bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid radiographic film calibration for IMRT verification using automated MLC fields
Authors: Childress Nathan L. , Dong Lei , Rosen Isaac I.
Published: November 2002

A method for measuring a film sensitometric curve using a single sheet of film exposed with a two field step‐and‐shoot MLC treatment was developed and tested with Kodak XV2 and EDR2 films. With this technique a film sensitometric curve can be completed in only 10 minutes, making it practical to generate new film calibrations daily. This method is applicable to film calibrations for all purposes, but is particularly useful in IMRT treatment verification due to the method's use of small fields. This method agrees with the traditional large‐field multifilm calibration within 0.5% and will produce sensitometric curves with errors less than 1% throughout the dose range, including uncertainties in dose delivery, film response, and optical density measurements. OD values for XV2 and EDR2 films were consistent in the middle of exposure areas at high depths, but the XV2 film penumbra regions showed large amounts of over‐response as the calibration depth increased. If XV2 film is used for IMRT treatment verification, it is necessary to reduce the fluence of low energy photons in areas around the film by using thin lead shields. EDR2 film was shown to have minimal energy dependence, as it accurately represented penumbra areas and yielded identical sensitometric curves generated with 6 and 18 MV photons. However, its darker tint may make it more sensitive to scanning laser film digitizers' horizontal nonuniformities. This single film method proved to be superior to the traditional calibration method and allows fast daily calibrations of films for highly accurate IMRT delivery verifications.
Pathophysiological effects of radiation on atherosclerosis development and progression, and the incidence of cardiovascular complications
Authors: Basavaraju Sekhara Rao , Easterly Clay E.
Published: November 2002

Radiation therapy while important in the management of several diseases, is implicated in the causation of atherosclerosis and other cardiovascular complications. Cancer and atherosclerosis go through the same stages of initiation, promotion, and complication, beginning with a mutation in a single cell. Clinical observations before the 1960s lead to the belief that the heart is relatively resistant to the doses of radiation used in radiotherapy. Subsequently, it was discovered that the heart is sensitive to radiation and many cardiac structures may be damaged by radiation exposure. A significantly higher risk of death due to ischemic heart disease has been reported for patients treated with radiation for Hodgkin's disease and breast cancer. Certain cytokines and growth factors, such as TGF‐β1 and IL‐1 β, may stimulate radiation‐induced endothelial proliferation, fibroblast proliferation, collagen deposition, and fibrosis leading to advanced lesions of atherosclerosis. The treatment for radiation‐induced ischemic heart disease includes conventional pharmacological therapy, balloon angioplasty, and bypass surgery. Endovascular irradiation has been shown to be effective in reducing restenosis‐like response to balloon‐catheter injury in animal models. Caution must be exercised when radiation therapy is combined with doxorubicin because there appears to be a synergistic toxic effect on the myocardium. Damage to endothelial cells is a central event in the pathogenesis of damage to the coronary arteries. Certain growth factors that interfere with the apoptotic pathway may provide new therapeutic strategies for reducing the risk of radiation‐induced damage to the heart. Exposure to low level occupational or environmental radiation appears to pose no undue risk of atherosclerosis development or cardiovascular mortality. But, other radiation‐induced processes such as the bystander effects, abscopal effects, hormesis, and individual variations in radiosensitivity may be important in certain circumstances.
Prospects for quantitative computed tomography imaging in the presence of foreign metal bodies using statistical image reconstruction
Authors: Williamson Jeffrey F. , Whiting Bruce R. , Benac Jasenka , Murphy Ryan J. , Blaine G. James , O'Sullivan Joseph A. , Politte David G. , Snyder Donald L.
Published: November 2002

X‐ray computed tomography (CT) images of patients bearing metal intracavitary applicators or other metal foreign objects exhibit severe artifacts including streaks and aliasing. We have systematically evaluated via computer simulations the impact of scattered radiation, the polyenergetic spectrum, and measurement noise on the performance of three reconstruction algorithms: conventional filtered backprojection (FBP), deterministic iterative deblurring, and a new iterative algorithm, alternating minimization (AM), based on a CT detector model that includes noise, scatter, and polyenergetic spectra. Contrary to the dominant view of the literature, FBP streaking artifacts are due mostly to mismatches between FBP's simplified model of CT detector response and the physical process of signal acquisition. Artifacts on AM images are significantly mitigated as this algorithm substantially reduces detector‐model mismatches. However, metal artifacts are reduced to acceptable levels only when prior knowledge of the metal object in the patient, including its pose, shape, and attenuation map, are used to constrain AM's iterations. AM image reconstruction, in combination with object‐constrained CT to estimate the pose of metal objects in the patient, is a promising approach for effectively mitigating metal artifacts and making quantitative estimation of tissue attenuation coefficients a clinical possibility.
Controllability of depth dose distribution for neutron capture therapy at the Heavy Water Neutron Irradiation Facility of Kyoto University Research Reactor
Authors: Sakurai Yoshinori , Kobayashi Tooru
Published: November 2002

