bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Allogeneic Tumor Cell Vaccination and Systemic Interleukin 12 Prevents Mammary Carcinogenesis in HER-2/neu Transgenic Mice
Authors: Nanni Patrizia , Nicoletti Giordano , De Giovanni Carla , Landuzzi Lorena , Di Carlo Emma , Cavallo Federica , Pupa Serenella M. , Rossi Ilaria , Colombo Mario P. , Ricci Cinzia , Astolfi Annalisa , Musiani Piero , Forni Guido , Lollini Pier-Luigi
Published: July 2002

Transgenic Balb/c mice expressing the transforming rat HER-2/neu oncogene develop early and multifocal mammary carcinomas. Within the first 5 months of life the tissue-specific expression of HER-2/neu causes a progression in all their 10 mammary glands from atypical hyperplasia to invasive carcinoma. It was previously observed that chronic administration of interleukin (IL)-12 increased tumor latency, but every mouse eventually succumbed to multiple carcinomas. A significant improvement in tumor prevention was sought by administering allogeneic mammary carcinoma cells expressing HER-2/neu combined with systemic IL-12. This treatment reduced tumor incidence by 90% and more than doubled mouse lifetime. For the maximum prevention p185neu antigen must be expressed by allogeneic cells. IL-12 treatment strongly increased the cell vaccine efficacy. The mammary glands of mice receiving the combined treatment displayed a markedly reduced epithelial cell proliferation, angiogenesis, and HER-2/neu expression, while the few hyperplastic foci were heavily infiltrated by granulocytes, macrophages, and CD8+ lymphocytes. Specific anti–HER-2/neu antibodies were produced and a nonpolarized activation of CD4+ and CD8+ cells secreting IL-4 and interferon (IFN)-γ were evident. A central role for IFN-γ in the preventive effect was proven by the lack of efficacy of vaccination in IFN-γ gene knockout HER-2/neu transgenic Balb/c mice. A possible requirement for IFN-γ is related to its effect on antibody production, in particular on IgG2a and IgG2b subclasses, that were not induced in IFN-γ knockout HER-2/neu mice. In conclusion, our data show that an allogeneic HER-2/neu–expressing cell vaccine combined with IL-12 systemic treatment can prevent the onset of genetically determined tumors.
Blockade of a Retinal cGMP-gated Channel by Polyamines
Authors: Lu Zhe , Ding Long
Published: July 2002

The cyclic nucleotide–gated (CNG) channel in retinal rods converts the light-regulated intracellular cGMP concentration to various levels of membrane potential. Blockade of the channel by cations such as Ca2+ and Mg2+ lowers its effective conductance. Consequently, the membrane potential has very low noise, which enables rods to detect light with extremely high sensitivity. Here, we report that three polyamines (putrescine, spermidine, and spermine), which exist in both the intracellular and extracellular media, also effectively block the CNG channel from both sides of the membrane. Among them, spermine has the greatest potency. Extracellular spermine blocks the channel as a permeant blocker, whereas intracellular spermine appears to block the channel in two conformations—one permeant, and the other non- (or much less) permeant. The membrane potential in rods is typically depolarized to approximately −40 mV in the dark. At this voltage, K1/2 of the CNG channel for extracellular spermine is 3 μM, which is 100–1,000-fold higher affinity than that of the NMDA receptor-channel for extracellular spermine. Blockade of the CNG channel by polyamines may play an important role in suppressing noise in the signal transduction system in rods.
Augmentation of Recovery from Inactivation by Site-3 Na Channel Toxins
Authors: Richard Benzinger G. , Tonkovich Gayle S. , Hanck Dorothy A.
Published: July 2002

Site-3 toxins isolated from several species of scorpion and sea anemone bind to voltage-gated Na channels and prolong the time course of INa by interfering with inactivation with little or no effect on activation, effects that have similarities to those produced by genetic diseases in skeletal muscle (myotonias and periodic paralysis) and heart (long QT syndrome). Some published reports have also reported the presence of a noninactivating persistent current in site-3 toxin-treated cells. We have used the high affinity site-3 toxin Anthopleurin B to study the kinetics of this current and to evaluate kinetic differences between cardiac (in RT4-B8 cells) and neuronal (in N1E-115 cells) Na channels. By reverse transcription–PCR from N1E-115 cell RNA multiple Na channel transcripts were detected; most often isolated were sequences homologous to rBrII, although at low frequency sequences homologous to rPN1 and rBrIII were also detected. Toxin treatment induced a voltage-dependent plateau current in both isoforms for which the relative amplitude (plateau current/peak current) approached a constant value with depolarization, although the magnitude was much greater for neuronal (17%) than cardiac (5%) INa. Cell-attached patch recordings revealed distinct quantitative differences in open times and burst durations between isoforms, but for both isoforms the plateau current comprised discrete bursts separated by quiescent periods, consistent with toxin induction of an increase in the rate of recovery from inactivation rather than a modal failure of inactivation. In accord with this hypothesis, toxin increased the rate of whole-cell recovery at all tested voltages. Moreover, experimental data support a model whereby recovery at negative voltages is augmented through closed states rather than through the open state. We conclude that site-3 toxins produce qualitatively similar effects in cardiac and neuronal channels and discuss implications for channel kinetics.
Mechanism of Cgmp-Gated Channel Block by Intracellular Polyamines
Authors: Guo Donglin , Lu Zhe
Published: July 2002

