bluuebunny/crossref_metadata_2025 huggingface dataset:
The management of imaging dose during image‐guided radiotherapy: Report of the AAPM Task Group 75
Authors: Murphy Martin J. , Balter James , Balter Stephen , BenComo Jose A. , Das Indra J. , Jiang Steve B. , Ma C.‐M. , Olivera Gustavo H. , Rodebaugh Raymond F. , Ruchala Kenneth J. , Shirato Hiroki , Yin Fang‐Fang
Published: October 2007

Radiographic image guidance has emerged as the new paradigm for patient positioning, target localization, and external beam alignment in radiotherapy. Although widely varied in modality and method, all radiographic guidance techniques have one thing in common—they can give a significant radiation dose to the patient. As with all medical uses of ionizing radiation, the general view is that this exposure should be carefully managed. The philosophy for dose management adopted by the diagnostic imaging community is summarized by the acronym ALARA, i.e., as low as reasonably achievable. But unlike the general situation with diagnostic imaging and image‐guided surgery, image‐guided radiotherapy (IGRT) adds the imaging dose to an already high level of therapeutic radiation. There is furthermore an interplay between increased imaging and improved therapeutic dose conformity that suggests the possibility of optimizing rather than simply minimizing the imaging dose. For this reason, the management of imaging dose during radiotherapy is a different problem than its management during routine diagnostic or image‐guided surgical procedures. The imaging dose received as part of a radiotherapy treatment has long been regarded as negligible and thus has been quantified in a fairly loose manner. On the other hand, radiation oncologists examine the therapy dose distribution in minute detail. The introduction of more intensive imaging procedures for IGRT now obligates the clinician to evaluate therapeutic and imaging doses in a more balanced manner. This task group is charged with addressing the issue of radiation dose delivered via image guidance techniques during radiotherapy. The group has developed this charge into three objectives: (1) Compile an overview of image‐guidance techniques and their associated radiation dose levels, to provide the clinician using a particular set of image guidance techniques with enough data to estimate the total diagnostic dose for a specific treatment scenario, (2) identify ways to reduce the total imaging dose without sacrificing essential imaging information, and (3) recommend optimization strategies to trade off imaging dose with improvements in therapeutic dose delivery. The end goal is to enable the design of image guidance regimens that are as effective and efficient as possible.
Importance of point‐by‐point back projection correction for isocentric motion in digital breast tomosynthesis: Relevance to morphology of structures such as microcalcifications
Authors: Chen Ying , Lo Joseph Y. , Dobbins James T.
Published: October 2007

Digital breast tomosynthesis is a three‐dimensional imaging technique that provides an arbitrary set of reconstruction planes in the breast from a limited‐angle series of projection images acquired while the x‐ray tube moves. Traditional shift‐and‐add (SAA) tomosynthesis reconstruction is a common mathematical method to line up each projection image based on its shifting amount to generate reconstruction slices. With parallel‐path geometry of tube motion, the path of the tube lies in a plane parallel to the plane of the detector. The traditional SAA algorithm gives shift amounts for each projection image calculated only along the direction of x‐ray tube movement. However, with the partial isocentric motion of the x‐ray tube in breast tomosynthesis, small objects such as microcalcifications appear blurred (for instance, about 1–4 pixels in blur for a microcalcification in a human breast) in traditional SAA images in the direction perpendicular to the direction of tube motion. Some digital breast tomosynthesis algorithms reported in the literature utilize a traditional one‐dimensional SAA method that is not wholly suitable for isocentric motion. In this paper, a point‐by‐point back projection (BP) method is described and compared with traditional SAA for the important clinical task of evaluating morphology of small objects such as microcalcifications. Impulse responses at different three‐dimensional locations with five different combinations of imaging acquisition parameters were investigated. Reconstruction images of microcalcifications in a human subject were also evaluated. Results showed that with traditional SAA and view angle of tube movement with respect to the detector, at the same height above the detector, the in‐plane blur artifacts were obvious for objects farther away from x‐ray source. In a human subject, the appearance of calcifications was blurred in the direction orthogonal to the tube motion with traditional SAA. With point‐by‐point BP, the appearance of calcifications was sharper. The point‐by‐point BP method demonstrated improved rendition of microcalcifications in the direction perpendicular to the tube motion direction. With wide angles or for imaging of larger breasts, this point‐by‐point BP rather than the traditional SAA should also be considered as the basis of further deblurring algorithms that work in conjunction with the BP method.
Investigation of the support vector machine algorithm to predict lung radiation‐induced pneumonitis
Authors: Chen Shifeng , Zhou Sumin , Yin Fang‐Fang , Marks Lawrence B. , Das Shiva K.
Published: October 2007

The purpose of this study is to build and test a support vector machine (SVM) model to predict for the occurrence of lung radiation‐induced Grade 2+ pneumonitis. SVM is a sophisticated statistical technique capable of separating the two categories of patients (with/without pneumonitis) using a boundary defined by a complex hypersurface. Despite the complexity, the SVM boundary is only minimally influenced by outliers that are difficult to separate. By contrast, the simple hyperplane boundary computed by the more commonly used and related linear discriminant analysis method is heavily influenced by outliers. Two SVM models were built using data from 219 patients with lung cancer treated using radiotherapy (34 diagnosed with pneumonitis). One model selected input features from all dose and non‐dose factors. For comparison, the other model selected input features only from lung dose‐volume factors. Model predictive ability was evaluated using ten‐fold cross‐validation and receiver operating characteristics (ROC) analysis. For the model , the area under the cross‐validated ROC curve was 0.76 . Compared to the corresponding area of 0.71 , the predictive ability of was improved, indicating that non‐dose features are important contributors to separating patients with and without pneumonitis. Among the input features selected by model , the two with highest importance for predicting lung pneumonitis were: (a) generalized equivalent uniform doses close to the mean lung dose, and (b) chemotherapy prior to radiotherapy. The model is publicly available via internet access.
Examination of geometric and dosimetric accuracies of gated step‐and‐shoot intensity modulated radiation therapy
Authors: Wiersma R. D. , Xing L.
Published: October 2007