The updating construction of the Heavy Water Neutron Irradiation Facility of the Kyoto University Research Reactor has been performed from November 1995 to March 1996 mainly for the improvement in neutron capture therapy. On the performance, the neutron irradiation modes with the variable energy spectra from almost pure thermal to epi‐thermal neutrons became available by the control of the heavy‐water thickness in the spectrum shifter and by the open‐and‐close of the cadmium and boral thermal neutron filters. The depth distributions of thermal, epi‐thermal and fast neutron fluxes were measured by activation method using gold and indium, and the depth distributions of gamma‐ray absorbed dose rate were measured using thermo‐luminescent dosimeter of beryllium oxide for the several irradiation modes. From these measured data, the controllability of the depth dose distribution using the spectrum shifter and the thermal neutron filters was confirmed.
Development of contrast digital mammography
Authors: Skarpathiotakis Mia , Yaffe Martin J. , Bloomquist Aili K. , Rico Dan , Muller Serge , Rick Andreas , Jeunehomme Fanny
Published: November 2002

Development of breast tumors is often accompanied by angiogenesis—the formation of new blood vessels. It is possible to image the effects of this process by tracking the uptake and washout of contrast agents in the vicinity of a lesion. In this article, a method for carrying out contrast subtraction mammography on a full‐field digital mammography unit is described. Spectral measurements and modeling were performed to optimize the choice of x‐ray target, kilovoltage and x‐ray beam filtration for contrast digital mammography (CDM) on an available digital mammography system. Phantom studies were carried out to determine the sensitivity of CDM to iodine. Detection of iodine area densities of 0.3 mg/cm2 is possible for a circular object with a radius of 1.3 mm, which allows detection of uptake levels in the breast typically seen with cancer and some benign breast conditions. It was found that with a molybdenum anode x‐ray tube, copper filtration could be used to effectively shape the x‐ray spectrum to maximize the proportion of x rays with energies above the k edge of iodine. Simple logarithmic subtraction was found to be adequate in suppressing background signals dependent on the x‐ray beam intensity and background thickness of the breast. The total x‐ray dose from the procedure ranges between 1 and 3 mGy, similar to that from a conventional single view film mammogram. A clinical pilot study is currently being carried out to evaluate this technique.
Attenuation of 4–20 MV x rays by a new compensator material of cement
Authors: Thomsen Mette S. , Ulsø Niels
Published: November 2002

The properties of a new cement based material for production of compensators are presented. Broad beam attenuation of 4–20 MV x rays by slabs of the material have been measured at various field sizes and depths in a large water phantom. For comparison the attenuation of aluminum was determined at some of the photon energies and it was found that the attenuation properties of the cement based material are very close to those of aluminum. At 6 and 18 MV, a comparison of different phantoms for attenuation measurements was carried out. For this investigation the ionization chamber was placed in a 50×50×50 water phantom, a 20×20×20 water equivalent plastic phantom, and a cylindrical mini‐phantom. Agreement was obtained between the measurements in the large water phantom and in the water equivalent plastic phantom. The measurements carried out with the mini‐phantom in a 6 MV x‐ray beam gave a higher transmission versus absorber thickness than the transmission found with the water phantom resulting in a lower value of the effective attenuation coefficient. At 18 MV x rays the difference between the measurements in the water phantom and in the mini‐phantom was less. This shows that a water equivalent plastic phantom with an area comparable with the largest field size applied can be used for measurements of effective attenuation coefficients, whereas a mini‐phantom cannot be used directly, especially at low photon energies.
Experimental determination of dosimetric characterization of a newly designed encapsulated interstitial brachytherapy source of ‐model Pd‐1
Authors: Nath Ravinder , Yue Ning , Roa Eduardo
Published: November 2002

A newly designed encapsulated source has been introduced (BrachySeed™‐Pd‐103, also named Model Pd‐1, manufactured by DRAXIMAGE Inc. and distributed by Cytogen Corp.) for interstitial brachytherapy to provide more isotropic dose distributions. In this work, the dosimetric characteristics of the source were measured with micro LiF TLD chips and dosimetry parameters were characterized based upon the American Association of Physicists in Medicine (AAPM) Task Group No. 43 formalism. The dose rate constant of the sources was determined to be 0.66±0.05 cGy h−1 U−1. The radial dose function was measured and was found to be similar to that of the Theragenics Model 200 source. The anisotropy constant for the Model Pd‐1 source was determined to be 1.03.
Studies on a computer‐aided sketch drawing and similarity‐based retrieval in medical images (in Japanese)
Authors: Nakagawa Toshiaki
Published: November 2002

In this thesis a computer‐aided sketch (CAS) system and a similarity‐based retrieval method in medical images are proposed. A CAS system was developed for assisting physicians to draw a sketch when they were reading a mammogram. The sketch is automatically drawn using elements in the mammogram that were extracted by automated detection techniques developed in our computer‐aided diagnosis (CAD) research. In the thesis a technique is described for the segmentation of pectoral‐muscle regions for the CAD and CAS systems. The pectoral‐muscle region was determined from an edge‐enhanced image obtained with a Prewitt filter by searching for a boundary between the pectoral‐muscle region and mammary region. The boundaries were extracted correctly in 502 out of 513 images. In the thesis the CAS system is described. Its performance was evaluated by comparing its sketches of mammograms to those made by a physician. 430 mammograms were used in this study. Some differences in the sketches made by the physician and CAS system from the same mammogram are illustrated. If the contours of masses were clear, the sketches tended to match well to the physician's. A method of similarity‐based image retrieval and demonstrations of its potential usefulness for medical images is described. The purpose was to develop an image retrieval system that searches the image database for an image resembling the one entered without carrying out image segmentation. The approach presented includes a local‐pattern matching method and principal component analysis on monochromatic images. The image retrieval method was able to find images with similar characteristics from 30 monochromatic images. Initial results on mammographic masses indicate that the method might provide a new CAD system for mammograms.
Spot scanning using radioactive beams for heavy–ion radiotherapy (in Japanese)
Authors: Urakabe Eriko
Published: November 2002