Polyamines block the retinal cyclic nucleotide-gated channel from both the intracellular and extracellular sides. The voltage-dependent mechanism by which intracellular polyamines inhibit the channel current is complex: as membrane voltage is increased in the presence of polyamines, current inhibition is not monotonic, but exhibits a pronounced damped undulation. To understand the blocking mechanism of intracellular polyamines, we systematically studied the endogenous polyamines as well as a series of derivatives. The complex channel-blocking behavior of polyamines can be accounted for by a minimal model whereby a given polyamine species (e.g., spermine) causes multiple blocked channel states. Each blocked state represents a channel occupied by a polyamine molecule with characteristic affinity and probability of traversing the pore, and exhibits a characteristic dependence on membrane voltage and cGMP concentration.
Regulation of Cloned Atp–Sensitive K Channels by Phosphorylation, Mgadp, and Phosphatidylinositol Bisphosphate (Pip2)
Authors: Ribalet Bernard , John Scott A. , Weiss James N.
Published: July 2002

Kir6.2 channels linked to the green fluorescent protein (GFP) (Kir6.2-GFP) have been expressed alone or with the sulfonylurea receptor SUR1 in HEK293 cells to study the regulation of KATP channels by adenine nucleotides, phosphatidylinositol bisphosphate (PIP2), and phosphorylation. Upon excision of inside-out patches into a Ca2+- and MgATP-free solution, the activity of Kir6.2-GFP+SUR1 channels spontaneously ran down, first quickly within a minute, and then more slowly over tens of minutes. In contrast, under the same conditions, the activity of Kir6.2-GFP alone exhibited only slow rundown. Thus, fast rundown is specific to Kir6.2-GFP+SUR1 and involves SUR1, while slow rundown is a property of both Kir6.2-GFP and Kir6.2-GFP+SUR1 channels and is due, at least in part, to Kir6.2 alone. Kir6.2-GFP+SUR1 fast phase of rundown was of variable amplitude and led to increased ATP sensitivity. Excising patches into a solution containing MgADP prevented this phenomenon, suggesting that fast rundown involves loss of MgADP-dependent stimulation conferred by SUR1. With both Kir6.2-GFP and Kir6.2-GFP+SUR1, the slow phase of rundown led to further increase in ATP sensitivity. Ca2+ accelerated this process, suggesting a role for PIP2 hydrolysis mediated by a Ca2+-dependent phospholipase C. PIP2 could reactivate channel activity after a brief exposure to Ca2+, but not after prolonged exposure. However, in both cases, PIP2 reversed the increase in ATP sensitivity, indicating that PIP2 lowers the ATP sensitivity by increasing Po as well as by decreasing the channel affinity for ATP. With Kir6.2-GFP+SUR1, slow rundown also caused loss of MgADP stimulation and sulfonylurea inhibition, suggesting functional uncoupling of SUR1 from Kir6.2-GFP. Ca2+ facilitated the loss of sensitivity to MgADP, and thus uncoupling of the two subunits. The nonselective protein kinase inhibitor H-7 and the selective PKC inhibitor peptide 19-36 evoked, within 5–15 min, increased ATP sensitivity and loss of reactivation by PIP2 and MgADP. Phosphorylation of Kir6.2 may thus be required for the channel to remain PIP2 responsive, while phosphorylation of Kir6.2 and/or SUR1 is required for functional coupling. In summary, short-term regulation of Kir6.2+SUR1 channels involves MgADP, while long-term regulation requires PIP2 and phosphorylation.
Conformally invariant Monge-Ampère equations: Global solutions
Authors: Viaclovsky Jeff
Published: July 2002

In this paper we will examine a class of fully nonlinear partial differential equations which are invariant under the conformal group

S
O
(
n
+
1
,
1
)

SO(n+1,1)

. These equations are elliptic and variational. Using this structure and the conformal invariance, we will prove a global uniqueness theorem for solutions in

R

n

\mathbf {R}^n

with a quadratic growth condition at infinity.
Class number 5, 6 and 7
Authors: Wagner Christian
Published: July 2002

We outline the determination of all imaginary quadratic fields with class number 5, 6 or 7.
Zariski geometries
Authors: Hrushovski Ehud , Zilber Boris
Published: July 2002

A characterization is obtained of the Zariski topology over an algebraically closed field.
Erv14p Directs a Transmembrane Secretory Protein into COPII-coated Transport Vesicles
Authors: Powers Jacqueline , Barlowe Charles
Published: July 2002

Erv14p is a conserved integral membrane protein that traffics in COPII-coated vesicles and localizes to the early secretory pathway in yeast. Deletion of ERV14 causes a defect in polarized growth because Axl2p, a transmembrane secretory protein, accumulates in the endoplasmic reticulum and is not delivered to its site of function on the cell surface. Herein, we show that Erv14p is required for selection of Axl2p into COPII vesicles and for efficient formation of these vesicles. Erv14p binds to subunits of the COPII coat and binding depends on conserved residues in a cytoplasmically exposed loop domain of Erv14p. When mutations are introduced into this loop, an Erv14p-Axl2p complex accumulates in the endoplasmic reticulum, suggesting that Erv14p links Axl2p to the COPII coat. Based on these results and further genetic experiments, we propose Erv14p coordinates COPII vesicle formation with incorporation of specific secretory cargo.
A cluster validity framework for genome expression data
Authors: Azuaje F.
Published: July 2002

Summary: This paper presents a method for the assessment of expression cluster validity.

