bluuebunny/crossref_metadata_2025 huggingface dataset:
GAAP‐1: a transcriptional activator of p53 and IRF‐1 possesses pro‐apoptotic activity
Authors: Lallemand Christophe , Palmieri Marta , Blanchard Brigitte , Meritet Jean‐François , Tovey Michael G
Published: July 2002

The mechanisms that regulate the transcription of the tumour suppressor genes p53 and IRF‐1 are poorly understood. We have characterized a 68‐kDa transcription factor, GAAP‐1 (gatekeeper of apoptosis activating proteins), encoded by an alternative splice product of the PRDII‐BF1 gene, that recognizes a novel regulatory element within the p53 and IRF‐1 promoters. Transfection of U937 cells with GAAP‐1 activates p53 and IRF‐1 expression and leads to apoptosis, whereas over‐expression of GAAP‐1 in K562 cells that lack p53 and IRF‐1 induces cell differentiation. Alterations in the 6p24 locus containing the GAAP‐1 gene are frequent in acute myelogenous leukemia (AML), and AML‐derived cell lines display reduced GAAP‐1 mRNA levels. Together, these results suggest that GAAP‐1 acts as a gatekeeper at a critical point in the tumour suppressor gene pathway.
Comparison of two recombinant follicle-stimulating hormone preparations in in-vitro fertilization: a randomized clinical study
Authors: Tulppala Maija , Aho Milla , Tuuri Timo , Vilska Sirpa , Foudila Tuija , Hakala-Ala-Pietilä Tiina , Moilanen Jarna , Bützow Tarja , Kaukoranta Seija , Söderström-Anttila Viveca , Siegberg Rita , Suikkari Anne-Maria , Hovatta Outi
Published: July 2002

A randomized comparison of two recombinant human follicle-stimulating hormone (recFSH) preparations (Gonal-F® and Puregon®) in ovarian stimulation for in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) was carried out at the Infertility Clinic of the Family Federation of Finland. A total of 348 women (aged 22–43 years) suffering from infertility due to miscellaneous causes was recruited. Of these, 344 underwent stimulation using equal starting doses (150 IU/day: Gonal-F®n = 164, Puregon®n = 158 or 300 IU/day: Gonal-F®n = 8, Puregon®n = 14) after down-regulation with intranasal buserelin from the mid-luteal phase. Similar clinical pregnancy rates were achieved with both preparations; 33.5% per cycle and 37.4% per embryo transfer (24.5% one-embryo and 75.5% two-embryo transfers, n = 147) with Gonal-F® (150 IU/day) and 32.9% per cycle and 36.4% per embryo transfer (30.1% one-embryo and 69.9% two-embryo transfers, n = 145) with Puregon® (150 IU/day). The ongoing cumulative pregnancy rates after frozen–thawed embryo transfer were 35.4% with Gonal-F® and 37.7% with Puregon®. Six cycles were cancelled because of a low response (three in each group). Similar numbers of oocytes were obtained in both groups; 13.0 with 150 IU/day and 6.1 with 300 IU/day Gonal-F®, and 12.4 with 150 IU/day and 7.1 with 300 IU/day Puregon®. The fertilization and cleavage rates and the incidence of moderate or severe ovarian hyperstimulation syndrome (Gonal-F®, 2.0% and Puregon®, 0.7%) were also similar. Gonal-F® and Puregon® were equally and highly effective in stimulation for IVF and ICSI.
A trial comparing low-dose, short-course ciprofloxacin and standard 7 day therapy with co-trimoxazole or nitrofurantoin in the treatment of uncomplicated urinary tract infection
Authors:   the Urinary Tract Infection Group, Iravani Abdollah , Klimberg Ira , Briefer Caesar , Munera Catherine , Kowalsky Steven F. , Echols Roger M.
Published: July 2002

The study was undertaken to compare the safety and efficacy of twice-daily ciprofloxacin for 3 days with standard 7 day therapy with either co-trimoxazole or nitrofurantoin in the treatment of women with acute, uncomplicated urinary tract infections (UTI). This multicentre, prospective, randomized, double-blind trial compared oral ciprofloxacin (100 mg bd) for 3 days with co-trimoxazole (160/800 mg bd) or nitrofurantoin (100 mg bd) for 7 days. Bacteriological and clinical evaluations were performed at study entry, during therapy and 4-10 days and 4-6 weeks after the completion of therapy. The primary efficacy parameter was eradication of the causative organism 4- 10 days following treatment. Of 713 women enrolled and evaluable for safety, 521 were evaluable for efficacy (168 ciprofloxacin, 174 co-trimoxazole, 179 nitrofurantoin). Escherichia coli (83%) was the most frequently isolated pathogen in all treatment groups. Bacteriological eradication was reported in 88% of ciprofloxacin patients, 93% of co-trimoxazole patients and 86% of nitrofurantoin patients. At the 4-6 week follow-up, ciprofloxacin had statistically significantly higher eradication rates (91%) than co-trimoxazole (79%; 95% confidence limit (CL) = −20.6%, −3.9%) and nitrofurantoin (82%; 95% CL = −17.1%, −0.9%). Clinical resolution 4- 10 days after therapy and at the 4- 6 week follow-up was similar among the three treatment groups. The overall incidence of treatment-emergent adverse events was not significantly different (P= 0.093) among the three drug regimens, althousgh co-trimoxazole was associated with a greater number of adverse events than ciprofloxacin (P ≤0.05). Ciprofloxacin also caused fewer episodes of nausea than either of the other agents (P ≤0.01).
Aggregation of truncated GST--HD exon 1 fusion proteins containing normal range and expanded glutamine repeats
Authors: Hollenbach B. , Scherzinger E. , Schweiger K. , Lurz R. , Lehrach H. , Wanker E. E.
Published: July 2002