In this thesis we describe a technique for determining the spatial distribution of beams at the Heavy Ion Medical Accelerator in Chiba (HIMAC). A narrow beam of ions will be moved to various positions to irradiate a three‐dimensional conformal field in a patient body. Since is a positron emitter, one can determine the spatial distribution of where the ions terminated with a PET scanner. The intensity of the beam is less than 1% of the beam. We used the more efficient spot scanning for the dose delivery. The spot beam of (346 MeV/n) is produced by a projectile‐fragmentation process of accelerated (430 MeV/n) beams in a Be target 51 mm in thickness. The depth and lateral size of the spot beam are chosen by selection of its momentum and focusing, respectively. In order to deliver the desired dose to the irradiation volume, the depth dose and lateral dose distribution of the spot beam were corrected by taking into consideration its wide momentum spread (2%). A spot beam consists of monochromatic beam fractions of various momenta, which lead to various ranges. Each beam fraction has a different lateral beam size because of an aberration of the lens system used in beam delivery. The dose distribution is measured by a multistrip parallel‐plate ionization chamber by changing the thickness of upstream PMMA slabs. The calculated dose distribution of the irradiation volume of in the PMMA phantom of was in good agreement (±0.2%) with measurements.
Containing Bioterrorist Smallpox
Authors: Halloran M. Elizabeth , Longini Ira M. , Nizam Azhar , Yang Yang
Published: November 2002

The need for a planned response to a deliberate introduction of smallpox has recently become urgent. We constructed a stochastic simulator of the spread of smallpox in structured communities to compare the effectiveness of mass vaccination versus targeted vaccination of close contacts of cases. Mass vaccination before smallpox introduction or immediately after the first cases was more effective than targeted vaccination in preventing and containing epidemics if there was no prior herd immunity (that is, no prior immunologic protection within the population). The effectiveness of postrelease targeted and mass vaccinations increased if we assumed that there was residual immunity in adults vaccinated before 1972, but the effectiveness of targeted vaccination increased more than that of mass vaccination. Under all scenarios, targeted vaccination prevented more cases per dose of vaccine than did mass vaccination. Although further research with larger-scale structured models is needed, our results suggest that increasing herd immunity, perhaps with a combination of preemptive voluntary vaccination and vaccination of first responders, could enhance the effectiveness of postattack intervention. It could also help targeted vaccination be more competitive with mass vaccination at both preventing and containing a deliberate introduction of smallpox.
Viral IL-6-Induced Cell Proliferation and Immune Evasion of Interferon Activity
Authors: Chatterjee Malini , Osborne Julie , Bestetti Giovanna , Chang Yuan , Moore Patrick S.
Published: November 2002

Lymphoma cells infected with Kaposi's sarcoma–associated herpesvirus are autocrine dependent on virus-derived interleukin-6 (IL-6), but not on cellular IL-6. During viral infection, host cells induce the antiviral factor interferon (IFN) to up-regulate p21, initiate cell cycle arrest, and inhibit virus replication. Viral IL-6, however, blocks IFN signaling. A viral transcriptional program exists in which only the viral IL-6 gene is directly activated by IFN-α, allowing the virus to modify its cellular environment by sensing and responding to levels of intracellular IFN signaling. The human cytokine cannot mimic this effect because IFN-α down-regulates the IL-6 receptor, gp80. Viral IL-6 bypasses the gp80 regulatory checkpoint by binding directly to the gp130 transducer molecule, resulting in tumor cell autocrine dependence on the viral cytokine for proliferation and survival.
Projection of an Immunological Self Shadow Within the Thymus by the Aire Protein
Authors: Anderson Mark S. , Venanzi Emily S. , Klein Ludger , Chen Zhibin , Berzins Stuart P. , Turley Shannon J. , von Boehmer Harald , Bronson Roderick , Dierich Andrée , Benoist Christophe , Mathis Diane
Published: November 2002

Humans expressing a defective form of the transcription factor AIRE (autoimmune regulator) develop multiorgan autoimmune disease. We used
aire
- deficient mice to test the hypothesis that this transcription factor regulates autoimmunity by promoting the ectopic expression of peripheral tissue– restricted antigens in medullary epithelial cells of the thymus. This hypothesis proved correct. The mutant animals exhibited a defined profile of autoimmune diseases that depended on the absence of aire in stromal cells of the thymus. Aire-deficient thymic medullary epithelial cells showed a specific reduction in ectopic transcription of genes encoding peripheral antigens. These findings highlight the importance of thymically imposed “central” tolerance in controlling autoimmunity.
Transition State Stabilization by a Catalytic RNA
Authors: Rupert Peter B. , Massey Archna P. , Sigurdsson Snorri Th. , Ferré-D'Amaré Adrian R.
Published: November 2002