Availability: Executable programs are available on request from the author.

Contact: Francisco.Azuaje@cs.tcd.ie

Supplementary information: http://www.cs.tcd.ie/Francisco.Azuaje/Cval.html
Structure motif discovery and mining the PDB
Authors: Jonassen Inge , Eidhammer Ingvar , Conklin Darrell , Taylor William R.
Published: July 2002

Motivation: Many of the most interesting functional and evolutionary relationships among proteins are so ancient that they cannot be reliably detected through sequence analysis and are apparent only through a comparison of the tertiary structures. The conserved features can often be described as structural motifs consisting of a few single residues or Secondary Structure (SS) elements. Confidence in such motifs is greatly boosted when they are found in more than a pair of proteins.

Results: We describe an algorithm for the automatic discovery of recurring patterns in protein structures. The patterns consist of individual residues having a defined order along the protein’s backbone that come close together in the structure and whose spatial conformations are similar. The residues in a pattern need not be close in the protein’s sequence. The work described in this paper builds on an earlier reported algorithm for motif discovery. This paper describes a significant improvement of the algorithm which makes it very efficient. The improved efficiency allows us to use it for doing unsupervised learning of patterns occurring in small subsets in a large set of structures, a non-redundant subset of the Protein Data Bank (PDB) database of all known protein structures.

Availability: The program is freely available to academia, requests can be sent to Inge.Jonassen@ii.uib.no.

Contact: Inge.Jonassen@ii.uib.no

* To whom correspondence should be addressed.
Measuring the Economic Effects of Military Base Closures
Authors: Hooker Mark A. , Knetter Michael M.
Published: July 2002

In this article, we use a newly constructed dataset to analyze the county‐level employment and personal income effects resulting from closures of military bases during 1971–94. Our estimated multipliers are mostly less than one, and considerably smaller than those typically used in economic impact studies. We find that the employment costs are mostly limited to the direct job loss associated with military transfers out of the region, and per capita income is little affected by closures on average.
De novo‐synthesized ceramide signals apoptosis in astrocytes via extracellular signal‐regulated kinase
Authors: BLÁZQUEZ CRISTINA , GALVE‐ROPERH ISMAEL , GUZMÁN MANUEL
Published: July 2002

ABSTRACT Recent observations support the importance of ceramide synthesis de novo in the induction of apoptosis. However, the downstream targets of de novo‐synthesized ceramide are unknown. Here we show that palmitate incorporated into ceramide and induced apoptotic DNA fragmentation in astrocytes. These effects of palmitate were exacerbated when fatty acid breakdown was uncoupled and were not evident in neurons, which show a very low capacity to take up and metabolize palmitate. Palmitate‐induced apoptosis of astrocytes was prevented by L‐cycloserine and fumonisin B1, two inhibitors of ceramide synthesis de novo, and by PD098059, an inhibitor of the extracellular signal‐regulated kinase (ERK) cascade. Accordingly, palmitate activated ERK by a process that was dependent on ceramide synthesis de novo and Raf‐1, but independent of kinase suppressor of Ras. Other potential targets of ceramide in the control of cell fate, namely, c‐Jun amino‐terminal kinase, p38 mitogen‐activated protein kinase, and protein kinase B, were not significantly affected in astrocytes exposed to palmitate. Results show that the Raf‐1/ERK cascade is the selective downstream target of de novo‐synthesized ceramide in the induction of apoptosis in astrocytes and also highlight the importance of ceramide synthesis de novo in apoptosis of astrocytes, which might have pathophysiological relevance.—Blázquez, C., Galve‐Roperh, I., Guzmán, M. De novo‐synthesized ceramide signals apoptosis in astrocytes via extracellular signal‐regulated kinase. FASEB J. 14, 2315‐2322 (2000)
Carbon dioxide starvation, the development of C4 ecosystems, and mammalian evolution
Authors: Cerling T. E. , Ehleringer J. R. , Harris J. M.
Published: July 2002

The decline of atmospheric carbon dioxide over the last 65 million years (Ma) resulted in the ‘carbon dioxide–starvation’ of terrestrial ecosystems and led to the widespread distribution of C
4
plants, which are less sensitive to carbon dioxide levels than are C
3
plants. Global expansion of C
4
biomass is recorded in the diets of mammals from Asia, Africa, North America, and South America during the interval from about 8 to 5 Ma. This was accompanied by the most significant Cenozoic faunal turnover on each of these continents, indicating that ecological changes at this time were an important factor in mammalian extinction. Further expansion of tropical C
4
biomass in Africa also occurred during the last glacial interval confirming the link between atmospheric carbon dioxide levels and C
4
biomass response. Changes in fauna and flora at the end of the Miocene, and between the last glacial and interglacial, have previously been attributed to changes in aridity; however, an alternative explanation for a global expansion of C
4
biomass is carbon dioxide starvation of C
3
plants when atmospheric carbon dioxide levels dropped below a threshold significant to C
3
plants. Aridity may also have been a factor in the expansion of C
4
ecosystems but one that was secondary to, and perhaps because of, gradually decreasing carbon dioxide concentrations in the atmosphere. Mammalian evolution in the late Neogene, then, may be related to the carbon dioxide starvation of C
3
ecosystems.
Rates of speciation in the fossil record
Authors: John Sepkoski J.
Published: July 2002