We have shown previously by electron microscopy that the purified glutathione S-transferase (GST)-Huntington'sdisease (HD) exon 1 fusion protein with 51 glutamine residues (GST-HD51) is an oligomer, and that site-specific proteolytic cleavage of this fusion protein results in the formation of insoluble more highly ordered protein aggregates with a fibrillar or ribbon-like morphology (E. Scherzinger
et al
. (1997)
Cell
90, 549-558 ). Here we report that a truncated GST-HD exon 1 fusion protein with 51 glutamine residues, which lacks the proline-rich region C-terminal to the polyglutamine (polyQ) tract (GST-HD51ΔP) self-aggregates into high-molecular-mass protein aggregates without prior proteolytic cleavage. Electron micrographs of these protein aggregates revealed thread-like fibrils with a uniform diameter of
ca
. 25 nm. In contrast, proteolytic cleavage of GST-HD51ΔP resulted in the formation of numerous clusters of high-molecular-mass fibrils with a different, ribbon-like morphology. These structures were reminiscent of prion rods and Δ-amyloid fibrils in Alzheimer'sdisease. In agreement with our previous results with full-length GST-HD exon 1, the truncated fusion proteins GST-HD20ΔP and GST-HD30ΔP did not show any tendency to form more highly ordered structures, either with or without protease treatment.
Control of mitotic transitions by the anaphase–promoting complex
Authors: Fang G. , Yu H. , Kirschner W.
Published: July 2002

Proteolysis controls key transitions at several points in the cell cycle. In mitosis, the activation of a large ubiquitin–protein ligase, the anaphase–promoting complex (APC), is required for anaphase initiation and for exit from mitosis. We show that APC is under complex control by a network of regulatory factors, CDC20, CDH1 and MAD2. CDC20 and CDH1 are activators of APC; they bind directly to APC and activate its cyclin ubiquitination activity. CDC20 activates APC at the onset of anaphase in a destruction box (DB)–dependent manner, while CDH1 activates APC from late anaphase through G1 with apparently a much relaxed specificity for the DB. Therefore, CDC20 and CDH1 control both the temporal order of activation and the substrate specificity of APC, and hence regulate different events during mitosis and G1. Counteracting the effect of CDC20, the checkpoint protein MAD2 acts as an inhibitor of APC. When the spindle–assembly checkpoint is activated, MAD2 forms a ternary complex with CDC20 and APC to prevent activation of APC, and thereby arrests cells at prometaphase. Thus, a combination of positive and negative regulators establishes a regulatory circuit of APC, ensuring an ordered progression of events through cell division.
Hierarchical organization of macaque and cat cortical sensory systems explored with a novel network processor
Authors: Hilgetag Claus–C. , O'Neill Marc A. , Young Malcolm P.
Published: July 2002

Neuroanatomists have described a large number of connections between the various structures of monkey and cat cortical sensory systems. Because of the complexity of the connection data, analysis is required to unravel what principles of organization they imply. To date, analysis of laminar origin and termination connection data to reveal hierarchical relationships between the cortical areas has been the most widely acknowledged approach. We programmed a network processor that searches for optimal hierarchical orderings of cortical areas given known hierarchical constraints and rules for their interpretation. For all cortical systems and all cost functions, the processor found a multitude of equally low–cost hierarchies. Laminar hierarchical constraints that are presently available in the anatomical literature were therefore insufficient to constrain a unique ordering for any of the sensory systems we analysed. Hierarchical orderings of the monkey visual system that have been widely reported, but which were derived by hand, were not among the optimal orderings. All the cortical systems we studied displayed a significant degree of hierarchical organization, and the anatomical constraints from the monkey visual and somatomotor systems were satisfied with very few constraint violations in the optimal hierarchies. The visual and somato–motor systems in that animal were therefore surprisingly strictly hierarchical. Most inconsistencies between the constraints and the hierarchical relationships in the optimal structures for the visual system were related to connections of area FST (fundus of superior temporal sulcus). W e found that the hierarchical solutions could be further improved by assuming that FSTconsists of two areas, which differ in the nature of their projections. Indeed, we found that perfect hierarchical arrangements of the primate visual system, without any violation of anatomical constraints, could be obtained under two reasonable conditions, namely the subdivision of FST into two distinct areas, whose connectivity we predict, and the abolition of at least one of the less reliable rule constraints. Our analyses showed that the future collection of the same type of laminar constraints, or the inclusion of new hierarchical constraints from thalamocortical connections, will not resolve the problem of multiple optimal hierarchical representations for the primate visual system. Further data, however, may help to specify the relative ordering of some more areas. This indeterminacy of the visual hierarchy is in part due to the reported absence of some connections between cortical areas. These absences are consistent with limited cross–talk between differentiated processing streams in the system. Hence, hierarchical representation of the visual system is affected by, and must take into account, other organizational features, such as processing streams.
DNA polymerase iota and related Rad30–like enzymes
Authors: McDonald John P. , Tissier Agnès , Frank Ekaterina G. , Iwai Shigenori , Hanaoka Fumio , Woodgate Roger
Published: July 2002