The hairpin ribozyme catalyzes sequence-specific cleavage of RNA through transesterification of the scissile phosphate. Vanadate has previously been used as a transition state mimic of protein enzymes that catalyze the same reaction. Comparison of the 2.2 angstrom resolution structure of a vanadate–hairpin ribozyme complex with structures of precursor and product complexes reveals a rigid active site that makes more hydrogen bonds to the transition state than to the precursor or product. Because of the paucity of RNA functional groups capable of general acid-base or electrostatic catalysis, transition state stabilization is likely to be an important catalytic strategy for ribozymes.
53BP1, a Mediator of the DNA Damage Checkpoint
Authors: Wang Bin , Matsuoka Shuhei , Carpenter Phillip B. , Elledge Stephen J.
Published: November 2002

53BP1 binds to the tumor suppressor protein p53 and has a potential role in DNA damage responses. We used small interfering RNA (siRNA) directed against 53BP1 in mammalian cells to demonstrate that 53BP1 is a key transducer of the DNA damage checkpoint signal. 53BP1 was required for p53 accumulation, G
2
-M checkpoint arrest, and the intra-S-phase checkpoint in response to ionizing radiation. 53BP1 played a partially redundant role in phosphorylation of the downstream checkpoint effector proteins Brca1 and Chk2 but was required for the formation of Brca1 foci in a hierarchical branched pathway for the recruitment of repair and signaling proteins to sites of DNA damage.
On the Origin of Interictal Activity in Human Temporal Lobe Epilepsy in Vitro
Authors: Cohen Ivan , Navarro Vincent , Clemenceau Stéphane , Baulac Michel , Miles Richard
Published: November 2002

The origin and mechanisms of human interictal epileptic discharges remain unclear. Here, we describe a spontaneous, rhythmic activity initiated in the subiculum of slices from patients with temporal lobe epilepsy. Synchronous events were similar to interictal discharges of patient electroencephalograms. They were suppressed by antagonists of either glutamatergic or γ-aminobutyric acid (GABA)–ergic signaling. The network of neurons discharging during population events comprises both subicular interneurons and a subgroup of pyramidal cells. In these pyramidal cells, GABAergic synaptic events reversed at depolarized potentials. Depolarizing GABAergic responses in neurons downstream to the sclerotic CA1 region contribute to human interictal activity.
Unbalanced Bounty from America's Farms
Authors: Timmer C. Peter
Published: November 2002

American Agriculture in the Twentieth Century
. How It Flourished and What It Cost. Bruce L. Gardner. Harvard University Press, Cambridge, MA, 2002. 400 pp. $49.95, £33.50, €49.95. ISBN 0-674-00748-4.

Gardner surveys the challenges faced by U.S. farmers and the technological and economic transformations they have experienced over the past century. He finds that government actions have played a particularly important role.
Molecule Cascades
Authors: Heinrich A. J. , Lutz C. P. , Gupta J. A. , Eigler D. M.
Published: November 2002

Carbon monoxide molecules were arranged in atomically precise configurations, which we call “molecule cascades,” where the motion of one molecule causes the subsequent motion of another, and so on in a cascade of motion similar to a row of toppling dominoes. Isotopically pure cascades were assembled on a copper (111) surface with a low-temperature scanning tunneling microscope. The hopping rate of carbon monoxide molecules in cascades was found to be independent of temperature below 6 kelvin and to exhibit a pronounced isotope effect, hallmarks of a quantum tunneling process. At higher temperatures, we observed a thermally activated hopping rate with an anomalously low Arrhenius prefactor that we interpret as tunneling from excited vibrational states. We present a cascade-based computation scheme that has all of the devices and interconnects required for the one-time computation of an arbitrary logic function. Logic gates and other devices were implemented by engineered arrangements of molecules at the intersections of cascades. We demonstrate a three-input sorter that uses several AND gates and OR gates, as well as the crossover and fan-out units needed to connect them.
Critical Roles of Activation-Induced Cytidine Deaminase in the Homeostasis of Gut Flora
Authors: Fagarasan Sidonia , Muramatsu Masamichi , Suzuki Keiichiro , Nagaoka Hitoshi , Hiai Hiroshi , Honjo Tasuku
Published: November 2002

Activation-induced cytidine deaminase (AID) plays an essential role in class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes. We report here that deficiency in AID results in the development of hyperplasia of isolated lymphoid follicles (ILFs) associated with a 100-fold expansion of anaerobic flora in the small intestine. Reduction of bacterial flora by antibiotic treatment of AID
−/−
mice abolished ILF hyperplasia as well as the germinal center enlargement seen in secondary lymphoid tissues. Because an inability to switch to immunoglobulin A on its own does not lead to a similar phenotype, these results suggest that SHM of ILF B cells plays a critical role in regulating intestinal microflora.
Broadband Modulation of Light by Using an Electro-Optic Polymer
Authors: Lee Mark , Katz Howard E. , Erben Christoph , Gill Douglas M. , Gopalan Padma , Heber Joerg D. , McGee David J.
Published: November 2002

