically. This is because Christian Pauline interpretation tends to involve a concern for self-understanding and identity that necessarily differentiates the modern agenda from that of Paul, since this concern springs from Enlightenment categories and is therefore foreign to the Apostle. It is the contention of this essay that Paul's letters demonstrate that he was no sectarian, vilifying Judaism for the promotion of a new religion. Since Paul's identity, even after his vision of Christ, remained distinctly Jewish, scholars cannot justifiably use Judaism as a negative foil for Christian self-understanding. Christian faith as such demands neither the denigration of Judaism nor the subversion of Pauline theology into a subjective search for identity.
Apostle to the Gentiles: Constructions of Paul's Identity
Authors: Johnson Hodge Caroline
Published: July 2005

In Galatians 2:7–9, Paul lays out the parameters for the spread of the gospel for himself and his Judiean colleagues: all agreed that ?We should go to the gentiles and they to the circumcised? (Gal 2:9). This division of labor is crucial for understanding Paul: his task involves an intentional crossing of ethnic boundaries. Ethnicity determined the organization of the mission and Paul was responsible for the ethnic and religious "other."Here I explore Paul's construction of his identity as a Judean teacher of gentiles. Drawing on recent work in anthropology and critical race theory, I propose an approach which understands identity as flexible and multiplicative. Two principles operate within this dynamic model: 1) people shift identities according to specific circumstances and 2) people prioritize their various identities, ranking some higher than others.This model helps us understand Paul, who describes himself in a variety of ways: Judean by birth, born of the tribe of Benjamin, seed of Abraham, apostle to the gentiles, in Christ. These multiple identities as Paul shifts among them and sometimes ranks one over others serve his argument in strategic ways. He is willing, for example, to forego certain practices of the law (an important part of his Judean identity) in order to interact with gentiles (and he rebukes his colleagues for refusing to do so [Gal 2:11–14]). Yet other aspects of his identity are more important and also less flexible: his "in-Christness" (which he shares with gentiles) and his birth as a Judean (which he does not share with gentiles). In closing, I consider the implications this reading has for the identities of the members of his audience, who are simultaneously gentiles, in Christ, and adopted sons of God.
The proteasome inhibitor MG-132 sensitizes PC-3 prostate cancer cells to ionizing radiation by a DNA-PK-independent mechanism
Authors: Pajonk Frank , van Ophoven Arndt , Weissenberger Christian , McBride William H
Published: July 2005

Background

By modulating the expression levels of specific signal transduction molecules, the 26S proteasome plays a central role in determining cell cycle progression or arrest and cell survival or death in response to stress stimuli, including ionizing radiation. Inhibition of proteasome function by specific drugs results in cell cycle arrest, apoptosis and radiosensitization of many cancer cell lines. This study investigates whether there is also a concomitant increase in cellular radiosensitivity if proteasome inhibition occurs only transiently before radiation. Further, since proteasome inhibition has been shown to activate caspase-3, which is involved in apoptosis, and caspase-3 can cleave DNA-PKcs, which is involved in DNA-double strand repair, the hypothesis was tested that caspase-3 activation was essential for both apoptosis and radiosensitization following proteasome inhibition.

Methods

Prostate carcinoma PC-3 cells were treated with the reversible proteasome inhibitor MG-132. Cell cycle distribution, apoptosis, caspase-3 activity, DNA-PKcs protein levels and DNA-PK activity were monitored. Radiosensitivity was assessed using a clonogenic assay.

Results

Inhibition of proteasome function caused cell cycle arrest and apoptosis but this did not involve early activation of caspase-3. Short-time inhibition of proteasome function also caused radiosensitization but this did not involve a decrease in DNA-PKcs protein levels or DNA-PK activity.