Data from palaeontology and biodiversity suggest that the global biota should produce an average of three new species per year. However, the fossil record shows large variation around this mean. Rates of origination have declined through the Phanerozoic. This appears to have been largely a function of sorting among higher taxa (especially classes), which exhibit characteristic rates of speciation (and extinction) that differ among them by nearly an order of magnitude. Secular decline of origination rates is hardly constant, however; many positive deviations reflect accelerated speciation during rebounds from mass extinctions. There has also been general decline in rates of speciation within major taxa through their histories, although rates have tended to remain higher among members in tropical regions. Finally, pulses of speciation appear sometimes to be associated with climate change, although moderate oscillations of climate do not necessarily promote speciation despite forcing changes in species' geographical ranges.
Challenges with managing insecticide resistance in agricultural pests, exemplisfied by the whitefly Bemisia tabaci
Authors: Denholm I. , Cahill M. , Dennehy T. J. , Horowitz A. R.
Published: July 2002

For many key agricultural pests, successful management of insecticide resistance depends not only on modifying the way that insecticides are deployed, but also on reducing the total number of treatments applied. Both approaches benefit from a knowledge of the biological characteristics of pests that promote or may retard the development of resistance. For the whitefly
Bemisia tabaci
(Gennadius), these factors include a haplodiploid breeding system that encourages the rapid selection and fixation of resistance genes, its breeding cycle on a succession of treated or untreated hosts, and its occurrence on and dispersal from high–value crops in greenhouses and glasshouses. These factors, in conjunction with often intensive insecticide use, have led to severe and widespread resistance that now affects several novel as well as conventional control agents. Resistance–management strategies implemented on cotton in Israel, and subsequently in south–western USA, have nonetheless so far succeeded in arresting the resistance treadmill in
B. tabaci
through a combination of increased chemical diversity, voluntary or mandatory restrictions on the use of key insecticides, and careful integration of chemical control with other pest–management options. In both countries, the most significant achievement has been a dramatic reduction in the number of insecticide treatments applied against whiteflies on cotton, increasing the prospect of sustained use of existing and future insecticides.
Early medieval cattle remains from a Scandinavian settlement in Dublin: genetic analysis and comparison with extant breeds
Authors: MacHugh David E. , Troy Christopher S. , McCormick Finbar , Olsaker Ingrid , Eythórsdóttir Emma , Bradle Daniel G.
Published: July 2002

A panel of cattle bones excavated from the 1000–year–old Viking Fishamble Street site in Dublin was assessed for the presence of surviving mitochondrial DNA (mtDNA). Eleven of these bones gave amplifiable mtDNA and a portion of the hypervariable control region was determined for each specimen. A comparative analysis was performed with control region sequences from five extant Nordic and Irish cattle breeds. The medieval population displayed similar levels of mtDNA diversity to modern European breeds. However, a number of novel mtDNA haplotypes were also detected in these bone samples. In addition, the presence of a putative ancestral sequence at high frequency in the medieval population supports an early post–domestication expansion of cattle in Europe.
Functional genomics: lessons from yeast
Authors: Oliver Stephen G.
Published: July 2002

Functional genomics represents a systematic approach to elucidating the function of the novel genes revealed by complete genome sequences. Such an approach should adopt a hierarchical strategy since this will both limit the number of experiments to be performed and permit a closer and closer approximation to the function of any individual gene to be achieved. Moreover, hierarchical analyses have, in their early stages, tremendous integrative power and functional genomics aims at a comprehensive and integrative view of the workings of living cells. The first draft of the human genome sequence has just been produced, and the complete genome sequences of a number of eukaryotic human pathogens (including the parasitic protozoaPlasmodium, Leishmania,andTrypanosoma) will soon be available. However, the most rapid progress in the elucidation of gene function will initially be made using model organisms. Yeast is an excellent eukaryotic model and at least 40% of single–gene determinants of human heritable diseases find homologues in yeast. We have adopted a systematic approach to the functional analysis of theSaccharomyces cerevisiaegenome. A number of the approaches for the functional analysis of novel yeast genes are discussed. The different approaches are grouped into four domains: genome, transcriptome, proteome, and metabolome. The utility of genetic, biochemical, and physico–chemical methods for the analysis of these domains is discussed, and the importance of framing precise biological questions, when using these comprehensive analytical methods, is emphasized. Finally, the prospects for elucidating the function of protozoan genes by using the methods pioneered with yeast, and even exploitingSaccharomycesitself, as a surrogate, are explored.
Patterns of Human Diversity, within and among Continents, Inferred from Biallelic DNA Polymorphisms
Authors: Romualdi Chiara , Balding David , Nasidze Ivane S. , Risch Gregory , Robichaux Myles , Sherry Stephen T. , Stoneking Mark , Batzer Mark A. , Barbujani Guido
Published: July 2002