A major challenge to increasing bandwidth in optical telecommunications is to encode electronic signals onto a lightwave carrier by modulating the light up to very fast rates. Polymer electro-optic materials have the necessary properties to function in photonic devices beyond the 40-GHz bandwidth currently available. An appropriate choice of polymers is shown to effectively eliminate the factors contributing to an optical modulator's decay in the high-frequency response. The resulting device modulates light with a bandwidth of 150 to 200 GHz and produces detectable modulation signal at 1.6 THz. These rates are faster than anticipated bandwidth requirements for the foreseeable future.
Requirement of Hos2 Histone Deacetylase for Gene Activity in Yeast
Authors: Wang Amy , Kurdistani Siavash K. , Grunstein Michael
Published: November 2002

Histone deacetylases, typified by class I Rpd3 in the yeast
Saccharomyces cerevisiae
, have historically been associated with gene repression. We now demonstrate that Hos2, another member of the class I family, binds to the coding regions of genes primarily during gene activation, when it specifically deacetylates the lysines in H3 and H4 histone tails. Moreover, Hos2 is preferentially associated with genes of high activity genome-wide. We also show that Hos2 and an associated factor, Set3, are necessary for efficient transcription. Therefore, our data indicate that, in contrast to other class I histone deacetylases, Hos2 is directly required for gene activation.
Some GM Facts
Authors: Tester Mark
Published: November 2002

High Tech Harvest
. Understanding Genetically Modified Food Plants. Paul F. Lurquin. Westview (Perseus), Boulder, CO, 2002. 236 pp., illus. $25, C$37.95. ISBN 0-8133-3946-4.

Lurquin offers the general public a summary of the science behind genetically engineered plants and a discussion of their potential applications.
Spontaneous Bose Coherence of Excitons and Polaritons
Authors: Snoke David
Published: November 2002

In the past decade, there has been an increasing number of experiments on spontaneous Bose coherence of excitons and polaritons. Four major areas of research are reviewed here: three-dimensional excitons in the bulk semiconductor Cu
2
O, two-dimensional excitons in coupled quantum wells, Coulomb drag experiments in coupled two-dimensional electron gases, and polaritons in semiconductor microcavities. The unifying theory of all these experiments is the effect of spontaneous symmetry breaking in the Bose-Einstein condensation phase transition.
Structure of a Langmuir Film on a Liquid Metal Surface
Authors: Kraack H. , Ocko B. M. , Pershan P. S. , Sloutskin E. , Deutsch M.
Published: November 2002

The structure of organic monolayers on liquid surfaces depends sensitively on the details of the molecular interactions. The structure of a stearic acid film on a mercury surface was measured as a function of coverage with angstrom resolution. Unlike monolayers on water, the molecules were found here to undergo a transition from surface-parallel to surface-normal orientation with increasing coverage. At high coverage, two condensed hexatic phases of standing-up molecules were found. At low coverage, a two-dimensional (2D) gas phase and condensed single- and double-layered phases of flat-lying molecular dimers were revealed, exhibiting a 1D longitudinal positional order. This system should provide a broader tunability range for nanostructure construction than solid-supported self-assembled monolayers.
Cavity Quantum Electrodynamics: Coherence in Context
Authors: Mabuchi H. , Doherty A. C.
Published: November 2002

Modern cavity quantum electrodynamics (cavity QED) illuminates the most fundamental aspects of coherence and decoherence in quantum mechanics. Experiments on atoms in cavities can be described by elementary models but reveal intriguing subtleties of the interplay of coherent dynamics with external couplings. Recent activity in this area has pioneered powerful new approaches to the study of quantum coherence and has fueled the growth of quantum information science. In years to come, the purview of cavity QED will continue to grow as researchers build on a rich infrastructure to attack some of the most pressing open questions in micro- and mesoscopic physics.
Coherent Optical Information Systems
Authors: Psaltis Demetri
Published: November 2002

Coherent optical beams are used to communicate, store, and process information in a growing number of applications. The availability of coherent laser sources is of critical importance for the realization of such optical information systems. An incoherent source randomly populates the available temporal and spatial channels of the optical system, making it difficult to represent information. Coherent laser sources provide a stable carrier on which to encode information, making it possible to realize powerful information-processing techniques such as wavelength division multiplexing in fiber networks, gated holographic imaging, and three-dimensional optical data storage.
Coherence with Atoms
Authors: Kasevich Mark A.
Published: November 2002

The past decade has seen dramatic progress in our ability to manipulate and coherently control the motion of atoms. This progress has both fundamental and applied importance. On the one hand, recent experiments are providing new perspectives for the study of quantum phase transitions and highly entangled quantum states. On the other hand, this exquisite control offers the prospect of a new generation of force sensors of unprecedented sensitivity and accuracy.
A CLASS OF IRREDUNDANT ENCODING TECHNIQUES FOR REDUCING BUS POWER
Authors: AGHAGHIRI YAZDAN , FALLAH FARZAN , PEDRAM MASSOUD
Published: November 2002

This paper proposes a number of encoding techniques for decreasing power dissipation on global buses. The best target for these techniques is a wide and highly capacitive memory bus. Switching activity of the bus is reduced by means of encoding the values that are conveyed over them. More precisely, three irredundant bus-encoding techniques are presented in this paper. These techniques decrease the bus activity by as much as 86% for instruction addresses without the need to add redundant bus lines. Having no redundancy means that exercising these techniques on any existing system does not require redesign and remanufacturing of the printed circuit board of the system. The power dissipation of the encoder and decoder blocks is insignificant in comparison with the power saved on the memory address bus. This makes these techniques capable of reducing the total power consumption.
THE IMPACT OF SOURCE CODE TRANSFORMATIONS ON SOFTWARE POWER AND ENERGY CONSUMPTION
Authors: BRANDOLESE CARLO , FORNACIARI WILLIAM , SALICE FABIO , SCIUTO DONATELLA
Published: November 2002