Conclusion

We conclude that caspase-dependent cleavage of DNA-PKcs during apoptosis does not contribute to the radiosensitizing effects of MG-132.
The necessary future of chiropractic education: a North American perspective
Authors: Wyatt Lawrence H , Perle Stephen M , Murphy Donald R , Hyde Thomas E
Published: July 2005

The chiropractic educational system in North America is currently in a state of flux. The attempted conversion of some chiropractic schools into "universities" and the want of university affiliation for chiropractic schools suggests that we are searching for a better alternative to the present system. In the early 20th century, the Flexner Report helped transform modern medical education into a discipline that relies on scientific and clinical knowledge. Some have wondered if it is time for a Flexner-type report regarding the education of doctors of chiropractic. This article outlines the current challenges within the chiropractic educational system and proposes positive changes for that system.
Human peripheral blood monocytes express protease receptor-2 and respond to receptor activation by production of IL-6, IL-8, and IL-1β
Authors: Johansson Ulrika , Lawson Charlotte , Dabare Michael , Syndercombe-Court Denise , Newland Adrian C , Howells Gareth L , Macey Marion G
Published: July 2005

Protease-activated receptor-2 (PAR-2) belongs to a family of G-coupled receptors activated by proteolytic cleavage to reveal a tethered ligand. PAR-2 is activated by trypsin and trypsin-like serine proteases and experimentally, by receptor-activating peptides (APs), which mimic the tethered ligand. PAR-2 has recently been implicated in proinflammatory immune responses. For example, PAR-2−/− mice exhibit markedly diminished contact hypersensitivity reactions and are completely resistant to adjuvant-induced arthritis. The present study shows that human blood monocytes express low-level cell-surface PAR-2 ex vivo, which is up-regulated upon cell purification by the mobilization of intracellular stores of PAR-2 protein. PAR-2 expression is also present on monocyte-derived macrophages, but only a small proportion of monocyte-derived dendritic cells (DC) is PAR-2+, and blood DC are PAR–. Freshly isolated monocytes responded to the PAR-2 AP ASKH 95 (2-furoyl-LIGKV-OH) with the generation of a calcium flux and production of interleukin (IL)-1β, IL-6, and IL-8. The results presented thus suggest that PAR-2 contributes to inflammatory responses by inducing the production of proinflammatory cytokines in peripheral blood monocytes.
Adjuvant Treatment for Resectable Pancreatic Cancer
Authors: Chua Yu Jo , Cunningham David
Published: July 2005

There are relatively few randomized studies of adjuvant chemoradiotherapy and chemotherapy in patients with resected pancreatic adenocarcinoma. The European Study Group for Pancreatic Cancer 1 (ESPAC1) trial is the largest study of adjuvant treatment to date. The results of ESPAC1 are discussed in the context of other evidence from previous randomized studies, which have also been combined in a meta-analysis. Overall, the existing data show a clear benefit for postoperative adjuvant chemotherapy, which has not been demonstrated for adjuvant chemoradiotherapy. The subgroup of patients with resection margin positive disease did seem to benefit less from adjuvant chemotherapy, and showed a trend towards improved survival with chemoradiotherapy. Adjuvant chemoradiotherapy should be evaluated further in this latter group of patients. The optimal chemotherapy regimen for use as adjuvant treatment is the subject of ongoing trials. Other strategies which should be explored include neoadjuvant treatment and the incorporation of novel targeted agents into management.
Molecular Markers of Early Pancreatic Cancer
Authors: Goggins Michael
Published: July 2005

Pancreatic cancer is a deadly disease and the fourth most common cause of cancer death in the United States. Since chemotherapy and radiotherapy have thus far largely failed to significantly improve the survival of patients with pancreatic ductal adenocarcinoma, there is considerable interest in identifying better diagnostic markers of pancreatic neoplasia. Not only could better markers improve the early diagnosis of pancreatic cancer and allow more patients to undergo curative surgical resection, but also could potentially be used for patients at high risk of developing pancreatic cancer to identify precancerous lesions while they are amenable to cure. A wealth of information has recently become available about gene expression, DNA methylation, and proteomics alterations that occur in pancreatic cancers creating hope that better diagnostic markers of pancreatic cancer will be soon forthcoming.
Role of Genomic Markers in Colorectal Cancer Treatment
Authors: Allen Wendy L. , Johnston Patrick G.
Published: July 2005