Due to the complicated technical nature of gated radiation therapy, electronic and mechanical limitations may affect the precision of delivery. The purpose of this study is to investigate the geometric and dosimetric accuracies of gated step‐and‐shoot intensity modulated radiation treatments (SS‐IMRT). Unique segmental MLC plans are designed, which allow quantitative testing of the gating process. Both ungated and gated deliveries are investigated for different dose sizes, dose rates, and gating window times using a commercial treatment system (Varian Trilogy) together with a respiratory gating system [Varian Real‐Time Position Management system]. Radiographic film measurements are used to study the geometric accuracy, where it is found that with both ungated and gated SS‐IMRT deliveries the MLC leaf divergence away from planned is less than or equal to the MLC specified leaf tolerance value for all leafs (leaf tolerance being settable from ). Nevertheless, due to the MLC controller design, failure to define a specific leaf tolerance value suitable to the SS‐IMRT plan can lead to undesired geometric effects, such as leaf motion of up to the maximum leaf tolerance value occurring after the beam is turned on. In this case, gating may be advantageous over the ungated case, as it allows more time for the MLC to reach the intended leaf configuration. The dosimetric precision of gated SS‐IMRT is investigated using ionization chamber methods. Compared with the ungated case, it is found that gating generally leads to increased dosimetric errors due to the interruption of the “overshoot phenomena.” With gating the average timing deviation for intermediate segments is found to be , compared to for the ungated case. For a plan delivered at this would correspond to an average segment dose error of and for gated and ungated deliveries, respectively. The maximum dosimetric errors for individual intermediate segments are found to deviate by up to from their planned value when delivered at using gating, this compares to only for the ungated case.
Nanomechanical Basis of Selective Gating by the Nuclear Pore Complex
Authors: Lim Roderick Y. H. , Fahrenkrog Birthe , Köser Joachim , Schwarz-Herion Kyrill , Deng Jie , Aebi Ueli
Published: October 2007

The nuclear pore complex regulates cargo transport between the cytoplasm and the nucleus. We set out to correlate the governing biochemical interactions to the nanoscopic responses of the phenylalanineglycine (FG)–rich nucleoporin domains, which are involved in attenuating or promoting cargo translocation. We found that binding interactions with the transport receptor karyopherin-β1 caused the FG domains of the human nucleoporin Nup153 to collapse into compact molecular conformations. This effect was reversed by the action of Ran guanosine triphosphate, which returned the FG domains into a polymer brush-like, entropic barrier conformation. Similar effects were observed in
Xenopus
oocyte nuclei in situ. Thus, the reversible collapse of the FG domains may play an important role in regulating nucleocytoplasmic transport.
Video Cameras on Wild Birds
Authors: Rutz Christian , Bluff Lucas A. , Weir Alex A. S. , Kacelnik Alex
Published: October 2007

New Caledonian crows (Corvus moneduloides) are renowned for using tools for extractive foraging, but the ecological context of this unusual behavior is largely unknown. We developed miniaturized, animal-borne video cameras to record the undisturbed behavior and foraging ecology of wild, free-ranging crows. Our video recordings enabled an estimate of the species' natural foraging efficiency and revealed that tool use, and choice of tool materials, are more diverse than previously thought. Video tracking has potential for studying the behavior and ecology of many other bird species that are shy or live in inaccessible habitats.
Ordered Phosphorylation Governs Oscillation of a Three-Protein Circadian Clock
Authors: Rust Michael J. , Markson Joseph S. , Lane William S. , Fisher Daniel S. , O'Shea Erin K.
Published: October 2007

The simple circadian oscillator found in cyanobacteria can be reconstituted in vitro using three proteins—KaiA, KaiB, and KaiC. The total phosphorylation level of KaiC oscillates with a circadian period, but the mechanism underlying its sustained oscillation remains unclear. We have shown that four forms of KaiC differing in their phosphorylation state appear in an ordered pattern arising from the intrinsic autokinase and autophosphatase rates of KaiC and their modulation by KaiA. Kinetic and biochemical data indicate that one of these phosphoforms inhibits the activity of KaiA through interaction with KaiB, providing the crucial feedback that sustains oscillation. A mathematical model constrained by experimental data quantitatively reproduces the circadian period and the distinctive dynamics of the four phosphoforms.
FIRE DAMAGE ON CARBON FIBER MATERIALS CHARACTERIZED BY THZ WAVES
Authors: KARPOWICZ NICHOLAS , DAWES DAVID , PERRY MARK J. , ZHANG X. -C.
Published: October 2007