Until recently, the molecular mechanisms of translesion DNA synthesis (TLS), a process whereby a damaged base is used as a template for continued replication, was poorly understood. This area of scientific research has, however, been revolutionized by the finding that proteins long implicated in TLS are, in fact, DNA polymerases. Members of this so–called UmuC/DinB/Rev1/Rad30 superfamily of polymerases have been identified in prokaryotes, eukaryotes and archaea. Biochemical studies with the highly purified polymerases reveal that some, but not all, can traverse blocking lesions in template DNA. All of them share a common feature, however, in that they exhibit low fidelity when replicating undamaged DNA. Of particular interest to us is the Rad30 subfamily of polymerases found exclusively in eukaryotes. Humans possess two Rad30 paralogs, Rad30A and Rad30B. TheRAD30Agene encodes DNA polymerase η and defects in the protein lead to the xeroderma pigmentosum variant (XP–V) phenotype in humans. Very recentlyRAD30Bhas also been shown to encode a novel DNA polymerase, designated as Pol ι. Based uponin vitrostudies, it appears that Pol ι has the lowest fidelity of any eukaryotic polymerase studied to date and we speculate as to the possible cellular functions of such a remarkably error–prone DNA polymerase.
Tolerance, mixed chimerism and protection against graft-versus-host disease after total lymphoid irradiation
Authors: Field Elizabeth H. , Strober Samuel
Published: July 2002

Total lymphoid irradiation (TLI), originally developed as a non–myeloablative treatment for Hodgkin's disease, has been adapted for the induction of immune tolerance to organ allografts in rodents, dogs and non–human primates. Moreover, pretransplantation TLI has been used in prospective studies to demonstrate the feasibility of the induction of tolerance to cadaveric kidney allografts in humans. Two types of tolerance, chimeric and non–chimeric, develop after TLI treatment of hosts depending on whether donor bone marrow cells are transplanted along with the organ allograft. An advantageous feature of TLI for combined marrow and organ transplantation is the protection against graft–versus–host disease (GVHD) and facilitation of chimerism afforded by the predominance of CD4+NK1.1+–like T cells in the irradiated host lymphoid tissues. Recently, a completely post–transplantation TLI regimen has been developed resulting in stable mixed chimerism and tolerance that is enhanced by a brief course of cyclosporine. The post–transplantation protocol is suitable for clinical cadaveric kidney transplantation. This review summarizes the evolution of TLI protocols for eventual application to human clinical transplantation and discusses the mechanisms involved in the induction of mixed chimerism and protection from GVHD.
Cellular signalling and the complexity of biological timing: insights from the ultradian clock ofSchizosaccharomyces pombe
Authors: Kippert Fred
Published: July 2002

The molecular bases of circadian clocks are complex and cannot be sufficiently explained by the relatively simple feedback loops, based on transcription and translation, of current models. The existence of additional oscillators has been demonstrated experimentally, but their mechanism(s) have so far resisted elucidation and any universally conserved clock components have yet to be identified. The fission yeast,Schizosaccharomyces pombe, as a simple and well–characterized eukaryote, is a useful model organism in the investigation of many aspects of cell regulation. In fast–growing cells of the yeast an ultradian clock operates, which can serve as a model system to analyse clock complexity. This clock shares strict period homeostasis and efficient entrainment with circadian clocks but, because of its short period of 30 min, mechanisms other than a transcription/translation–based feedback loop must be working. An initial systematic screen involving over 200 deletion mutants has shown that major cellular signalling pathways (calcium/phosphoinositide, mitogen–activated protein kinase and cAMP/protein kinase A) are crucial for the normal functioning of this ultradian clock. A comparative examination of the role of cellular signalling pathways in theS.pombeultradian clock and in the circadian timekeeping of different eukaryotes may indicate common principles in biological timing processes that are universally conserved amongst eukaryotes.
A Comparative Genomic Analysis of Two Distant Diptera, the Fruit Fly, Drosophila melanogaster, and the Malaria Mosquito, Anopheles gambiae
Authors: Bolshakov Viacheslav N. , Topalis Pantelis , Blass Claudia , Kokoza Elena , della Torre Alessandra , Kafatos Fotis C. , Louis Christos
Published: July 2002

Genome evolution entails changes in the DNA sequence of genes and intergenic regions, changes in gene numbers, and also changes in gene order along the chromosomes. Genes are reshuffled by chromosomal rearrangements such as deletions/insertions, inversions, translocations, and transpositions. Here we report a comparative study of genome organization in the main African malaria vector,Anopheles gambiae, relative to the recently determined sequence of the Drosophila melanogaster genome. The ancestral lines of these two dipteran insects are thought to have separated ∼250 Myr, a long period that makes this genome comparison especially interesting. Sequence comparisons have identified 113 pairs of putative orthologs of the two species. Chromosomal mapping of orthologous genes reveals that each polytene chromosome arm has a homolog in the other species. Between 41% and 73% of the known orthologous genes remain linked in the respective homologous chromosomal arms, with the remainder translocated to various nonhomologous arms. Within homologous arms, gene order is extensively reshuffled, but a limited degree of conserved local synteny (microsynteny) can be recognized.
BAC Library of T. pallidum DNA in E. coli
Authors: Šmajs David , McKevitt Matthew , Wang Ling , Howell Jerrilyn K. , Norris Steven J. , Palzkill Timothy , Weinstock George M.
Published: July 2002