For the last four decades, fluorouracil (FU) has been the main treatment of choice in colorectal cancer (CRC) in both the advanced and adjuvant settings. In the advanced setting, FU monotherapy produces response rates of only 10% to 20%. Furthermore, in resected stage III CRC, FU monotherapy has increased overall survival by only 20%. The combination of FU with newer therapies such as oxaliplatin and irinotecan has significantly improved response rates to 40% to 50%. Despite these improvements, more than half of advanced CRC patients derive no benefit from treatment; this is due to either acquired or inherent drug resistance. This review aims to highlight the current prognostic and predictive markers that have been identified for CRC to date. The limited use of these predictive markers underscores the importance of and need for multiple marker testing in order to improve response rates and decrease toxicity. This review will also focus on high throughput methods to identify panels of predictive markers for CRC, which ultimately aim to tailor treatment according to an individual patient and tumor profile.
Autosomal Dominant Neurohypophyseal Diabetes Insipidus with Linkage to Chromosome 20p13 but without Mutations in the AVP-NPII Gene
Authors: Ye Lei , Li Xiaoying , Chen Ying , Sun Hongtao , Wang Weiqing , Su Tingwei , Jiang Lei , Cui Bin , Ning Guang
Published: July 2005

Context: Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) has been known as a rare disorder transmitted as an autosomal dominant trait, characterized by polyuria and polydipsia, and caused by deficient neurosecretion of arginine vasopressin precursor (AVP-NPII). We reported an ADNDI family with linkage to chromosome 20p13 but without mutations in the AVP-NPII gene.

Objective: The objective of this study was to identify the corresponding locus responsible for ADNDI in a family without AVP-NP II gene mutations.

Subjects and Methods: Two families with ADNDI were diagnosed by water deprivation test. The AVP-NPII gene was amplified by PCR and sequenced. A genomewide scan was performed in one family using 400 microsatellite markers covering 22 autosomes.

Results: A 3-bp deletion (1827–1829delAGG) of AVP-NPII gene was identified in the affected individuals in one family. Although no mutations could be detected in the coding, the promoter, and intronic regions of AVP-NPII gene in the other family, a maximum LOD score of 1.202999 (θ = 0.00) was obtained at marker D20S889 by genomewide scan, and a 7-cM interval on chromosome 20p13 was defined by fine mapping with markers D20S199–D20S849. Furthermore, the intragenic region that regulates AVP-NPII and oxytocin expression as an enhancer element and the UBCE7IP5 gene that participates in prohormone degradation were sequenced. No alterations could be detected either.

Conclusion: The corresponding locus responsible for ADNDI is possibly heterogeneous regarding the slightly different clinical features in these two families.
Effects of Calcium Supplementation on Body Weight and Blood Pressure in Normal Older Women: A Randomized Controlled Trial
Authors: Reid Ian R. , Horne Anne , Mason Barbara , Ames Ruth , Bava Usha , Gamble Gregory D.
Published: July 2005

Context: Epidemiological data suggest that high calcium intakes are associated with decreased body weight and blood pressure. However, there is little evidence from randomized trials that addresses these important issues.

Objective: The objective of this study was to assess the long-term effects of calcium on body weight and blood pressure.

Design: This is a substudy of an ongoing, double-blind, randomized, controlled trial of calcium supplementation. End points were assessed at 30 months.

Setting: This study was performed at a university medical center.

Participants: Normal postmenopausal women (mean age, 74 yr; mean weight, 67 kg; mean blood pressure, 134/70 mm Hg at baseline) participated in this study.

Intervention: Study subjects were treated with calcium (1 g/d; n = 732) and placebo (n = 739).

Main Outcome Measures: Body weight and blood pressure were the main outcome measures.