We apply THz imaging technology to evaluate fire damage to a variety of carbon fiber composite samples. The majority of carbon fiber materials have polarization-dependent reflectivities in the THz frequency range, and we show how the polarization dependence changes versus the burn damage level. Additionally, time domain information acquired through a THz time-domain spectroscopy (TDS) system provides further information with which to characterize the damage. The technology is discussed in terms of non-destructive testing applications to the defense and aerospace industries.
REMOTE IDENTIFICATION OF FOREIGN SUBJECTS
Authors: SOKOLNIKOV ANDRE
Published: October 2007

There are occasions when identification of individuals in civil clothes or uniform may be necessary. In such a case, the ability of terahertz radiation to react to different configuration of, for example, plastic objects, such as tablets, etc. may be used to give a warning sign if the approaching subject is foreign, be he or she in uniform (the one that looks like your own) or in civil clothes. The identification gives an advantage of “checking the credentials” without asking for them. This feature may be especially useful when a military detachment is located close to the adversary occupied territory. The idea for such an identification device came from real situations similar to those that have taken place in Iraq, etc. The code for identification is built in the password tablet. The tablet coatings are semi-transparent to the THz radiation and do not scatter it significantly. The THz pulses, incident on the tablet surface, penetrate through the different coating layers. At each interface a portion of the pulse is reflected back to the detector. The amplitude of the reflected radiation is recorded as a function of time. The resulting pattern is compared with the password.
THE (2+2)-SIGNATURE AND THE (1+1)-MATRIX-BRANE
Authors: NIETO J. A.
Published: October 2007

We discuss different aspects of the (2+2)-signature from the point of view of the quatl theory. In particular, we compare two alternative approaches to such a spacetime signature, namely the (1+1)-matrix-brane and the (2+2)-target spacetime of a string. This analysis also reveals hidden discrete symmetries of the (2+2)-brane action associated with the (2+2)-dimensional sector of a (2+10)-dimensional target background.
THE ACCRETION GEOMETRY IN RADIO-LOUD ACTIVE GALAXIES
Authors: BALLANTYNE D. R.
Published: October 2007

We review the latest attempts to determine the accretion geometry in radio-loud active galactic nuclei (AGN). These objects, which comprise ~ 10–20% of the AGN population, produce powerful collimated radio jets that can extend thousands of parsecs from the center of the host galaxy. Recent multiwavelength surveys have shown that radio-loudness is more common in low-luminosity AGN than in higher luminosity Seyfert galaxies or quasars. These low-luminosity AGN have small enough accretion rates that they are most likely accreting via a geometrically thick and radiatively inefficient accretion flow. In contrast, X-ray spectroscopic observations of three higher luminosity broad-line radio galaxies (3C 120, 4C+74.26 and PG 1425+267) have found evidence for an untruncated thin disk extending very close to the black hole. These tentative detections indicate that, for this class of radio-loud AGN, the accretion geometry is very similar to their radio-quiet counterparts. These observations suggest that there are three conditions to jet formation that must be satisfied: the presence of a rapidly spinning black hole, an accretion flow with a large H/r ratio, and a favorable magnetic field geometry.
REFLECTIVE SCATTERING FROM UNITARITY SATURATION
Authors: TROSHIN S. M. , TYURIN N. E.
Published: October 2007

Proceeding from optical analogy we propose a new physical interpretation of unitarity saturation leading to antishadowing as a reflective scattering. This interpretation of antishadowing is related to the nonperturbative aspects of strong interactions and follows from the specific property of the unitarity saturation when elastic S-matrix S(s, b)|b = 0 → -1 at s→∞. The analogy with Berry phase and experimental consequences of the proposed interpretation as reflective scattering at the LHC and in the cosmic rays studies are discussed.
THE REAL SCALAR FIELD EQUATION FOR NARIAI BLACK HOLE IN THE 5D SCHWARZSCHILD–DE SITTER BLACK STRING SPACE
Authors: LIU MOLIN , LIU HONGYA , WANG CHUNXIAO , PING YONGLI
Published: October 2007

The Nariai black hole, whose two horizons are lying close to each other, is an extreme and important case in the research of black hole. In this paper we study the evolution of a massless scalar field scattered around in 5D Schwarzschild–de Sitter black string space. Using the method shown by Brevik and Simonsen (2001) we solve the scalar field equation as a boundary value problem, where real boundary condition is employed. Then with convenient replacement of the 5D continuous potential by square barrier, the reflection and transmission coefficients (R, T) are obtained. At last, we also compare the coefficients with the usual 4D counterpart.
FEYNMAN DIAGRAMS AND DIFFERENTIAL EQUATIONS
Authors: ARGERI MARIO , MASTROLIA PIERPAOLO
Published: October 2007

We review in a pedagogical way the method of differential equations for the evaluation of D-dimensionally regulated Feynman integrals. After dealing with the general features of the technique, we discuss its application in the context of one- and two-loop corrections to the photon propagator in QED, by computing the Vacuum Polarization tensor exactly in D. Finally, we treat two cases of less trivial differential equations, respectively associated to a two-loop three-point, and a four-loop two-point integral. These two examples are the playgrounds for showing more technical aspects about: Laurent expansion of the differential equations in D (around D = 4); the choice of the boundary conditions; and the link among differential and difference equations for Feynman integrals.
FIBER-OPTIC TEMPERATURE TESTING FOR HIGH VOLTAGE EQUIPMENT
Authors: XIE CHI , LIU NIAN , LIU YING , LIU LU
Published: October 2007