Treponema pallidum subspecies pallidum (Nichols) chromosomal DNA was used to construct a large insert bacterial artificial chromosome (BAC) library in Escherichia coli DH10B using the pBeloBAC11 cloning vector; 678 individual insert termini of 339 BAC clones (13.9 x coverage) were sequenced and the cloned chromosomal region in each clone was determined by comparison to the genomic sequence. A single 15.6-kb region of the T. pallidumchromosome was missing in the BAC library, between bp 248727 and 264323. In addition to the 12 open reading frames (ORFs) coded by this region, one additional ORF (TP0596) was not cloned as an intact gene. Altogether, 13 predicted T. pallidum ORFs (1.25% of the total) were incomplete or missing in the library. Three of 338 clones mapped by restriction enzyme digestion had detectable deletions and one clone had a detectable insertion within the insert. Of mapped clones, 19 were selected to represent the minimal set of E. coli BAC clones covering 1026 of the total 1040 (98.7%) predicted T. pallidum ORFs. Using this minimal set of clones, at least 12T. pallidum proteins were shown to react with pooled sera from rabbits immunized with T. pallidum, indicating that at least some T. pallidum genes are transcribed and expressed inE. coli.
A novel approach for assesing macromolecular complexes combining soft‐docking calculations with NMR data
Authors: Morelli Xavier J. , Palma P. Nuno , Guerlesquin Françoise , Rigby Alan C.
Published: July 2002

We present a novel and efficient approach for assessing protein–protein complex formation, which combines ab initio docking calculations performed with the protein docking algorithm BiGGER and chemical shift perturbation data collected with heteronuclear single quantum coherence (HSQC) or TROSY nuclear magnetic resonance (NMR) spectroscopy. This method, termed “restrained soft‐docking,” is validated for several known protein complexes. These data demonstrate that restrained soft‐docking extends the size limitations of NMR spectroscopy and provides an alternative method for investigating macromolecular protein complexes that requires less experimental time, effort, and resources. The potential utility of this novel NMR and simulated docking approach in current structural genomic initiatives is discussed.
Hydroxynonenal inactivates cathepsin B by forming Michael adducts with active site residues
Authors: Crabb John W. , O'Neil June , Miyagi Masaru , West Karen , Hoff Henry F.
Published: July 2002

Oxidation of plasma low‐density lipoprotein (oxLDL) generates the lipid peroxidation product 4‐hydroxy‐2 nonenal (HNE) and also reduces proteolytic degradation of oxLDL and other proteins internalized by mouse peritoneal macrophages in culture. This leads to accumulation of undegraded material in lysosomes and formation of ceroid, a component of foam cells in atherosclerotic lesions. To explore the possibility that HNE contributes directly to the inactivation of proteases, structure‐function studies of the lysosomal protease cathepsin B have been pursued. We found that treatment of mouse macrophages with HNE reduces degradation of internalized maleyl bovine serine albumin and cathepsin B activity. Purified bovine cathepsin B treated briefly with 15 μM HNE lost ∼76% of its protease activity and also developed immunoreactivity with antibodies to HNE adducts in Western blot analysis. After stabilization of the potential Michael adducts by sodium borohydride reduction, modified amino acids were localized within the bovine cathepsin B protein structure by mass spectrometric analysis of tryptic peptides. Michael adducts were identified by tandem mass spectrometry at cathepsin B active site residues Cys 29 (mature A chain) and His 150 (mature B chain). Thus, covalent interaction between HNE and critical active site residues inactivates cathepsin B. These results support the hypothesis that the accumulation of undegraded macromolecules in lysosomes after oxidative damage are caused in part by direct protease inactivation by adduct formation with lipid peroxidation products such as HNE.
High stability of a ferredoxin from the hyperthermophilic archaeon A. ambivalens: Involvement of electrostatic interactions and cofactors
Authors: Moczygemba Charmaine , Guidry Jesse , Jones Kathryn L. , Gomes Cláudio M. , Teixeira Miguel , Wittung‐Stafshede Pernilla
Published: July 2002

The ferredoxin from the thermophilic archaeon Acidianus ambivalens is a small monomeric seven‐iron protein with a thermal midpoint (Tm) of 122°C (pH 7). To gain insight into the basis of its thermostability, we have characterized unfolding reactions induced chemically and thermally at various pHs. Thermal unfolding of this ferredoxin, in the presence of various guanidine hydrochloride (GuHCl) concentrations, yields a linear correlation between unfolding enthalpies (ΔH[Tm]) and Tm from which an upper limit for the heat capacity of unfolding (ΔCP) was determined to be 3.15 ± 0.1 kJ/(mole • K). Only by the use of the stronger denaturant guanidine thiocyanate (GuSCN) is unfolding of A. ambivalens ferredoxin at pH 7 (20°C) observed ([GuSCN]1/2 = 3.1 M; ΔGU[H2O] = 79 ± 8 kJ/mole). The protein is, however, less stable at low pH: At pH 2.5, Tm is 64 ± 1°C, and GuHCl‐induced unfolding shows a midpoint at 2.3 M (ΔGU[H2O] = 20 ± 1 kJ/mole). These results support that electrostatic interactions contribute significantly to the stability. Analysis of the three‐dimensional molecular model of the protein shows that there are several possible ion pairs on the surface. In addition, ferredoxin incorporates two iron–sulfur clusters and a zinc ion that all coordinate deprotonated side chains. The zinc remains bound in the unfolded state whereas the iron–sulfur clusters transiently form linear three‐iron species (in pH range 2.5 to 10), which are associated with the unfolded polypeptide, before their complete degradation.
The potential role of positron emission mammography for detection of breast cancer. A phantom study
Authors: Raylman Raymond R. , Majewski Stan , Wojcik Randy , Weisenberger Andrew G. , Kross Brian , Popov Vladimir , Bishop Harry A.
Published: July 2002