Results: Weight decreased by 368 ± 132 g (mean ± se) with calcium treatment and by 369 ± 134 g with placebo (P = 0.93). Fat and lean masses did not show an effect of calcium. Blood pressure showed transient reductions of 1–2 mm Hg at 6 months in the calcium group, resulting in a significant between-group difference only for systolic pressure (P = 0.048). At 30 months, the change from baseline in systolic pressure was 0.0 ± 0.9 mm Hg in the calcium group and 2.4 ± 0.9 mm Hg in the placebo group (P = 0.14). For diastolic pressures, the changes were −0.2 ± 0.4 and 0.8 ± 0.4 mm Hg, respectively (P = 0.13). In those with baseline calcium intakes less than 600 mg/d, the treatment effect was greater and did persist.

Conclusions: Calcium supplementation of 1 g/d does not produce biologically significant effects on body weight, and its hypotensive effect is small and transient in most women.
Acute Hyperglycemia Does Not Affect the Reactivity of Coronary Microcirculation in Humans
Authors: Capaldo Brunella , Galderisi Maurizio , Turco Anna Amelia , D’Errico Arcangelo , Turco Salvatore , Rivellese Angela Albarosa , de Simone Giovanni , de Divitiis Oreste , Riccardi Gabriele
Published: July 2005

Objective: There is some evidence that acute hyperglycemia (H) may cause vascular dysfunction in normal subjects. This study investigates whether acute, short-term H affects coronary vasodilatory function in healthy subjects.

Design: Diastolic peak flow velocity in the left anterior descending coronary artery was measured at rest and after dipyridamole (0.56 mg/kg over 4 min) using transthoracic color Doppler echocardiography in 13 healthy men. Coronary flow reserve (CFR) was defined as the ratio of dipyridamole-induced coronary peak diastolic to resting peak diastolic flow velocity. CFR was measured both in euglycemia (E) and after 3 h H (∼14 mmol/liter) by a variable infusion of glucose and octreotide (0.4 mg/h) to prevent increase in insulin concentration.

Results: Fasting plasma glucose increased to 14.3 ± 0.33 mmol/liter during the study and maintained variability within less than 10%. Plasma insulin remained nearly stable during H. Resting diastolic flow velocity was 18.5 ± 0.6 cm/sec in E and increased to 20.0 ± 0.7 cm/sec during H (P < 0.005). Dipyridamole infusion produced a marked increase in coronary flow velocity, which reached values of 50.8 ± 2.9 cm/sec in E and 51.8 ± 2.1 cm/sec in H (P = not significant). CFR was 2.78 ± 0.16 in E and 2.59 ± 0.12 in H (P = not significant).

Conclusion: Our study indicates that short-term hyperglycemia does not affect the vasodilatory response of coronary microcirculation in healthy subjects.
Molecular Evidence of Placental Hypoxia in Preeclampsia
Authors: Soleymanlou Nima , Jurisica Igor , Nevo Ori , Ietta Francesca , Zhang Xin , Zamudio Stacy , Post Martin , Caniggia Isabella
Published: July 2005

Background: Oxygen plays a central role in human placental pathologies including preeclampsia, a leading cause of fetal and maternal death and morbidity. Insufficient uteroplacental oxygenation in preeclampsia is believed to be responsible for the molecular events leading to the clinical manifestations of this disease.

Design: Using high-throughput functional genomics, we determined the global gene expression profiles of placentae from high altitude pregnancies, a natural in vivo model of chronic hypoxia, as well as that of first-trimester explants under 3 and 20% oxygen, an in vitro organ culture model. We next compared the genomic profile from these two models with that obtained from pregnancies complicated by preeclampsia. Microarray data were analyzed using the binary tree-structured vector quantization algorithm, which generates global gene expression maps.

Results: Our results highlight a striking global gene expression similarity between 3% O2-treated explants, high-altitude placentae, and importantly placentae from preeclamptic pregnancies. We demonstrate herein the utility of explant culture and high-altitude placenta as biologically relevant and powerful models for studying the oxygen-mediated events in preeclampsia.