To solve the problem of monitoring the temperature of high-voltage equipment in high-energy physics experiments, a new temperature testing method using fiber optic is presented in this paper, and the photoelectrical probe, the principle of optical fiber and the linear solution of the temperature-sensitive component are introduced. The experiment shows that this method has the advantages of measuring temperature in high-energy physics experiments where there is high voltage, strong magnetic fields, radioactivity and narrow spaces.
OBSERVATION OF HIGH Tc IN THE BILAYERED La2SmxSr1-xMn2O7 PEROVSKITE
Authors: BASITH M. A. , SHAHPARAN M. , HUQ M. , MANJURA HOQUE S. K. , HAKIM M. A.
Published: October 2007

Bulk layered perovskite samples La 2 Sm x Sr 1-x Mn 2 O 7 (x = 0.4, 0.6 and 0.8) were prepared by the conventional solid-state reaction technique and their temperature dependence of electrical resistance and magnetization measurements were performed. The metal-insulator (M-I) transition, magnetic phase transition and the colossal magnetoresisitance phenomena were observed. The M-I transition peak temperature (T p ) shifts towards lower temperature with increasing x while magnetic field shifts T p to the high temperature regime. Experimental results show that layered manganites La 2 Sm x Sr 1-x Mn 2 O 7 (x = 0.4, 0.6 and 0.8) exhibit ferromagnetic-to-paramagnetic transitions at Curie temperature T c ~ 355, 286 and 277 K for x = 0.4, 0.6 and 0.8, respectively. A large deviation between the metal-insulator transition and the magnetic transition temperature is observed for all the doping concentrations. But in the case of well-known ABO 3 type perovskite manganites like La 0.75 Ca 0.25 MnO 3, the M-I transition was found previously very close to magnetic transition. At 78 K, a sharp increase of magnetoresistance was observed at low magnetic fields.
NON-LINEARITIES IN ACCRETION AND WINDS AROUND ROTATING BLACK HOLES USING PSEUDO-KERR GEOMETRY
Authors: MONDAL SOUMEN , CHAKRABARTI SANDIP K.
Published: October 2007

Non-linearities such as shock waves are common in accretion flows around compact objects. Exact quantification of these non-linearities will help testing time-dependent numerical codes. In this paper, we study the detailed properties of these non-linear waves in a steady accretion or wind flows around a rotating black hole. We use a pseudo-Kerr geometry for this purpose. In the context of energy preserving standing shocks, we find that there are two shock locations for a given pair of conserved flow parameters, such as specific energy and angular momentum. We also show that as the Kerr parameter is increased, the shock location moves closer to the black hole. We discuss the astrophysical implications of such solutions.
COMMENT ON THE CHOICE OF TIME IN A TWO-COMPONENT FORMULATION OF THE WHEELER–DEWITT EQUATION
Authors: THIBEAULT MARC , SIMEONE CLAUDIO
Published: October 2007

The two-component formalism in quantum cosmology is revisited with a particular emphasis on the identification of time. Its relation with the appearance of imaginary eigenvalues is established. It is explicitly shown how a good choice of the global time prevents this peculiarity.
INFORMATION LOSS AND TUNNELING RADIATION OF THE NON-STATIONARY DILATON–MAXWELL, BLACK HOLE
Authors: CHEN DEYOU , YANG SHUZHENG
Published: October 2007

Taking the self-gravitational interaction and unfixed background space–time into account, we discuss the tunneling radiation of the Dilaton–Maxwell black hole by the Hamilton–Jacobi method. The result shows that the tunneling rate is related not only to the change of Bekenstein–Hawking entropy, but also to a subtle integral about the black hole mass, which does not satisfy the unitary theory and is different from Parikh and Wilczek's result. This implies that information loss in black hole evaporation is possible.
SCATTERING OF COSMIC STRINGS BY BLACK HOLES: LOOP FORMATION
Authors: DUBATH FLORIAN , SAKELLARIADOU MAIRI , VIALLET CLAUDE MICHEL
Published: October 2007

We study the deformation of a long cosmic string by a nearby rotating black hole. We examine whether the deformation of a cosmic string, induced by the gravitational field of a Kerr black hole, may lead to the formation of a string loop. The segment of the string which enters the ergo-sphere of a rotating black hole gets deformed and, if it is sufficiently twisted, it can self-intersect, chopping off a loop. We find that the formation of a loop, via such a mechanism, is a rare event. It will only arise in a small region of the collision phase space, which depends on the string velocity, the impact parameter and the black hole angular momentum. We conclude that, generically, a long cosmic string is simply scattered, or captured, by a nearby rotating black hole.
ENTROPY BOUND FOR THE TM ELECTROMAGNETIC FIELD IN THE HALF-EINSTEIN UNIVERSE
Authors: BREVIK I. , HERIKSTAD R. , SKRIUDALEN S.
Published: October 2007

An explicit calculation is given of the entropy/energy ratio for the TM modes of the electromagnetic field in the half-Einstein universe. This geometry provides a mathematically convenient and physically instructive example of how the electromagnetic and thermodynamic quantities behave as a function of the non-dimensional parameter δ = 1/2π aT, a being the scale factor and T the temperature. On physical grounds (related to the relaxation time), it is the case of small δ's that is pertinent to thermodynamics. We find that as long as δ is small, the entropy/energy ratio behaves in the same way as for the TE modes. The entropy is thus bounded. The present kind of formalism makes it convenient to study also the influence from frequency dispersion. We discuss an example where a sharp cut-off dispersion relation can in principle truncate the electromagnetic oscillations in the Einstein cavity such that only the lowest mode survives.
ON THE NATURE OF GRAVITATIONAL FORCES
Authors: POPOLO ANTONINO DEL , YEŞILYURT S.
Published: October 2007