Positron emission mammography (PEM) is a new, specialized imaging modality utilizing PET radiopharmaceuticals to detect breast cancer. The capabilities and limitations of PEM in detecting breast tumors were investigated with a series of phantom experiments. The PEM imager was mounted on a standard Lorad biopsy table (separated by 18 cm). In the initial phase of the investigation, basic scanner parameters (resolution, sensitivity, and scatter fraction) were measured. The effects of a number of breast imaging parameters (length of acquisition, breast thickness, and breast density) on detection of breast lesions were then explored utilizing special phantoms. Moderately compressed breasts were simulated with a block of gelatin containing amounts of FDG consistent with 370 MBq injections. Lesions were simulated with four hollow spheres (inner diameters=5 mm, 8 mm, 12 mm, and 15 mm) filled with amounts of FDG representative of uptake in malignant breast tumors (target‐to‐background concentration ratio=8.5 : 1). Resolution at the center of the imager was 3.9 mm, sensitivity was 0.059 kcps/kBq/ml and the Compton scatter fraction was ∼12%. Objects as small as 8 mm in diameter could be detected after 30 s of data acquisition; 5 mm spheres were detectable after 300 s. Object detection capabilities were reduced with increasing breast thickness. In thin compressed breasts (2 cm) even the smallest sphere (5 mm in diameter) could be detected; increasing breast thickness increased the minimum detectable sphere diameter to 8 mm. Increased background activity caused by FDG uptake in metabolically active normal tissue more prevalent in radiodense breasts compared to “fatty” breasts was simulated and shown to reduce the minimum detectable lesion size to 12 mm for the densest breasts. These results demonstrate the potential of PEM for the detection of breast lesions. The addition of the system to a standard biopsy apparatus indicates its potential for use to guide some core biopsies of breast cancers.
Electron fluence correction factors for various materials in clinical electron beams
Authors: Olivares M. , DeBlois F. , Podgorsak E. B. , Seuntjens J. P.
Published: July 2002

Relative to solid water, electron fluence correction factors at the depth of dose maximum in bone, lung, aluminum, and copper for nominal electron beam energies of 9 MeV and 15 MeV of the Clinac 18 accelerator have been determined experimentally and by Monte Carlo calculation. Thermoluminescent dosimeters were used to measure depth doses in these materials. The measured relative dose at in the various materials versus that of solid water, when irradiated with the same number of monitor units, has been used to calculate the ratio of electron fluence for the various materials to that of solid water. The beams of the Clinac 18 were fully characterized using the EGS4/BEAM system. EGSnrc with the relativistic spin option turned on was used to optimize the primary electron energy at the exit window, and to calculate depth doses in the five phantom materials using the optimized phase‐space data. Normalizing all depth doses to the dose maximum in solid water stopping power ratio corrected, measured depth doses and calculated depth doses differ by less than ±1% at the depth of dose maximum and by less than 4% elsewhere. Monte Carlo calculated ratios of doses in each material to dose in LiF were used to convert the TLD measurements at the dose maximum into dose at the center of the TLD in the phantom material. Fluence perturbation correction factors for a LiF TLD at the depth of dose maximum deduced from these calculations amount to less than 1% for 0.15 mm thick TLDs in low Z materials and are between 1% and 3% for TLDs in Al and Cu phantoms. Electron fluence ratios of the studied materials relative to solid water vary between and for materials varying in density from 0.27 g/cm3 (lung) to 8.96 g/cm3 (Cu). The difference in electron fluence ratios derived from measurements and calculations ranges from −1.6% to +0.2% at 9 MeV and from −1.9% to +0.2% at 15 MeV and is not significant at the 1σ level. Excluding the data for Cu, electron fluence correction factors for open electron beams are approximately proportional to the electron density of the phantom material and only weakly dependent on electron beam energy.
Relationship between phantom failure rates and radiation dose in mammography accreditation
Authors: Haus Arthur G. , Yaffe Martin J. , Feig Stephen A. , Hendrick R. Edward , Butler Priscilla A. , Wilcox Pamela A. , Bansal Swati
Published: July 2002