Conclusion: Our results provide molecular evidence that aberrant global placental gene expression changes in preeclampsia may be due to reduced oxygenation and that these events can successfully be mimicked by in vivo and in vitro models of placental hypoxia.
Severe Growth Hormone Insensitivity Resulting from Total Absence of Signal Transducer and Activator of Transcription 5b
Authors: Hwa Vivian , Little Brian , Adiyaman Pelin , Kofoed Eric M. , Pratt Katherine L. , Ocal Gonul , Berberoglu Merih , Rosenfeld Ron G.
Published: July 2005

Context: The central clinical feature of GH insensitivity (GHI) is severe growth failure associated with elevated serum concentrations of GH and abnormally low serum levels of IGF-I. GHI can be the result of an abnormality in the GH receptor or aberrancies downstream of the GH receptor.

Objective: We investigated the GH-IGF-I axis in a young female GHI subject who presented with a height of 114 cm (−7.8 sd score) at age 16.4 yr.

Patient: The subject, from a consanguineous pedigree, had circulating levels of GH and GH-binding protein that were normal to elevated, whereas IGF-I (7.2 ng/ml; normal, 242–600), IGF-binding protein-3 (543 ng/ml; normal, 2500–4800), and acid-labile subunit (1.22 μg/ml; normal, 5.6–16) levels were abnormally low and failed to increase during an IGF-I generation test.

Design: Dermal fibroblast cultures were established with the consent of the patient and family. Immunoblot analysis of cell lysates and DNA sequencing of her signal transducer and activator of transcription 5b (STAT5b), a critical intermediate of the GH-IGF-I axis, were performed.

Results: Sequencing of the STAT5b gene revealed a novel homozygous insertion of a single nucleotide in exon 10. The insertion resulted in a frame shift, leading to early protein termination and consequent lack of immunodetectable STAT5b protein.

Conclusion: The identification of a second case of severe growth failure associated with STAT5b mutation implicates a unique and critical role for STAT5b in GH stimulation of IGF-I gene expression and statural growth.
Dose-dependent control of proliferation and sperm specification by FOG-1/CPEB
Authors: Thompson Beth E. , Bernstein David S. , Bachorik Jennifer L. , Petcherski Andrei G. , Wickens Marvin , Kimble Judith
Published: July 2005

RNA-binding proteins control germline development in metazoans. This work focuses on control of the C. elegans germline by two RNA-binding proteins: FOG-1, a CPEB homolog; and FBF, a PUF family member. Previous studies have shown that FOG-1 specifies the sperm fate and that FBF promotes proliferation. Here, we report that FOG-1 also promotes proliferation. Whereas fbf-1 fbf-2 double mutants make ∼120 germ cells, fog-1; fbf-1 fbf-2 triple mutants make only ∼10 germ cells. The triple mutant germline divides normally until early L2, when germ cells prematurely enter meiosis and begin oogenesis. Importantly, fog-1/+; fbf-1 fbf-2 animals make more germ cells than fbf-1 fbf-2 double mutants, demonstrating that one dose of wild-type fog-1promotes proliferation more effectively than two doses – at least in the absence of FBF. FOG-1 protein is barely detectable in proliferating germ cells, but abundant in germ cells destined for spermatogenesis. Based on fog-1 dose effects, together with the gradient of FOG-1 protein abundance, we suggest that low FOG-1 promotes proliferation and high FOG-1 specifies spermatogenesis. FBF binds specifically to regulatory elements in the fog-1 3′UTR, and FOG-1 increases in animals lacking FBF. Therefore, FBF represses fog-1 expression. We suggest that FBF promotes continued proliferation, at least in part, by maintaining FOG-1 at a low level appropriate for proliferation. The dose-dependent control of proliferation and cell fate by FOG-1 has striking parallels with Xenopus CPEB, suggesting a conserved mechanism in animal development.
Tec29controls actin remodeling and endoreplication during invagination of theDrosophilaembryonic salivary glands
Authors: Chandrasekaran Vidya , Beckendorf Steven K.
Published: July 2005