In this paper, we will show how the statistics of the gravitational field is changed when the system is characterized by a non-uniform distribution of particles. We will show how the distribution functions W(F) and W(F,dF/dt), giving the joint probability that a test particle is subject to a force F and an associated rate of change of F given by dF/dt, are modified by inhomogeneity. Then we will calculate the first moment of dF/dt to study the effects of inhomogenity on dynamical friction. Finally we will test, by N-Body simulations, that the theoretical W(F) and dF/dt describes correctly the experimental data and we find that the stochastic force distribution obtained for the evolved system is in good agreement with theory. Moreover, we find that in an inhomogeneous background, the friction force is actually enhanced relative to the homogeneous case.
Genetic Determinants of Aggressive Breast Cancer
Authors: Ventura Alejandra C. , Merajver Sofia D.
Published: October 2007

The development and spread of breast and other human cancers are caused by the overexpression, mutation, and/or deletion of specific genes that drive these events. Finding genetic and molecular differences between cancerous and healthy cells can reveal the genetic determinants of cancer. This knowledge results in a better understanding of the carcinogenic process and improved predictive power, with implications for identifying new drug targets, designing novel therapies, and improving preclinical and clinical studies. We review the concepts of biomarker, genetic marker, and genetic determinant in cancer, with particular focus on the most aggressive and lethal form of breast cancer, termed inflammatory breast cancer (IBC). Using IBC as an example, we describe in detail the approaches to identify the genes that are responsible for—and not merely associated with—this disease.
Adaptive Treatment Strategies in Chronic Disease
Authors: Lavori Philip W. , Dawson Ree
Published: October 2007

An adaptive treatment strategy (ATS) is a rule for adapting a treatment plan to a patient's history of previous treatments and the response to those treatments. The ongoing management of chronic disease defines an ATS, which may be implicit and hidden or explicit and well-specified. The ATS is characterized by the use of intermediate, early markers of response to dynamically alter treatment decisions, in order to achieve a favorable ultimate outcome. We illustrate the ATS concept and describe how the effect of initial treatment decisions depends on the performance of subsequent decisions at later stages. We show how to compare two or more ATSs, or to determine an optimal ATS, using a sequential multiple assignment randomized (SMAR) trial. Designers of clinical trials might find the ATS concept useful in improving the efficiency and ecological relevance of clinical trials.
Caveolae as Organizers of Pharmacologically Relevant Signal Transduction Molecules
Authors: Patel Hemal H. , Murray Fiona , Insel Paul A.
Published: October 2007

Caveolae, a subset of membrane (lipid) rafts, are flask-like invaginations of the plasma membrane that contain caveolin proteins, which serve as organizing centers for cellular signal transduction. Caveolins (-1, -2, and -3) have cytoplasmic N and C termini, palmitolylation sites, and a scaffolding domain that facilitates interaction and organization of signaling molecules so as to help provide coordinated and efficient signal transduction. Such signaling components include upstream entities (e.g., G protein–coupled receptors (GPCRs), receptor tyrosine kinases, and steroid hormone receptors) and downstream components (e.g., heterotrimeric and low-molecular-weight G proteins, effector enzymes, and ion channels). Diseases associated with aberrant signaling may result in altered localization or expression of signaling proteins in caveolae. Caveolin-knockout mice have numerous abnormalities, some of which may reflect the impact of total body knockout throughout the life span. This review provides a general overview of caveolins and caveolae, signaling molecules that localize to caveolae, the role of caveolae/caveolin in cardiac and pulmonary pathophysiology, pharmacologic implications of caveolar localization of signaling molecules, and the possibility that caveolae might serve as a therapeutic target.
Excitatory effects of synchronized intestinal electrical stimulation on small intestinal motility in dogs
Authors: Yin Jieyun , Chen Jiande DZ
Published: October 2007

The aim of this study was to investigate effects of synchronized intestinal electrical stimulation (SIES) on small intestinal motility in dogs. Seventeen dogs were equipped with a duodenal cannula for the measurement of small bowel motility using manometry; an additional cannula was equipped in six of the dogs with 1.5 m distal to the first one for the measurement of small intestinal transit. Two pairs of bipolar electrodes were implanted on the small intestinal serosa with an interval of 5 cm; glucagon was used to induce postprandial intestinal hypomotility. Eleven dogs were used for the assessment of the small intestinal contractions in both fasting and fed states. The other six dogs were used for the measurement of small intestinal transit. We found that 1) SIES induced small intestinal contractions during phase I of the migrating motor complex (MMC) (contractile index or CI: 5.2 ± 0.6 vs. 10.3 ± 0.7, P = 0.003); 2) in the fed state, SIES significantly improved glucagon-induced small intestinal postprandial hypomotility (CI: 3.4 ± 0.5 vs. 6.0 ± 0.3, P = 0.03); 3) SIES significantly accelerated small intestinal transit delayed by glucagon (70.4 ± 3.1 vs. 44.5 ± 3.1 min, P < 0.01); 4) there was a negative correlation between the CI and transit time ( r = −0.427, P = 0.048); and 5) the excitatory effect of SIES was blocked by atropine. SIES may have a therapeutic potential for treating patients with small intestinal disorders.
Opposite regulation of endothelial NO synthase by HSP90 and caveolin in liver and lungs of rats with hepatopulmonary syndrome
Authors: Frossard Jean-Louis , Schiffer Eduardo , Cikirikcioglu Banu , Bourquin Joëlle , Morel Denis R. , Pastor Catherine M.
Published: October 2007