Previous studies have reported that about 85% of human diversity at Short Tandem Repeat (STR) and Restriction Fragment Length Polymorphism (RFLP) autosomal loci is due to differences between individuals of the same population, whereas differences among continental groups account for only 10% of the overall genetic variance. These findings conflict with popular notions of distinct and relatively homogeneous human races, and may also call into question the apparent usefulness of ethnic classification in, for example, medical diagnostics. Here, we present new data on 21 Alu insertions in 32 populations. We analyze these data along with three other large, globally dispersed data sets consisting of apparently neutral biallelic nuclear markers, as well as with a β-globin data set possibly subject to selection. We confirm the previous results for the autosomal data, and find a higher diversity among continents for Y-chromosome loci. We also extend the analyses to address two questions: (1) whether differences between continental groups, although small, are nevertheless large enough to confidently assign individuals to their continent on the basis of their genotypes; (2) whether the observed genotypes naturally cluster into continental or population groups when the sample source location is ignored. Using a range of statistical methods, we show that classification errors are at best around 30% for autosomal biallelic polymorphisms and 27% for the Y chromosome. Two data sets suggest the existence of three and four major groups of genotypes worldwide, respectively, and the two groupings are inconsistent. These results suggest that, at random biallelic loci, there is little evidence, if any, of a clear subdivision of humans into biologically defined groups.
Simultaneous optimization of beam orientations and beam weights in conformal radiotherapy
Authors: Rowbottom Carl Graham , Khoo Vincent S. , Webb Steve
Published: July 2002

A methodology for the concurrent optimization of beam orientations and beam weights in conformal radiotherapy treatment planning has been developed and tested on a cohort of five patients. The algorithm is based on a beam‐weight optimization scheme with a downhill simplex optimization engine. The use of random voxels in the dose calculation provides much of the required speed up in the optimization process, and allows the simultaneous optimization of beam orientations and beam weights in a reasonable time. In the implementation of the beam‐weight optimization algorithm just 10% of the original patient voxels are used for the dose calculation and cost function evaluation. A fast simulated annealing algorithm controls the optimization of the beam arrangement. The optimization algorithm was able to produce clinically acceptable plans for the five patients in the cohort study. The algorithm equalized the dose to the optic nerves compared to the standard plans and reduced the mean dose to the brain stem by an average of 4.4% (±1.9, 1 SD), p The dose distribution to the PTV was not compromised by developing beam arrangements via the optimization algorithm. In conclusion, the simultaneous optimization of beam orientations and beam weights has been developed to be routinely used in a realistic time. The results of optimization in a small cohort study show that the optimization can reliably produce clinically acceptable dose distributions and may be able to improve dose distributions compared to those from a human planner.
Determining parameters for respiration‐gated radiotherapy
Authors: Vedam S. S. , Keall P. J. , Kini V. R. , Mohan R.
Published: July 2002

Respiration‐gated radiotherapy for tumor sites affected by respiratory motion will potentially improve radiotherapy outcomes by allowing reduced treatment margins leading to decreased complication rates and/or increased tumor control. Furthermore, for intensity‐modulated radiotherapy (IMRT), respiratory gating will minimize the hot and cold spot artifacts in dose distributions that may occur as a result of interplay between respiratory motion and leaf motion. Most implementations of respiration gating rely on the real time knowledge of the relative position of the internal anatomy being treated with respect to that of an external marker. A method to determine the amplitude of motion and account for any difference in phase between the internal tumor motion and external marker motion has been developed. Treating patients using gating requires several clinical decisions, such as whether to gate during inhale or exhale, whether to use phase or amplitude tracking of the respiratory signal, and by how much the intrafraction tumor motion can be decreased at the cost of increased delivery time. These parameters may change from patient to patient. A method has been developed to provide the data necessary to make decisions as to the CTV to PTV margins to apply to a gated treatment plan.
Laser‐based microfocused x‐ray source for mammography: Feasibility study
Authors: Krol A. , Ikhlef A. , Kieffer J. C. , Bassano D. A. , Chamberlain C. C. , Jiang Z. , Pépin H. , Prasad S. C.
Published: July 2002

A laser‐produced plasma (LPP) x‐ray source with possible application in mammography was created by focusing a laser beam on a Mo target. A Table‐Top‐Terawatt (TTT) laser operating at 1 J energy per pulse was employed. A dual pulse technique was used. Maximum energy transfer from laser light to hot electrons was reached at a 150 ps delay between pulses and the conversion efficiency (hard x‐ray yield/laser energy input) was The created LPP x‐ray source is characterized by a very small focal spot size (tens of μm), Gaussian brightness distribution, and a very short pulse duration (a few ps). The spectral distribution of the generated x rays was measured. Images of the focal spot, using a pinhole camera, and images of a resolution pattern and a mammographic phantom were obtained. The LPP focal spot modulation transfer function for different magnification factors was calculated. We have shown that the LPP source in conjunction with a spherically bent, high throughput, crystal monochromator in a fixed‐exit Rowland circle configuration can be used to create a narrow band tunable mammography system. Tunability to a specific patient breast tissue thickness and density would allow one to significantly improve contrast and resolution (exceeding 20 lp/mm) while lowering the exposure up to 50% for thicker breasts. The prospects for the LPP x‐ray source for mammographic application are discussed.
Marie and Pierre Curie and radium: History, mystery, and discovery
Authors: Mould R. F.
Published: July 2002