The American College of Radiology Mammography Accreditation Program (ACR MAP) reviews both clinical mammograms and a phantom image to assess clinical and technical quality from each mammography unit. The phantom contains details representing fibers (speculations), speck groups (microcalcifications), and masses. The depiction of these structures by the mammographic system is scored by medical physicists. The phantom image is taken using the facility's exposure technique for a 4.2‐cm thick breast of average composition. The mean glandular dose (MGD) is determined from a set of thermoluminescent dosimeters placed on top of the chest wall edge of the phantom. Phantom scores and MGD data collected from 1993 to 1999 based on 31 535 unit evaluations are presented in this paper. The relationship between the failure rate for phantom image quality and MGD has been analyzed. While over all doses the phantom failure rate was 11%, for doses of 0.26 to 0.50 mGy the failure rate was 43%. The phantom failure rate fell continuously to about 6% for MGDs in the range of 1.51–2.0 mGy. With further increases in dose, failure rates began to rise. Factors that may account for these results are presented and discussed.
Benchmarking of the Dose Planning Method (DPM) Monte Carlo code using electron beams from a racetrack microtron
Authors: Chetty Indrin J. , Moran Jean M. , McShan Daniel L. , Fraass Benedick A. , Wilderman Scott J. , Bielajew Alex F.
Published: July 2002

A comprehensive set of measurements and calculations has been conducted to investigate the accuracy of the Dose Planning Method (DPM) Monte Carlo code for dose calculations from 10 and 50 MeV scanned electron beams produced from a racetrack microtron. Central axis depth dose measurements and a series of profile scans at various depths were acquired in a water phantom using a Scanditronix type RK ion chamber. Source spatial distributions for the Monte Carlo calculations were reconstructed from in‐air ion chamber measurements carried out across the two‐dimensional beam profile at 100 cm downstream from the source. The in‐air spatial distributions were found to have full width at half maximum of 4.7 and 1.3 cm, at 100 cm from the source, for the 10 and 50 MeV beams, respectively. Energy spectra for the 10 and 50 MeV beams were determined by simulating the components of the microtron treatment head using the code MCNP4B. DPM calculations are on average within ±2% agreement with measurement for all depth dose and profile comparisons conducted in this study. The accuracy of the DPM code illustrated in this work suggests that DPM may be used as a valuable tool for electron beam dose calculations.
A continuous penalty function method for inverse treatment planning
Authors: Hristov Dimitre H. , Fallone B. Gino
Published: July 2002

Conventional inverse treatment planning attempts to calculate dose distributions that may not be feasible given the specified dose levels to various anatomical structures. A technique for inverse treatment planning has been developed that uses only target dose levels which are easily selectable to be feasible. A nonlinear constrained minimization problem is formulated to reflect the goal of sparing critical organs as much as possible while delivering a certain target dose within specified uniformity. The objective function is the squared dose delivered to critical organs. The constraints require the delivery of certain target dose within specified uniformity and non‐negative pencil beam weights. A continuous penalty function method is introduced as a method for solving the large‐scale constrained minimization problem. The performance of the continuous penalty function method is optimized by numerical investigation of few numerical integration schemes and a pair of weighting functions which influence the utility of the method. Clinical examples are presented that illustrate several features of the technique. The properties of the continuous penalty function method suggest that it may be a viable alternative to conventional inverse treatment planning.
Variation method for inverse treatment planning
Authors: Liu Yi , Yin Fang‐Fang , Gao Qinghuai
Published: July 2002

A new inverse planning method based on the theory of variation is developed for the computation of beam intensities that produce highly conformal dose distributions to the target volume that have an arbitrary complex geometry. It is shown that the objective function defined for the optimization of external beam intensities has a unique minimum. A corresponding algorithm is then designed to generate a sequence of intensity functions that converge to the minimum. The algorithm is applied to a test geometry where the target volume has concavity and there are adjacent critical organs. The cumulative dose–area histogram, the two‐dimensional version of the cumulative dose–volume histogram, is used to evaluate the outcomes of this new inverse planning method. The results show that this method creates a group of intensity‐modulated external beams that produce a dose distribution consistent with the given dose prescription.
Localization of a pontine vocalization-controlling area
Authors: Jürgens Uwe
Published: July 2002

To find out whether there exist additional regions in the pontine brainstem, apart from the phonatory motoneuron pools involved in vocal motor control, the effects of a localized blockade of excitatory neurotransmission in the pons were studied on squirrel monkey vocalization. Vocalization was elicited by electrical stimulation of the periaqueductal gray of the midbrain. Blockade was carried out by stereotaxic injections of kynurenic acid, a nonspecific glutamate antagonist. It was found that injections made into the ventrolateral pons around the ventral nucleus of the lateral lemniscus and superior olive could block periaqueductally elicited vocalization. Injections were only effective ipsilaterally, not contralaterally to the stimulation site. The blockade was limited to one particular class of calls, all of which had in common a characteristic stereotyped frequency modulation over several kHz. It is concluded that critical processing steps of vocal motor control take place in the periolivary region.
Surface diffusion coefficients for room acoustics: Free-field measures
Authors: Hargreaves Tristan J. , Cox Trevor J. , Lam Y. W. , D’Antonio Peter
Published: July 2002

A surface diffusion coefficient is needed in room acoustics to enable the quality of diffusing surfaces to be evaluated. It may also facilitate more accurate geometric room acoustic models. This paper concentrates on diffusion coefficients derived from free-field polar responses. An extensive set of two- and three-dimensional measurements and predictions was used to test the worth of different diffusion coefficient definitions. The merits and problems associated with these types of coefficients are discussed, and past parameters reviewed. Two new coefficients are described. The new measure based on the autocorrelation function is forwarded as the best free-field coefficient. The strengths and weaknesses of the coefficient are defined.
Acoustically coupled gas bubbles in fluids: Time-domain phenomena
Authors: Feuillade Christopher
Published: July 2002