The hepatopulmonary syndrome is a complication of cirrhosis that associates an overproduction of nitric oxide (NO) in lungs and a NO defect in the liver. Because endothelial NO synthase (eNOS) is regulated by caveolin that decreases and heat shock protein 90 (HSP90) that increases NO production, we hypothesized that an opposite regulation of eNOS by caveolin and HSP90 might explain the opposite NO production in both organs. Cirrhosis was induced by a chronic bile duct ligation (CBDL) performed 15, 30, and 60 days before sample collection and pharmacological tests. eNOS, caveolin, and HSP90 expression were measured in hepatic and lung tissues. Pharmacological tests to assess NO released by shear stress and by acetylcholine were performed in livers ( n = 28) and lungs ( n = 28) isolated from normal and CBDL rats. In lungs from CBDL rats, indirect evidence of high NO production induced by shear stress was associated with a high binding of HSP90 and a low binding of caveolin to eNOS. Opposite results were observed in livers from CBDL rats. Our study shows an opposite posttranslational regulation of eNOS by HSP90 and caveolin in lungs and liver from rats with CBDL. Such opposite posttranslational regulation of eNOS by regulatory proteins may explain in part the pulmonary overproduction of NO and the hepatic NO defect in rats with hepatopulmonary syndrome.
Early growth response-1 contributes to galactosamine/lipopolysaccharide-induced acute liver injury in mice
Authors: Pritchard Michele T. , Roychowdhury Sanjoy , McMullen Megan R. , Guo Luping , Arteel Gavin E. , Nagy Laura E.
Published: October 2007

Early growth response (Egr)-1 is a transcription factor that regulates genes involved in inflammation, innate and adaptive immunity, coagulation, and wound healing; however, little is known about the role of Egr-1 in acute liver injury. We tested the hypothesis that Egr-1 is involved in acute liver injury induced by galactosamine/lipopolysaccharide (GalN/LPS). GalN/LPS exposure biphasically increased hepatic egr-1 mRNA accumulation at 1 h and again at 4–5.5 h after treatment in wild-type mice. Within 4–5.5 h after GalN/LPS exposure, wild-type mice exhibited histological evidence of hepatocyte injury, cell death, and extensive areas of hemorrhage, as well as increased plasma alanine aminotransferase activities. In contrast, these parameters were largely attenuated in egr-1−/−mice. The initial expression of tumor necrosis factor-α, macrophage inflammatory protein-2, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1 mRNA or protein was equivalent between genotypes at 1 h after GalN/LPS administration. However, at subsequent time points, hepatic expression of these genes was decreased in egr-1−/−compared with wild-type mice. In addition, neutrophil extravasation from hepatic sinusoids into the liver parenchyma was decreased in egr-1−/−compared with wild-type mice 4 h after GalN/LPS. Whereas caspase-3 activation and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei were detected in wild-type mice at 4 and 5.5 h after GalN/LPS administration, respectively, these markers of apoptosis were delayed in egr-1−/−mice. Delayed development of apoptosis was associated with an extension of survival by 1 h in egr-1−/−compared with wild-type mice. These data demonstrate that Egr-1 plays an important role in acceleration of hepatic inflammation, apoptosis, and subsequent mortality in GalN/LPS-induced acute liver injury.
Inducible and myocyte-specific inhibition of PKCα enhances cardiac contractility and protects against infarction-induced heart failure
Authors: Hambleton Michael , York Allen , Sargent Michelle A. , Kaiser Robert A. , Lorenz John N. , Robbins Jeffrey , Molkentin Jeffery D.
Published: October 2007

Mice null for the gene encoding protein kinase Cα ( Prkca), or mice treated with pharmacologic inhibitors of the PKCα/β/γ isoforms, show an augmentation in cardiac contractility that appears to be cardioprotective. However, it remains uncertain if PKCα itself functions in a myocyte autonomous manner to affect cardioprotection in vivo. Here we generated cardiac myocyte-specific transgenic mice using a tetracycline-inducible system to permit controlled expression of dominant negative PKCα in the heart. Consistent with the proposed function of PKCα, induction of dominant negative PKCα expression in the adult heart enhanced baseline cardiac contractility. This increase in cardiac contractility was associated with a partial protection from long-term decompensation and secondary dilated cardiomyopathy after myocardial infarction injury. Similarly, Prkca null mice were also partially protected from infarction-induced heart failure, although the area of infarction injury was identical to controls. Thus, myocyte autonomous inhibition of PKCα protects the adult heart from decompensation and dilated cardiomyopathy after infarction injury in association with a primary enhancement in contractility.
Involvement of COX-1 in A3 adenosine receptor-mediated contraction through endothelium in mice aorta
Authors: Ansari Habib R. , Nadeem Ahmed , Tilley Stephen L. , Mustafa S. Jamal
Published: October 2007