Commencing with Marie Curie's early life in Poland and the discovery of radium in the rue l'Homond “shed” in Paris in 1898, this paper includes some little known facts. It ends with some unusual uses of and claims for radium, and finally, because Medical Physics is an American journal, details are included of Marie Curie's two visits to the USA.
Intensity modulated radiotherapy with charged particle beams: Studies of inverse treatment planning for rotation therapy
Authors: Oelfke U. , Bortfeld T.
Published: July 2002

The optimization of intensity modulated radiotherapy (IMRT) for charged particle beams is a necessary prerequisite to evaluate the clinical potential of this treatment modality in comparison to IMRT with high energy photons. A theoretical study for IMRT with charged particle beams delivered by rotation therapy is presented. First, the inverse problem for two‐dimensional rotation therapy with arbitrary depth dose curves is formulated. Then a numerical strategy is devised to calculate fluence profiles for the simplified case of arbitrary rotationally invariant dose distributions. This mathematical framework is applied to study various aspects of charged particle IMRT. A central topic of the investigation is the evaluation of dose delivery, based on distal edge tracking (DET) and intensity modulation. The potential of DET‐IMRT with charged particle beams is studied in comparison to an optimal, conventional dose delivery technique, which employs the concept of a spread‐out Bragg peak (SOBP). Moreover, a comparison to photon IMRT is provided for simple geometric dose patterns. The technique of DET‐IMRT for the delivery of a homogeneous target dose is only feasible for targets up to a critical radius, depending on the individual shape of the employed Bragg peak. The irradiation of larger targets requires energy modulation in addition to the range modulation for DET. The accurate placement of the Bragg peak with respect to the target edge is found to be of potential importance. Comparing dose delivery via DET‐IMRT with the optimal SOBP technique revealed a significant advantage of DET‐IMRT, especially a saved integral dose in target‐adjacent healthy tissues of up to 30%, and a reduction of the penumbra at the target edge by almost 50%. A saving in integral dose to healthy tissues by a factor of 2–3 was observed for DET‐IMRT in comparison to IMRT with high energy photons.
The physics of golf: The convex face of a driver
Authors: Penner A. Raymond
Published: July 2002

The impact of the clubhead of a driver with a golf ball is modeled. The effect of the convex clubface of a driver on the flight of the golf ball is considered and the dependence of the optimum curvature of the clubface on the volume, mass, and impact speed of the clubhead is determined.
What if entropy were dimensionless?
Authors: Leff Harvey S.
Published: July 2002

One of entropy’s puzzling aspects is its dimensions of energy/temperature. A review of thermodynamics and statistical mechanics leads to six conclusions: (1) Entropy’s dimensions are linked to the definition of the Kelvin temperature scale. (2) Entropy can be defined to be dimensionless when temperature T is defined as an energy (dubbed tempergy). (3) Dimensionless entropy per particle typically is between 0 and ∼80. Its value facilitates comparisons among materials and estimates of the number of accessible states. (4) Using dimensionless entropy and tempergy, Boltzmann’s constant k is unnecessary. (5) Tempergy, kT, does not generally represent a stored system energy. (6) When the (extensive) heat capacity C≫k, tempergy is the energy transfer required to increase the dimensionless entropy by unity.
Spin coherent states as anticipators of the geometric phase
Authors: Aravind P. K.
Published: July 2002

Spin coherent states, proposed by several workers in the early 70s, are shown to contain the natural generalization to higher spins of the phase discovered earlier by Pancharatnam for polarized light. They also provide a simple setting in which the geometric phase of Berry and of Aharonov and Anandan can be exhibited and some of its further properties, noted by Samuel and Bhandari, can be illustrated. It is pointed out how many of the foregoing results might have been deduced in the 70s by proceeding in strict analogy with the earlier work of Pancharatnam. A similar point is made in connection with the geometric phase of SU(1,1) coherent states. In addition to its possible historical interest, this approach shows how the concept of the geometric phase can be introduced and developed in a largely kinematic fashion as an addendum to the standard quantum theory of angular momentum.
Magnetic field calculation for arbitrarily shaped planar wires
Authors: Miranda José A.
Published: July 2002

It is common to use the Biot–Savart law as a tool to explicitly calculate the magnetic field due to currents flowing in simply shaped wires such as circular loops and straight lines. In this work, by using the Biot–Savart law and its inherent geometric properties, we derive a very simple integral expression that allows a straightforward computation of the magnetic field due to arbitrarily shaped planar current-carrying wires, at a point that lies in the same plane as the current filament. Such an expression is conveniently written in terms of the wire’s shape r=r(θ). We illustrate the usefulness of our result by calculating the magnetic field at specific points in the wire’s plane due to currents flowing in conic curves, spirals, and harmonically deformed circular circuits. Relevant asymptotic behavior is calculated in various limits of interest.
In vitro measurement of the frequency-dependent attenuation in cancellous bone between 0.2 and 2 MHz
Authors: Chaffaı̈ Sana , Padilla Fréderic , Berger Geneviève , Laugier Pascal
Published: July 2002