In previous work [C. Feuillade, J. Acoust. Soc. Am. 98, 1178–1190 (1995)] a coupled oscillator formalism was introduced for describing collective resonances, scattering, and superresonances, of multiple gas bubbles in a fluid. Subsequently, time-domain investigations of the impulse response of coupled systems have disclosed the exact conditions which determine whether the ensemble scattering behavior should be described using: either (a), a multiple scattering; or (b), a self-consistent methodology. The determining factor is the Q of the individual scatterers, and their typical spatial separations in the medium. For highly damped or sparse systems, e.g., scattering from loose schools of swimbladder fish, or from a gassy seabed containing entrained bubbles, the multiple scatter counting approach should be applicable. For more strongly coupled systems, e.g., a dense cloud of resonating bubbles in the water column, energy exchange may be due primarily to radiative cycling rather than scattering, in which case a self-consistent approach is indicated. The result has implications for both volume and bottom scattering applications.
Sonic boom in the shadow zone: A geometrical theory of diffraction
Authors: Coulouvrat François
Published: July 2002

Geometrical acoustics predicts the amplitude of sonic booms only within the carpet. Inside the geometrical shadow zone, a nonlinear, geometrical theory of diffraction in the time domain is proposed. An estimation of magnitude orders shows that nonlinear effects are expected to be small for usual sonic booms. In the linear case, the matching to geometrical acoustics yields an analytical expression for the pressure near the cutoff. In the shadow zone, it can be written as a series of creeping waves. Numerical simulations show that the amplitude decay of the signal compares favorably with Concorde measurements, while the magnitude order of the rise time is correct. The ground impedance is shown to influence the rise time and peak amplitude of the signal mostly close to the cutoff. In the case of a weakly refractive atmosphere (low temperature gradient or downwind propagation), the transition zone about the cutoff is large, the transition is smooth, and the influence of ground absorption is increased.
Optimum sensor–actuator distance for decentralized acoustic control
Authors: Berkhoff Arthur P.
Published: July 2002

This paper presents simulation results of a decentralized system for the active minimization of noise transmitted through a plate. The systems are analyzed for harmonic disturbances with respect to stability, convergence, reduction of transmitted sound power, the distance between actuators and sensors, and sensitivity for reverberating environments. Assuming a particular stabilization scheme, it is shown that an optimum exists for the actuator–sensor distance in a broadband sense.
Challenging the notion of innate phonetic boundaries
Authors: Nittrouer Susan
Published: July 2002

Numerous studies of infants’ speech perception abilities have demonstrated that these young listeners have access to acoustic detail in the speech signal. Because these studies have used stimuli that could be described in terms of adult-defined phonetic categories, authors have concluded that infants innately recognize stimuli as members of these categories, as adults do. In fact, the predominant, current view of speech perception holds that infants are born with sensitivities for the universal set of phonetic boundaries, and that those boundaries supported by the ambient language are maintained, while those not supported by the ambient language dissolve. In this study, discrimination abilities of 46 infants and 75 3-year-olds were measured for several phonetic contrasts occurring in their native language, using natural and synthetic speech. The proportion of children who were able to discriminate any given contrast varied across contrasts, and no one contrast was discriminated by anything close to all of the children. While these results did not differ from those reported by others, the interpretation here is that we should reconsider the notion of innate phonetic categories and/or boundaries. Moreover, success rates did not differ for natural and synthetic speech, and so a minor conclusion was that children are not adversely affected by the use of synthetic stimuli in speech experiments.
Sound fields in a rectangular enclosure under active sound transmission control
Authors: Lau S. K. , Tang S. K.
Published: July 2002

The present study evaluates the effectiveness of active sound transmission control inside an enclosure using a purely acoustic source under the potential energy, squared pressure, and energy density control algorithms. Full coupling between a flexible boundary wall and the interior acoustic cavity is considered. Formulas based on the impedance-mobility approach are developed for the active control of sound transmission with the energy density control algorithm. The resultant total acoustic potential energy attenuation and sound fields under the three control algorithms are compared. Global amplification of the sound level with localized quiet zones under the squared pressure control is observed. This adverse effect can be removed by using the energy density control. It is also shown that the energy density control provides a more uniform control of sound field. Better performance of global and local control of sound field using the squared pressure and energy density controls can be achieved by locating the error sensors at the peak quiet zones and the areas of peak energy density attenuation, respectively, obtained under potential energy control.
The two-component representation of time-harmonic elastic body waves in the high- and intermediate-frequency regimes
Authors: Fradkin Larissa Ju. , Kiselev Aleksei P.
Published: July 2002

Propagation and diffraction of time-harmonic elastic body waves through homogeneous and isotropic materials is revisited. The two-component representation of body waves is given which is applicable in the high- and intermediate-frequency regimes when the family of rays is (i) regular or (ii) possesses an irregularity due to the presence of a wedge, an acoustic point source located on the boundary, simple caustic, or focal line. Both physical and mathematical description of the phenomena under consideration is offered. The resulting expressions are asymptotic in character and easy to compute. They should prove useful in producing algorithms for describing acoustic fields in homogeneous and isotropic materials with isolated defects and in providing benchmark cases for testing numerical codes designed to solve elastic wave equations in more complicated situations.
Acoustic characterization of an adult bubble injected into a fully developed turbulent flow field
Authors: Kolaini Ali R. , Goumilevski Alexei G.
Published: July 2002