We investigated whether A3 adenosine receptor (A3AR) is involved in endothelium-mediated contraction through cyclooxygenases (COXs) with the use of wild-type (WT) and A3 knockout (A3KO) mice aorta. A3AR-selective agonist, Cl-IBMECA, produced a concentration-dependent contraction (EC50: 2.9 ± 0.2 × 10−9 M) in WT mouse aorta with intact endothelium (+E) and negligible effects in A3KO +E aorta. At 10−7 M, contractions produced by Cl-IBMECA were 29% in WT +E, while being insignificant in A3KO +E aorta. Cl-IBMECA-induced responses were abolished in endothelium-denuded tissues (−E), in both WT and A3KO aorta. A3AR gene and protein expression were reduced by 74 and 72% ( P < 0.05), respectively, in WT −E compared with WT +E aorta, while being undetected in A3KO +E/−E aorta. Indomethacin (nonspecific COXs blocker, 10−5 M), SC-560 (specific COX-1 blocker, 10−8 M), SQ 29549 (thromboxane prostanoid receptor antagonist, 10−6 M), and furegrelate (thromboxane synthase inhibitor, 10−5 M) inhibited Cl-IBMECA-induced contraction significantly. Cl-IBMECA-induced thromboxane B2 production was also attenuated significantly by indomethacin, SC-560, and furegrelate in WT +E aorta, while having negligible effects in A3KO +E aorta. NS-398 (specific COX-2 blocker) produced negligible inhibition of Cl-IBMECA-induced contraction in both WT +E and A3KO +E aorta. Cl-IBMECA-induced increase in COX-1 and thromboxane prostanoid receptor expression were significantly inhibited by MRS1523, a specific A3AR antagonist in WT +E aorta. Expression of both A3AR and COX-1 was located mostly on endothelium of WT and A3KO +E aorta. These results demonstrate for the first time the involvement of COX-1 pathway in A3AR-mediated contraction via endothelium.
Temperature and state dependence of dynamic phrenic oscillations in the decerebrate juvenile rat
Authors: Marchenko Vitaliy , Rogers Robert F.
Published: October 2007

The aim of the present study was to determine characteristics of fast oscillations in the juvenile rat phrenic nerve (Ph) and to establish their temperature and state dependence. Two different age-matched decerebrate, baro- and chemodenervated rat preparations, in vivo and in situ arterially perfused models, were used to examine three systemic properties: 1) generation and dynamics of fast oscillations in Ph activity (both preparations), 2) responses to anoxia (both preparations), and 3) the effects of temperature on fast oscillations (in situ only). Both juvenile preparations generated power and coherence in two major bands analogous to adult medium- and high-frequency oscillations (HFO) at frequencies that increased with temperature but were lower than in adults. At < 28°C, however, Ph oscillations were confined primarily to one low-frequency band (20–45 Hz). During sustained anoxia, both preparations produced stereotypical state changes from eupnea to hyperpnea to transition bursting (a behavior present only in vivo during incomplete ischemia) to gasping. Thus the juvenile rat produces a sequential pattern of responses to anoxia that are intermediate forms between those produced by neonates and those produced by adults. Time-frequency analysis determined that fast oscillations demonstrated dynamics over the course of the inspiratory burst and a state dependence similar to that of adults in vivo in which hyperpnea (and transition) bursts are associated with increases in HFO, while gasping contains no HFO. Our results confirm that both the fast oscillations in Ph activity and the coherence between Ph pairs produced by the juvenile rat are profoundly state- and temperature-dependent.
Functional effects of nonsynonymous polymorphisms in the human TRPV1 gene
Authors: Xu Hongshi , Tian Wei , Fu Yi , Oyama Terry T. , Anderson Sharon , Cohen David M.
Published: October 2007

The prototypical member of the vanilloid-responsive-like subfamily of transient receptor potential (TRP) channels is TRPV1. TRPV1 mediates aspects of nociception and neurogenic inflammation; however, new roles are emerging in sensation of both luminal stretch and systemic tonicity. Although at least six nonsynonymous polymorphisms in the human TRPV1 gene have been identified, there has been no systematic investigation into their functional consequences. When heterologously expressed in HEK293 cells, all variants exhibited equivalent EC50 for the classic agonist capsaicin. This agonist elicited a greater maximal response in TRPV1I315M and TRPV1P91S variants (relative to TRPV1WT), as did a second agonist, anandamide. Expression of these two variants in whole-cell lysates and at the cell surface was markedly greater than that of wild-type TRPV1, whereas expression at the mRNA level was either unchanged (TRPV1P91S) or only very modestly increased (TRPV1I315M). Incorporation of multiple nonsynonymous SNPs, informed by the population-specific haplotype block structure of the TRPV1 gene, did not lead to variant channels with unique features vis-à-vis capsaicin responsiveness. Recently, polymorphisms/mutations were identified in two highly conserved TRPV1 residues in the nonobese diabetic (NOD) murine model. Incorporation of these changes into human TRPV1 gave rise to a channel with a normal EC50 for capsaicin, but with a markedly elevated Hill slope such that the variant channel was hyporesponsive to capsaicin at low doses (<10 nM) and hyperresponsive at high doses (>10 nM). In aggregate, these data underscore expression-level and functional differences among naturally occurring TRPV1 variants; the implications with respect to human physiology are considered.
TGF-β1and TNF-α are involved in the transcription of type I collagen α2gene in soleus muscle atrophied by mechanical unloading
Authors: Hirose Tatsuro , Nakazato Koichi , Song Hongsun , Ishii Naokata
Published: October 2007