Our goal was to evaluate the frequency dependence of the ultrasonic attenuation coefficient in cancellous bone. Estimates were obtained in immersion, using a substitution method in the through-transmit mode, by scanning 14 human bone specimens (calcaneus). Measurements were performed with three pairs of focused transducers with a center frequency of 0.5, 1.0, and 2.25 MHz, respectively in order to cover an extended frequency bandwidth (0.2–1.7 MHz). When the experimental attenuation coefficient values were modeled with a nonlinear power fit α(f )=α0+α1fn, the attenuation coefficient was found to increase as f1.09±0.3 over the measurement bandwidth. However, a substantial variation of the exponent n (0.4–2.2) within specimens and also between specimens was observed. The acoustical parameters were compared to bone mineral density. A highly significant relationship was noted between α1 and BMD (r2=0.75, p<10−4). No correlation was found between n and BMD. Several attenuation mechanisms are discussed as well as the potential impact these results may have in in vivo quantitative measurements.
Method to resolve microphone and sample location errors in the two-microphone duct measurement method
Authors: Katz Brian F. G.
Published: July 2002

Utilizing the two-microphone impedance tube method, the normal incidence acoustic absorption and acoustic impedance can be measured for a given sample. This method relies on the measured transfer function between two microphones, and the knowledge of their precise location relative to each other and the sample material. In this article, a method is proposed to accurately determine these locations. A third sensor is added at the end of the tube to simplify the measurement. First, a justification and investigation of the method is presented. Second, reference terminations are measured to evaluate the accuracy of the apparatus. Finally, comparisons are made between the new method and current methods for determining these distances and the variations are discussed. From this, conclusions are drawn with regards to the applicability and need for the new method and under which circumstances it is applicable. Results show that the method provides a reliable determination of both microphone locations, which is not possible using the current techniques. Errors due to inaccurate determination of these parameters between methods were on the order of 3% for |R| and 12% for Re {Z}.
Auditory scene analysis by echolocation in bats
Authors: Moss Cynthia F. , Surlykke Annemarie
Published: July 2002

Echolocating bats transmit ultrasonic vocalizations and use information contained in the reflected sounds to analyze the auditory scene. Auditory scene analysis, a phenomenon that applies broadly to all hearing vertebrates, involves the grouping and segregation of sounds to perceptually organize information about auditory objects. The perceptual organization of sound is influenced by the spectral and temporal characteristics of acoustic signals. In the case of the echolocating bat, its active control over the timing, duration, intensity, and bandwidth of sonar transmissions directly impacts its perception of the auditory objects that comprise the scene. Here, data are presented from perceptual experiments, laboratory insect capture studies, and field recordings of sonar behavior of different bat species, to illustrate principles of importance to auditory scene analysis by echolocation in bats. In the perceptual experiments, FM bats (Eptesicus fuscus) learned to discriminate between systematic and random delay sequences in echo playback sets. The results of these experiments demonstrate that the FM bat can assemble information about echo delay changes over time, a requirement for the analysis of a dynamic auditory scene. Laboratory insect capture experiments examined the vocal production patterns of flying E. fuscus taking tethered insects in a large room. In each trial, the bats consistently produced echolocation signal groups with a relatively stable repetition rate (within 5%). Similar temporal patterning of sonar vocalizations was also observed in the field recordings from E. fuscus, thus suggesting the importance of temporal control of vocal production for perceptually guided behavior. It is hypothesized that a stable sonar signal production rate facilitates the perceptual organization of echoes arriving from objects at different directions and distances as the bat flies through a dynamic auditory scene. Field recordings of E. fuscus, Noctilio albiventris, N. leporinus, Pippistrellus pippistrellus, and Cormura brevirostris revealed that spectral adjustments in sonar signals may also be important to permit tracking of echoes in a complex auditory scene.
Sources of variation in profile analysis. II. Component spacing, dynamic changes, and roving level
Authors: Drennan Ward R. , Watson Charles S.
Published: July 2002

Profile-analysis experiments have typically employed static profiles with constant frequency components spaced at equal intervals along a logarithmic frequency axis. Most periodic, naturally occurring stimuli, however, have components that are harmonically related and vary dynamically in time. One goal of these studies was to determine whether amplitude-increment detection thresholds are different in dynamic, harmonically spaced profiles compared to those for static-log profiles, and why such differences might exist. A second goal was to determine the impact of roving levels (within-trial variation of level). Thresholds for static-log profiles were, on average, 8.7 dB lower than for static-harmonic profiles. A traditional filter-bank model could not account for this result. No consistent effect of dynamic contour (an exponential rising frequency glide) was observed. Thresholds were consistently poorer by 4 to 7 dB when the level was roved, but the differences in thresholds among the different profiles varied little. It is proposed that the higher thresholds observed in static-harmonic profiles may be accounted for by the more intense pitch strength associated with the harmonic profiles.
Comparison of electrode discrimination, pitch ranking, and pitch scaling data in postlingually deafened adult cochlear implant subjects
Authors: Collins Leslie M. , Zwolan Teresa A. , Wakefield Gregory H.
Published: July 2002