Software power consumption minimization is increasingly a very relevant issue in the design of embedded systems, in particular those dedicated to mobile devices. The paper aims to review the state of the art source code transformations in terms of their effectiveness on power and energy consumption reduction. A design framework for the C language has been set up, using the gcc compiler with SimplePower as the simulation kernel. Some new transformations have also been identified with the aim of reducing the power consumption. Four classes of transformations will be considered: loop transformations, data structures transformations, inter-procedural transformations and control structure transformations. For each transformation, together with the evaluation of the energy and power consumption, some applicability criteria have been defined.
USING MEMORY COMPRESSION FOR ENERGY REDUCTION IN AN EMBEDDED JAVA SYSTEM
Authors: CHEN G. , KANDEMIR M. , VIJAYKRISHNAN N. , IRWIN M. J. , WOLF W.
Published: November 2002

The Java programming language is being increasingly used for application development for mobile and embedded devices. Limited energy and memory resources are important constraints for such systems. Compression is an useful and widely employed mechanism to reduce the memory requirements of the system. As the leakage energy of a memory system increases with its size and because of the increasing contribution of leakage to overall system energy, compression also has a significant effect on reducing energy consumption. However, storing compressed data/instructions has a performance and energy overhead associated with decompression at runtime. The underlying compression algorithm, the corresponding implementation of the decompression and the ability to reuse decompressed information critically impact this overhead.

In this paper, we explore the influence of compression on overall memory energy using a commercial embedded Java virtual machine (JVM) and a customized compression algorithm. Our results show that compression is effective in reducing energy even when considering the runtime decompression overheads for most applications. Further, we show a mechanism that selectively compresses portions of the memory to enhance energy savings. Finally, a scheme for clustering the code and data to improve the reuse of the decompressed data is presented.
NOISE IMPROVEMENTS IN STOCHASTIC RESONANCE: FROM SIGNAL AMPLIFICATION TO OPTIMAL DETECTION
Authors: CHAPEAU-BLONDEAU FRANÇOIS , ROUSSEAU DAVID
Published: November 2002

It is demonstrated that benefits from the noise can be gained at various levels in stochastic resonance. Raising the noise can produce signal amplification as well as signal-to-noise ratio improvement, input–output gain exceeding unity in signal-to-noise ratio, and enhanced performance in optimal processing. This series of benefits is successively exhibited in the processing of a periodic signal coupled to a white noise through essentially static nonlinearities. Especially, it is established that noise benefits in stochastic resonance can extend up to optimal processing, by considering an optimal Bayesian detector whose performance is improvable by raising the level of the noise.
Mechanical Signaling and the Cellular Response to Extracellular Matrix in Angiogenesis and Cardiovascular Physiology
Authors: Ingber Donald E.
Published: November 2002

Great advances have been made in the identification of the soluble angiogenic factors, insoluble extracellular matrix (ECM) molecules, and receptor signaling pathways that mediate control of angiogenesis—the growth of blood capillaries. This review focuses on work that explores how endothelial cells integrate these chemical signals with mechanical cues from their local tissue microenvironment so as to produce functional capillary networks that exhibit specialized form as well as function. These studies have revealed that ECM governs whether an endothelial cell will switch between growth, differentiation, motility, or apoptosis programs in response to a soluble stimulus based on its ability to mechanically resist cell tractional forces and thereby produce cell and cytoskeletal distortion. Transmembrane integrin receptors play a key role in this mechanochemical transduction process because they both organize a cytoskeletal signaling complex within the focal adhesion and preferentially focus mechanical forces on this site. Molecular filaments within the internal cytoskeleton—microfilaments, microtubules, and intermediate filaments—also contribute to the cell’s structural and functional response to mechanical stress through their role as discrete support elements within a tensegrity-stabilized cytoskeletal array. Importantly, a similar form of mechanical control also has been shown to be involved in the regulation of contractility in vascular smooth muscle cells and cardiac myocytes. Thus, the mechanism by which cells perform mechanochemical transduction and the implications of these findings for morphogenetic control are discussed in the wider context of vascular development and cardiovascular physiology.
Structure of Cerebral Arterioles in Cystathionine β-Synthase-Deficient Mice
Authors: Baumbach Gary L. , Sigmund Curt D. , Bottiglieri Teodoro , Lentz Steven R.
Published: November 2002