The aim of this study was to examine the effect of hindlimb suspension (HS) on the expressions of COL1A2 (type I collagen α2chain) mRNA and its regulatory factors, transforming growth factors (TGF)-β1, -β2, and -β3, phosphorylated Smad3, and tumor necrosis factor-α (TNF-α) in rat hindlimb muscles. Forty-eight male Wistar rats (age, 5 wk) were randomly assigned to HS for 1, 3, 7, and 14 days and control ( n = 6 for each). During the exposure to HS, COL1A2 mRNA expression decreased in the soleus muscle at day 3 and recovered to control level at day 7. The content of TNF-α, one of the negative regulatory factors for COL1A2, increased from day 3 until day 14. On the other hand, the contents of TGF-β1, TGF-β3, and Smad3, positive regulatory factors for COL1A2, increased at day 7. The in situ hybridization for COL1A2 and the immunohistochemistry of TGF-β1and TNF-α revealed their expressions around nerve-related tissues, including muscle spindles and connective tissue sheath. The results indicate that the transcriptional activity of COL1A2 in the soleus muscle initially decreases in response to unloading through an increase in TNF-α production; thereafter, it returns toward normal level through the activated TGF-β/Smad pathway.
Muscle metabolic, SR Ca2+-cycling responses to prolonged cycling, with and without glucose supplementation
Authors: Duhamel T. A. , Green H. J. , Stewart R. D. , Foley K. P. , Smith I. C. , Ouyang J.
Published: October 2007

This study investigated the effects of prolonged exercise, with and without glucose supplementation, on metabolism and sarcoplasmic reticulum (SR) Ca2+-handling properties in working vastus lateralis muscle. Fifteen untrained volunteers [peak O2consumption (V̇o2peak) = 3.45 ± 0.17 l/min; mean ± SE] cycled at ∼60% V̇o2peakon two occasions, during which they were provided with either an artificially sweetened placebo beverage (NG) or a 6% glucose (G) beverage (∼1.00 g carbohydrate/kg body mass). Beverage supplementation started at 30 min of exercise and continued every 15 min thereafter. SR Ca2+handling, metabolic, and substrate responses were assessed in tissue extracted from the vastus lateralis at rest, after 30 min and 90 min of exercise, and at fatigue in both conditions. Plasma glucose during G was 15–23% higher ( P < 0.05) than those observed during NG following 60 min of exercise until fatigue. Cycle time to fatigue was increased ( P < 0.05) by ∼19% during G (137 ± 7 min) compared with NG (115 ± 6 min). Prolonged exercise reduced ( P < 0.05) maximal Ca2+-ATPase activity (−18.4%), SR Ca2+uptake (−27%), and both Phase 1 (−22.2%) and Phase 2 (−34.2%) Ca2+-release rates during NG. The exercise-induced reductions in SR Ca2+-cycling properties were not altered during G. The metabolic responses to exercise were all unaltered by glucose supplementation, since no differences in respiratory exchange ratios, carbohydrate and lipid oxidation rates, and muscle metabolite and glycogen contents were observed between NG and G. These results indicate that the maintenance of blood glucose homeostasis by glucose supplementation is without effect in modifying the muscle metabolic, endogenous glycogen, or SR Ca2+-handling responses.
Plasticity of the Synaptic Modification Range
Authors: Rioult-Pedotti M.-S. , Donoghue J. P. , Dunaevsky A.
Published: October 2007

Activity-dependent synaptic plasticity is likely to provide a mechanism for learning and memory. Cortical synaptic responses that are strengthened within a fixed synaptic modification range after 5 days of motor skill learning are driven near the top of their range, leaving only limited room for additional synaptic strengthening. If synaptic strengthening is a requisite step for acquiring new skills, near saturation of long-term potentiation (LTP) should impede further learning or the LTP mechanism should recover after single-task learning. Here we show that the initial learning-induced synaptic enhancement is sustained even long after training has been discontinued and that the synaptic modification range shifts upward. This range shift places increased baseline synaptic efficacy back within the middle of its operating range, allowing prelearning levels of LTP and long-term depression. Persistent synaptic strengthening might be a substrate for long-term retention in motor cortex, whereas the shift in synaptic modification range ensures the availability for new synaptic strengthening.
Activity of Murine Raphe Magnus Cells Predicts Tachypnea and On-Going Nociceptive Responsiveness
Authors: Hellman Kevin M. , Brink Thaddeus S. , Mason Peggy
Published: October 2007

In rats, opioids produce analgesia in large part by their effects on two cell populations in the medullary raphe magnus (RM). To extend our mechanistic understanding of opioid analgesia to the genetically tractable mouse, we characterized behavioral reactions and RM neural responses to opioid administration. d-Ala2, N-Me-Phe4-Gly5ol-enkephalin, a mu-opioid receptor agonist, microinjected into the murine RM produced cardiorespiratory depression and reduced slow wave electroencephalographic activity as well as increased the noxious heat-evoked withdrawal latencies. As in rat, RM cell types that were excited and inhibited by noxious stimuli, termed on and off cells, respectively, were observed in mice. However, in contrast to findings in rat, opioid doses that suppressed withdrawals did not alter the background discharge rate of murine on and off cells, suggesting that the cellular mechanisms by which the murine RM generates opioid analgesia are substantially different from those in rats. Murine on cell discharge did not predict the latency or magnitude of an ensuing withdrawal but did correlate to the magnitude and latency of concurrent withdrawals. Although opioids failed to alter the background discharge of on and off cells, they reduced the responses of RM neurons to noxious stimulation, further evidence that RM modulates on-going withdrawals. In characterizing the role of RM in respiratory modulation, we found that on cells burst and off cells paused during tachypneic events. The effects of opioids in the murine RM on homeostasis and the association of on and off cell discharge with tachypnea corroborate roles for opioid signaling in RM beyond analgesia.