The goal of this study was to investigate the relationship between variation in electrode site of stimulation and the perceptual dimensions along which such stimuli vary. This information may allow more effective use of electrode place when encoding speech information. To achieve this goal, two procedures which measure pitch in subjects implanted with the Nucleus/Cochlear Corporation multichannel device were performed. Estimates of electrode discriminability that can be obtained from these procedures were compared to a more direct measure of electrode discriminability that was obtained in a previous study [Collins et al., Assoc. Res. Otolaryng. Abstracts, No. 642 (1994)]. In the first task, subjects performed a pitch ranking procedure similar to that used in previous studies [Townshend et al., J. Acoust. Soc. Am. 82, 106–115 (1987); Nelson et al., J. Acoust. Soc. Am. 98, 1987–1999 (1995)]. Estimates of the pitch percept elicited by stimulation of each electrode as well as the discriminability of the electrodes were generated from the data using two different statistical analyses. In the second task, subjects performed a pitch scaling procedure similar to one used in a previous study [Busby et al., J. Acoust. Soc. Am. 95, 2658–2669 (1994)]. Again, two different statistical analyses were performed to generate estimates of the pitch percept corresponding to stimulation of each electrode and to generate estimates of electrode discriminability. In general, the estimates of the relationships between the pitch percepts obtained from the two procedures were not identical. In addition, the estimates of electrode discriminability were not equivalent to the electrode discrimination measures obtained from the same subjects during the previous study. Signal detection theory has been used to model the decision processes required by each of the procedures described above [e.g., Jesteadt and Bilger, J. Acoust. Soc. Am. 55, 1266–1276 (1974)]. However, these models do not predict the differences that were observed between the data sets obtained during this study. An alternate model is proposed which may explain the data obtained from these subjects. This model is based on the assumption that the percept that is elicited by electrical stimulation of an electrode is multidimensional, as opposed to unidimensional in nature. Therefore, the perceived signal is more appropriately modeled using a multidimensional random vector, where each element of the vector represents the perceived value of one of the dimensions of the signal.
Segment-based automatic language identification
Authors: Hazen Timothy J. , Zue Victor W.
Published: July 2002

This paper discusses the formulation, development and analysis of a segment-based approach to the automatic language identification (LID) problem. This system utilizes phonotactic, acoustic-phonetic, and prosodic information within a unified probabilistic framework. The implementation of this framework allows the relative contributions of different sources of information to be determined empirically, as well as providing the mechanism for combining them within one system. The system has been evaluated using the Oregon Graduate Institute (OGI) multi-language telephone speech corpus and the results are competitive with other current LID systems. The results have also indicated that, while the phontotactic information of a spoken utterance is the most useful information for LID, acoustic-phonetic and prosodic information can be useful for increasing a system’s accuracy, especially when the utterance is short.
Sound scattering by an air bubble near a plane sea surface
Authors: Ye Zhen , Feuillade Christopher
Published: July 2002

This paper presents a study of low-frequency sound scattering by an air bubble near a flat pressure-release surface. Using a self-consistent approach to describe multiple-scattering interactions, and a monopole approximation for the individual scatterer, the complete scattering amplitude for a bubble near a surface is derived. Radiation, thermal, and viscous damping effects are incorporated. The method leads to simple theoretical expressions which show that the presence of the surface modifies the resonance frequency and damping of the bubble, and modulates the scattering amplitude. The analytic formula for the modified resonance frequency compares favorably with earlier theoretical results, and with experimental data reported by M. Strasberg [J. Acoust. Soc. Am. 25, 536–537 (1953)]. At off-resonance frequencies, when the bubble is close to the surface and thermal and viscous dampings are not included, the results obtained agree with those of the modal series solution presented by Gaunaurd and Huang [IEEE J. Ocean. Eng. 20, 285–295 (1995)]. The two methods disagree at resonance frequencies, however, since the present approach predicts that the value of the scattering amplitude should decrease as the bubble is moved closer to the surface. This feature remains even when thermal and viscous dampings are not included. When the bubble is moved further away from the surface, oscillations appear in the scattering amplitude, in full accordance with the Lloyd’s mirror effect.
Double-evoked otoacoustic emissions. I. Measurement theory and nonlinear coherence
Authors: Keefe Douglas H.
Published: July 2002

An evoked otoacoustic emission (OAE) measurement technique is proposed to better control for probe distortion. Each double-evoking (2E) stimulus sequence includes three, equal-duration subsequences defined as follows: s1(t) is a single chirp or click, s2(t)=εs1(t−τ) is a copy of s1 with relative amplitude ε and delay τ, and s12(t)=s1(t)+s2(t) is the superposition of the first two stimuli. The pressure response to each subsequence is p1, p2, and p12, respectively. The double chirp-evoked distortion product (2ChDP) and double click-evoked otoacoustic emission (2CEOAE) are defined by pD=p12−(p1+p2). The 2ChDP response may be time compressed to analyze as an equivalent 2CEOAE response. The 2E response family provides a complementary representation between DP measurements and double click-evoked OAE measurements. A technique based on nonlinear coherence quantifies random noise in terms of a nonlinear signal-to-noise ratio.