Epithelial invagination is necessary for formation of many tubular organs,one of which is the Drosophila embryonic salivary gland. We show that actin reorganization and control of endocycle entry are crucial for normal invagination of the salivary placodes. Embryos mutant for Tec29, the Drosophila Tec family tyrosine kinase, showed delayed invagination of the salivary placodes. This invagination delay was partly the result of an accumulation of G-actin in the salivary placodes, indicating that Tec29 is necessary for maintaining the equilibrium between G- and F-actin during invagination of the salivary placodes. Furthermore, normal invagination of the salivary placodes appears to require the proper timing of the endocycle in these cells; Tec29 must delay DNA endoreplication in the salivary placode cells until they have invaginated into the embryo. Taken together, these results show that Tec29 regulates both the actin cytoskeleton and the cell cycle to facilitate the morphogenesis of the embryonic salivary glands. We suggest that apical constriction of the actin cytoskeleton may provide a temporal cue ensuring that endoreplication does not begin until the cells have finished invagination.
Quantification of stem cell factor mRNA levels in the rat testis: usefulness of clusterin mRNA as a marker of the amount of mRNA of sertoli cell origin in post pubertal rats
Authors: Plotton Ingrid , Sanchez Pascale , Perrard Marie Hélène , Durand Phillipe , Lejeune Hervé
Published: July 2005

Spermatogenesis is a complex cellular process regulated by gonadotrophins and local cell–cell interactions. Stem cell factor (SCF) is one of the paracrine factors, produced by the Sertoli cells, involved in the local regulation of spermatogenesis. Measurement of its testicular level is important for addressing its role in testis physiopathology. However, the relative cell composition of experimental and pathological testis samples may lead to misinterpretation in relating SCF mRNA levels to the amount of RNA extracted from the whole tissue sample. Taking into account the relative RNA content of Sertoli cell origin should provide more significant data. In the present study, three sets of experiments were intended for modifying the proportion of RNA of Sertoli cell origin in RNA extracted from whole testis tissue samples: during postnatal development; following methoxy-acetic acid (MAA) administration; and after injecting a long-acting gonadotrophin-releasing hormone agonist (GnRHa). In a first step, we demonstrated clusterin mRNA level stability in purified Sertoli cell preparations between 20 days and adulthood, and following MAA or GnRHa treatment. In a second step, we used a competitive RT-PCR assay to measure SCF and clusterin mRNA levels and expressed the amount of SCF mRNA relative to the amount of clusterin mRNA under the above experimental conditions. The SCF/clusterin mRNA level ratio was found to remain roughly stable from 20 days post-partum to adulthood; i.e. during the development of spermatogenesis. MAA administration led to an overall increase in the SCF/clusterin mRNA level ratio between 7 and 14 days after administration, consistent with the replenishment of the testis with pachytene spermatocytes and round spermatids. Conversely, after long-acting GnRHa injection, the SCF/clusterin mRNA level ratio decreased only slightly from day 21 onward. Hence, the present studies indicate that, under physiopathological conditions, the amount of clusterin mRNA is a good marker of the amount of RNA of Sertoli cell origin in testis samples at day 20 or later; different experimental alterations of spermatogenesis are associated with different patterns of SCF mRNA levels; the relationship between FSH and SCF in vivo is not as simple as that described in vitro.
The estrogen receptor α Σ3 mRNA splicing variant is differentially regulated by estrogen and progesterone in the rat uterus
Authors: Varayoud J , Ramos J G , Monje L , Bosquiazzo V , Muñoz-de-Toro M , Luque E H
Published: July 2005