We examined effects of hyperhomocysteinemia on structure and mechanics of cerebral arterioles. We measured plasma total homocysteine (tHcy) and pressure, diameter, and cross-sectional area of the vessel wall in maximally dilated cerebral arterioles in heterozygous cystathionine β-synthase-deficient (CBS
+/−
) mice and wild-type (CBS
+/+
) littermates that were provided with drinking water that was unsupplemented (control diet) or supplemented with 0.5%
l
-methionine (high-methionine diet). Plasma tHcy was 5.0±1.1 μmol/L in CBS
+/+
mice and 8.3±0.9 μmol/L in CBS
+/−
mice (
P
<0.05 versus CBS
+/+
mice) fed the control diet. Plasma tHcy was 17.2±4.6 μmol/L in CBS
+/+
mice and 21.2±3.9 μmol/L in CBS
+/−
mice (
P
<0.05) fed the high-methionine diet. Cross-sectional area of the vessel wall was significantly increased in CBS
+/−
(437±22 μm
2
) mice fed control diet and CBS
+/+
(442±36 μm
2
) and CBS
+/−
(471±46 μm
2
) mice fed high-methionine diet relative to CBS
+/+
(324±18 μm
2
) mice fed control diet (
P
<0.05). During maximal dilatation, the stress-strain curves in cerebral arterioles of CBS
+/−
mice on control diet and CBS
+/+
and CBS
+/−
mice on high-methionine diet were shifted to the right of the curve in cerebral arterioles of CBS
+/+
mice on control diet, an indication that distensibility of cerebral arterioles was increased in mice with elevated levels of plasma tHcy. Thus, hyperhomocysteinemia in mice was associated with hypertrophy and an increase in distensibility of cerebral arterioles. These findings suggest that hyperhomocysteinemia promotes cerebral vascular hypertrophy and altered cerebral vascular mechanics, both of which may contribute to the increased incidence of stroke associated with hyperhomocysteinemia.
Gene Transfer of the Urokinase-Type Plasminogen Activator Receptor-Targeted Matrix Metalloproteinase Inhibitor TIMP-1.ATF Suppresses Neointima Formation More Efficiently Than Tissue Inhibitor of Metalloproteinase-1
Authors: Lamfers M.L.M. , Grimbergen J.M. , Aalders M.C. , Havenga M.J. , de Vries M.R. , Huisman L.G.M. , van Hinsbergh V.W.M. , Quax P.H.A.
Published: November 2002

Proteases of the plasminogen activator (PA) and matrix metalloproteinase (MMP) system play an important role in smooth muscle cell (SMC) migration and neointima formation after vascular injury. Inhibition of either PAs or MMPs has previously been shown to result in decreased neointima formation in vivo. To inhibit both protease systems simultaneously, a novel hybrid protein, TIMP-1.ATF, was constructed consisting of the tissue inhibitor of metalloproteinase-1 (TIMP-1) domain, as MMP inhibitor, linked to the receptor-binding amino terminal fragment (ATF) of urokinase. By binding to the u-PA receptor this protein will not only anchor the TIMP-1 moiety directly to the cell surface, it will also prevent the local activation of plasminogen by blocking the binding of urokinase-type plasminogen activator (u-PA) to its receptor. Adenoviral expression of TIMP-1.ATF was used to inhibit SMC migration and neointima formation in human saphenous vein segments in vitro. SMC migration was inhibited by 65% in Ad.TIMP-1.ATF-infected cells. Infection with adenoviral vectors encoding the individual domains, Ad.TIMP-1 and Ad.ATF, reduced migration by 32% and 52%, respectively. Neointima formation in saphenous vein organ cultures infected with Ad.TIMP-1.ATF was inhibited by 72% compared with 42% reduction after Ad.TIMP-1 infection and 34% after Ad.ATF infection. These data show that binding of TIMP-1.ATF hybrid protein to the u-PA receptor at the cell surface strongly enhances the inhibitory effect of TIMP-1 on neointima formation in human saphenous vein cultures.
Derivation and Potential Applications of Human Embryonic Stem Cells
Authors: Gepstein Lior
Published: November 2002

Embryonic stem cells are pluripotent cell lines that are derived from the blastocyst-stage early mammalian embryo. These unique cells are characterized by their capacity for prolonged undifferentiated proliferation in culture while maintaining the potential to differentiate into derivatives of all three germ layers. During in vitro differentiation, embryonic stem cells can develop into specialized somatic cells, including cardiomyocytes, and have been shown to recapitulate many processes of early embryonic development. The present review describes the derivation and unique properties of the recently described human embryonic stem cells as well as the properties of cardiomyocytes derived using this unique differentiating system. The possible applications of this system in several cardiac research areas, including developmental biology, functional genomics, pharmacological testing, cell therapy, and tissue engineering, are discussed. Because of their combined ability to proliferate indefinitely and to differentiate to mature tissue types, human embryonic stem cells can potentially provide an unlimited supply of cardiomyocytes for cell therapy procedures aiming to regenerate functional myocardium. However, many obstacles must still be overcome on the way to successful clinical utilization of these cells.
Dance Band on the
Titanic
Authors: Sussman Mark A. , McCulloch Andrew , Borg Thomas K.
Published: November 2002

Biomechanical signaling is a complex interaction of both intracellular and extracellular components. Both passive and active components are involved in the extracellular environment to signal through specific receptors to multiple signaling pathways. This review provides an overview of extracellular matrix, specific receptors, and signaling pathways for biomechanical stimulation in cardiac hypertrophy.
Deficiency in ClC-3 Chloride Channels Prevents Rat Aortic Smooth Muscle Cell Proliferation
Authors: Wang Guan-Lei , Wang Xue-Rong , Lin Mo-Jun , He Hua , Lan Xiu-Jian , Guan Yong-Yuan
Published: November 2002