The acoustical characteristics of bubbles injected into a fully developed turbulent flow field are studied. By injecting an “adult” bubble into a flow, generated by a submerged axisymmetric horizontal water jet, the acoustic reexcitation of the bubble with and without breakup may occur in the shear-induced flow region. Bubbles of various sizes were introduced into jets of various speeds by means of interchangeable hypodermic needles. Results of the role of the turbulent flow characteristics in determining the acoustic bubble response are discussed. The characterizations of both the acoustical and the dynamics of the bubbles encountering a turbulent flow field depend upon the estimated integral and microlength scales, the corresponding Reynolds numbers, and the critical Weber numbers for both bubble distortion and breakup. A critical Weber number was estimated to be 0.52 for an “adult” bubble acoustic reexcitation without breakup and 1.10 for bubble breakup. A simple model is given to account for the bubble acoustic radiation. The Rayleigh–Plesset equation was altered by incorporating the turbulent pressure fluctuation of the flow as a driving force of the bubble. The turbulent energy spectrum obtained experimentally was used to predict the monopole acoustic emission by the bubble. Some conclusions are given about the nature of the turbulent flow field and conditions under which the bubble acoustic reexcitation may occur.
Sound propagation in an irregular two-dimensional waveguide
Authors: Spivack Mark
Published: July 2002

A method is presented for the numerical calculation of a scalar wave propagating along a two-dimensional rough-sided or irregular waveguide. In this situation the wave becomes multiply scattered, with simultaneous interaction at the two boundaries. The field can be expressed in terms of a pair of coupled integral equations; these are derived and solved in an approach based on the parabolic integral equation method, which assumes that all energy is carried in a forward direction. An extended formulation encompassing backscatter is also derived, and a method given for its treatment. This paper serves in part to explain the computational results presented in B. J. Uscinski, “High-frequency propagation in shallow water,” J. Acoust. Soc. Am. 98, 2702–2707 (1995).
The relation between gap detection, loudness, and loudness growth in noise-masked normal-hearing listeners
Authors: Hall Joseph W. , Grose John H.
Published: July 2002

Gap detection was measured for 50 and 1000-Hz-wide noise markers arithmetically centered on 1000 Hz. The markers were presented in a lowpass background noise having a high-frequency cutoff of 2000 Hz. The pressure spectrum level of the background noise was either 0 or 40 dB/Hz. Gap detection was determined at sensation levels (SLs) of 10, 15, 20, and 30 dB in the 0-dB/Hz background, and at SLs of 10, 15, and 20 dB in the 40-dB/Hz background. Because loudness increased more steeply in the higher level noise background, the markers in the 40-dB/Hz background were at higher loudness (and at a steeper portion of the loudness growth function) than markers in the 0-dB/Hz background, for markers matched in terms of SL. The main goal of the experiment was to determine whether gap detection would be relatively poor at steep portions of the loudness growth function due to the gap being confused with ongoing random dips. Such confusion might be particularly great when the noise bandwidth was narrow (and therefore characterized by prominent fluctuation) and the growth of loudness was steep. Gap detection was poorer for the 50-Hz-wide marker than for the 1000-Hz-wide marker. For a given marker bandwidth at a given SL, gap detection was similar whether the marker was presented in the 0-dB/Hz noise or the 40-dB/Hz noise. Supplementary conditions indicated that (1) gap detection results for 50-Hz-wide markers presented at equal SL’s were also similar between a 0-dB/Hz noise background and a 55-dB/Hz noise background, and that (2) gap detection for 50- and 1000-Hz-wide markers was poorer in a 40-dB/Hz background than in a 0-dB/Hz background when markers were matched for loudness. The results generally indicated similar gap detection thresholds for markers presented at similar SLs across a relatively wide range of background noise levels. Gap detection was related more closely to the marker-to-noise ratio than to the loudness relation between markers or the steepness of loudness growth.
Acousto-elastic multiple scattering: A comparison of ultrasonic experiments with multiple multipole expansions
Authors: Imhof Matthias G. , Toksöz M. Nafi
Published: July 2002

Solid rods are submerged in a water tank and illuminated by an ultrasonic source transducer. Along the water surface, transducers are used to measure the propagating wave fields. Even for only three rods, the scattered wave field is very complex. Although the major events can be readily interpreted as direct reflections, the remaining wave field consists of complicated interactions of the wave fields with the scatterers and the water surface. To aid the interpretation, the experiment is modeled numerically using the multiple multipoles method which decomposes the wave fields by their respective origins. Hence, particular events can be correlated with particular scatterers as well as with particular paths of propagation. The numerical method has already been used as a versatile tool to model acoustic or elastic multiple-scattering problems where homogeneous scatterers were embedded in a homogeneous full space. In the present paper, the scheme is expanded to multiple scattering between solids submerged in a fluid. For each scatterer, the waves induced in the fluid are expressed by sets of multipole solutions with different origins. Thus by construction, the scattered wave fields are decomposed by scatterer. The numerical solutions match the ultrasonic experiments very well. Furthermore, the different events can be identified as reflections, internal multiples, or diffractions through the solid rods.