The gene for estrogen receptor α (ERα) has been shown to be under complex hormonal control and its activity can be regulated by mRNA alternative splicing. Here we examined the regulation of ERα transcription and translation in the rat uterus by ovarian steroid hormones. We examined whether expression of ERα mRNA splice isoforms is hormonally regulated in ovariectomized (OVX) and cycling rats. Adult OVX female rats were treated daily with 17-β estradiol (E2) (0.05 μg/rat or 5 μg/rat), progesterone (P4) (1 mg/rat) or a combination of both hormones for 4 days. Animals were killed 24 h after the last injection and uterine horns were removed. In order to determine whether ERα mRNA isoforms are differentially expressed under various physiological conditions, animals were evaluated at proestrus, estrus and diestrus. The ERα protein and mRNA were detected by immunohistochemistry and comparative RT-PCR analysis respectively. The presence of ERα mRNA isoforms was evaluated using a nested RT-PCR assay. In OVX control rats, ERα mRNA and protein levels were high, demonstrating a constitutive expression of the ERα gene in the uterus. When animals received P4 or the high dose of E2, a significant decrease in both ERα mRNA and protein was observed in the uterus. However, when rats were protein was treated with the low dose of E2, only the ERα down-regulated; no changes were observed in ERα mRNA expression. In addition to the full-length ERα mRNA, OVX control rat uteri expressed three shorter transcripts: Σ3, Σ4 and Σ3,4 (lacking exon 3, exon 4, or both 3 and 4 respectively). Surprisingly, when OVX animals were treated with P4, the low dose of E2 or a combination of both steroids, expression of the Σ3 isoform was completely abolished. During the estrous cycle, all ERα mRNA splicing variants were detected at proestrus and estrus. However, in diestrus, significant low levels of the Σ3 isoform were observed. In summary, our results suggest a dose-dependent relationship between E2 concentrations and the level of control in the ERα transcription–translation cascade. Moreover, the alternative splicing of the ERα primary transcript is influenced by the hormonal milieu, suggesting that these events could affect the estrogen responsiveness of the rat uterus during the estrous cycle.
Amniotic IGF-I supplementation of growth-restricted fetal sheep alters IGF-I and IGF receptor type 1 mRNA and protein levels in placental and fetal tissues
Authors: Shaikh S , Bloomfield F H , Bauer M K , Phua H H , Gilmour R S , Harding J E
Published: July 2005

We have previously reported that chronic intra-amniotic supplementation of the late gestation growth-restricted (IUGR) ovine fetus with IGF-I (20 μg/day) increased gut growth but reduced liver weight and circulating IGF-I concentrations. Here we report mRNA and protein levels of IGF-I, the type 1 IGF receptor (IGF-1R) and IGF-binding proteins (IGFBP)-1, -2 and -3 in fetal gut, liver, muscle and placenta from fetuses in that earlier study in an attempt to explain these contrasting results. mRNA and protein were extracted from tissues obtained at post mortem at 131 days of gestation (term, 145 days) from three groups of fetuses (control, IUGR+saline and IUGR+IGF-I, n=9 per group). Control fetuses were unembolised and untreated. In the IUGR groups, growth restriction was induced from 113 to 120 days by placental embolisation; from 120 to 130 days fetuses were treated with daily intra-amniotic injections of either saline or 20 μg IGF-I. mRNA was measured by RT-PCR or real-time RT-PCR, and protein by Western blot. In liver, muscle and placenta, IGF-I mRNA and protein levels were reduced by between 8 and 30% in IGF-I-treated fetuses compared with saline-treated fetuses and controls with no change in IGF-1R mRNA or protein levels. In contrast, in the gut, IGF-I mRNA and protein levels were not significantly altered with IGF-I treatment, but IGF-1R levels were increased, especially in the jejunum. Immunolocalisation demonstrated that IGF-1R expression was confined to the luminal aspect of the gut. mRNA levels of all three IGFBPs were reduced in the gut of IGF-I-treated fetuses, but hepatic expression was significantly increased. These data demonstrated tissue-specific regulation of IGF-I, IGF-1R and IGFBPs-1, -2 and -3 in response to intra-amniotic IGF-I supplementation, though the underlying mechanisms remain obscure.