Recent growing evidence suggests that chloride (Cl
−
) channels are critical to the cell cycle. In cultured rat aortic vascular smooth muscle cells (VSMCs), we have previously found that Cl
−
channel blockers inhibit endothelin-1 (ET-1)–induced cell proliferation. The present study was designed to further identify the specific Cl
−
channels responsible for VSMC proliferation. Due to the lack of a specific blocker or opener of any known Cl
−
channels, we used the antisense strategy to investigate the potential role of ClC-3, a member of the voltage-gated Cl
−
channel gene family, in cell proliferation of cultured rat aortic VSMCs. With [
3
H]-thymidine incorporation and immunoblots, we found that ET-1–induced cell proliferation was parallel to a significant increase in the endogenous expression of ClC-3 protein. Transient transfection of rat aortic VSMCs with antisense oligonucleotide specific to ClC-3 caused an inhibition in ET-1–induced expression of ClC-3 protein and cell proliferation of VSMCs in the same concentration- and time-dependent pattern, whereas sense and missense oligonucleotides resulted in no effects on ClC-3 protein expression and cell proliferation. These results strongly suggest that ClC-3 may be the Cl
−
channel involved in VSMC proliferation and thus provide compelling molecular evidence linking a specific Cl
−
channel to cell proliferation. The full text of this article is available at http://www.circresaha.org.
HuEP5C7 as a Humanized Monoclonal Anti-E/P-Selectin Neurovascular Protective Strategy in a Blinded Placebo-Controlled Trial of Nonhuman Primate Stroke
Authors: Mocco J. , Choudhri Tanvir , Huang Judy , Harfeldt Elisabeth , Efros Lyubov , Klingbeil Corine , Vexler Vladimir , Hall William , Zhang Yuan , Mack William , Popilskis Sulli , Pinsky David J. , Connolly E. Sander
Published: November 2002

Although inhibiting interaction of β
2
integrins with cognate immunoglobulin class adhesion receptor ligands is an effective neuroprotective strategy in small mammal models of stroke, the strategy has failed in human trials. A completely different antiadhesion receptor strategy was therefore rigorously tested in a model that may more closely approximate human reperfused stroke. Early leukoadhesive events in postischemic cerebral microvessels are mediated by upregulated selectin-class adhesion receptors on endothelial cells. Therefore, a blocking antibody prepared against common P- and E-selectin epitopes was humanized to suppress complement activation and tested in a reperfused hemispheric stroke model in Papio
anubis
(baboon). Histological examination of postischemic cerebral microvessels revealed a strong upregulation of E-and P-selectin expression. Placebo-blinded administration of the humanized anti-human E- and P-selectin monoclonal antibody (HuEP5C7, 20 mg/kg IV, n=9; placebo, n=9) immediately after the onset of 1 hour of temporary ischemia resulted in trends showing reduced polymorphonuclear leukocyte (PMN) infiltration into ischemic cortex, reduced infarct volumes (by 41%), improved neurological score (by 35%), and improved ability to self-care (by 39%). Importantly, there was no evidence of systemic complement activation, immune suppression, or pathological coagulopathy associated with this therapy. These data suggest that a humanized anti-E/P-selectin antibody approach is safe and may be effective as a clinical treatment for human stroke.
Phorbol Ester Induction of Angiotensin-Converting Enzyme Transcription Is Mediated by Egr-1 and AP-1 in Human Endothelial Cells via ERK1/2 Pathway
Authors: Eyries Mélanie , Agrapart Monique , Alonso Amalia , Soubrier Florent
Published: November 2002

Angiotensin-converting enzyme (ACE) is an enzyme that plays a major role in vasoactive peptide metabolism, and it has been implicated in various cardiovascular diseases. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, has been shown to increase ACE mRNA at the transcriptional level in human umbilical vein endothelial cells. We have investigated the transcriptional mechanism involved in protein kinase C induction of the ACE gene. Deletion and transfection analyses have revealed that two regions are required for PMA-inducible gene expression. The first is a G+C-rich region located in the proximal ACE promoter bearing overlapping consensus recognition sequences for stimulatory protein-1 (Sp1) and early growth response gene 1 (Egr-1). Electrophoretic mobility shift assay and supershift experiments have shown that Egr-1 is present in the specific nucleoprotein complex induced by PMA in human umbilical vein endothelial cells. The second region is located in the distal ACE promoter. DNase I footprinting analysis restricted this region to a 21-bp element containing a cAMP-responsive element/12-
O
-tetradecanoylphorbol 13-acetate–responsive element sequence. Electrophoretic mobility shift assays and supershift analyses have revealed that activating protein 1 (AP-1) is the transcription factor binding the cAMP-responsive element/12-
O
-tetradecanoylphorbol 13-acetate–responsive element located in the ACE promoter after PMA stimulation. Mutations of either Egr-1 or AP-1 binding sites partially abrogate ACE expression induced by PMA, whereas mutation of both sites totally abrogates PMA-induced ACE expression. Treatment of cells with PD98059, a mitogen-activated protein kinase kinase-1–specific inhibitor, inhibited PMA-induced ACE expression. Our results demonstrate that the two transcription factors, Egr-1 and AP-1, are involved in the PMA-induced ACE transcriptional activation in human endothelial cells via the activation of the extracellular signal–regulated kinase 1/2 signaling pathway.