bluuebunny/crossref_metadata_2025 huggingface dataset:
On the representation theory of Iwahori-Hecke algebras of extended finite Weyl groups
Authors: Geck Meinolf
Published: July 2002

We apply Lusztig’s theory of cells and asymptotic algebras to the Iwahori–Hecke algebra of a finite Weyl group extended by a group of graph automorphisms. This yields general results about splitting fields (extending earlier results by Digne–Michel) and decomposition matrices (generalizing earlier results by the author). Our main application is to establish an explicit formula for the number of simple modules in typeDnD_n(except in characteristic 22), using the known results about typeBnB_ndue to Dipper, James, and Murphy and Ariki and Mathas.
On Laguerre polynomials, Bessel functions, Hankel transform and a series in the unitary dual of the simply-connected covering group of 𝑆𝑙(2,ℝ)
Authors: Kostant Bertram
Published: July 2002

Analogous to the holomorphic discrete series ofSl(2,R)Sl(2,\mathbb R)there is a continuous family{πr}\{\pi _r\},−1>r>∞-1>r>\infty, of irreducible unitary representations ofGG, the simply-connected covering group ofSl(2,R)Sl(2,\mathbb R). A construction of this series is given in this paper using classical function theory. For allrrthe Hilbert space isL2((0,∞))L_2((0,\infty )). First of all one exhibits a representation,DrD_r, ofg=LieG\mathfrak g=Lie\,Gby second order differential operators onC∞((0,∞))C^\infty ((0,\infty )). Forx∈(0,∞)x\in (0,\infty ),−1>r>∞-1>r>\inftyandn∈Z+n\in \mathbb Z_+let<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="phi Subscript n Superscript left-parenthesis r right-parenthesis Baseline left-parenthesis x right-parenthesis equals e Superscript negative x Baseline x Superscript StartFraction r Over 2 EndFraction Baseline upper L Subscript n Superscript left-parenthesis r right-parenthesis Baseline left-parenthesis 2 x right-parenthesis">φn(r)(x)=e−xxr2Ln(r)(2x)\varphi _n^{(r)}(x)= e^{-x}x^{\frac {r}{2}}L_n^{(r)}(2x)whereLn(r)(x)L_n^{(r)}(x)is the Laguerre polynomial with parameters{n,r}\{n,r\}. LetHrHC\mathcal H_r^{HC}be the span ofφn(r)\varphi _n^{(r)}forn∈Z+n\in \mathbb Z_+. Next one shows, using a famous result of E. Nelson, thatDr|HrHCD_r|{\mathcal H}_r^{HC}exponentiates to the unitary representationπr\pi _rofGG. The power of Nelson’s theorem is exhibited here by the fact that if0>r>10>r>1, one hasDr=D−rD_r=D_{-r}, whereasπr\pi _ris inequivalent toπ−r\pi _{-r}. Forr=12r=\frac 12, the elements in the pair{π12,π−12}\{\pi _{\frac {1}{2}},\pi _{-\frac {1}{2}}\}are the two components of the metaplectic representation. Using a result of G.H. Hardy one shows that the Hankel transform is given byπr(a)\pi _r(a)wherea∈Ga\in Ginduces the non-trivial element of a Weyl group. As a consequence, continuity properties and enlarged domains of definition, of the Hankel transform follow from standard facts in representation theory. Also, ifJrJ_ris the classical Bessel function, then for anyy∈(0,∞)y\in (0,\infty ), the functionJr,y(x)=Jr(2xy)J_{r,y}(x)=J_r(2\sqrt {xy})is a Whittaker vector. Other weight vectors are given and the highest weight vector is given by a limiting behavior at00.
Wall-crossing functors and 𝒟-modules
Authors: Beilinson Alexander , Ginzburg Victor
Published: July 2002

We study Translation functors and Wall-Crossing functors on infinite dimensional representations of a complex semisimple Lie algebra using

D

{\mathcal {D}}

-modules. This functorial machinery is then used to prove the Endomorphism-theorem and the Structure-theorem; two important results were established earlier by W. Soergel in a totally different way. Other applications to the category

O

{\mathcal {O}}

of Bernstein-Gelfand-Gelfand are given, and some conjectural relationships between Koszul duality, Verdier duality and convolution functors are discussed. A geometric interpretation of tilting modules is given.
Feature selection for genetic sequence classification.
Authors: Chuzhanova N A , Jones A J , Margetts S
Published: July 2002

MOTIVATION: Most of the existing methods for genetic sequence classification are based on a computer search for homologies in nucleotide or amino acid sequences. The standard sequence alignment programs scale very poorly as the number of sequences increases or the degree of sequence identity is <30%. Some new computationally inexpensive methods based on nucleotide or amino acid compositional analysis have been proposed, but prediction results are still unsatisfactory and depend on the features chosen to represent the sequences. RESULTS: In this paper, a feature selection method based on the Gamma (or near-neighbour) test is proposed. If there is a continuous or smooth map from feature space to the classification target values, the Gamma test gives an estimate for the mean-squared error of the classification, despite the fact that one has no a priori knowledge of the smooth mapping. We can search a large space of possible feature combinations for a combination which gives a smallest estimated mean-squared error using a genetic algorithm. The method was used for feature selection and classification of the large subunits of rRNA according to RDP (Ribosomal Database Project) phylogenetic classes. The sequences were represented by dinucleotide frequency distribution. The nearest-neighbour criterion has been used to estimate the predictive accuracy of the classification based on the selected features. For examples discussed, we found that the classification according to the first nearest neighbour is correct for 80% of the test samples. If we consider the set of the 10 nearest neighbours, then 94% of the test samples are classified correctly. AVAILABILITY: The principal novel component of this method is the Gamma test and this can be downloaded compiled for Unix Sun 4, Windows 95 and MS-DOS from http://www.cs.cf.ac.uk/ec/ Contact: s.margetts@cs.cf.ac.uk
Non‐coding RNAs: the architects of eukaryotic complexity
Authors: Mattick John S
Published: July 2002

Around 98% of all transcriptional output in humans is non‐coding RNA. RNA‐mediated gene regulation is widespread in higher eukaryotes and complex genetic phenomena like RNA interference, co‐suppression, transgene silencing, imprinting, methylation, and possibly position‐effect variegation and transvection, all involve intersecting pathways based on or connected to RNA signaling. I suggest that the central dogma is incomplete, and that intronic and other non‐coding RNAs have evolved to comprise a second tier of gene expression in eukaryotes, which enables the integration and networking of complex suites of gene activity. Although proteins are the fundamental effectors of cellular function, the basis of eukaryotic complexity and phenotypic variation may lie primarily in a control architecture composed of a highly parallel system oftrans‐acting RNAs that relay state information required for the coordination and modulation of gene expression, via chromatin remodeling, RNA–DNA, RNA–RNA and RNA–protein interactions. This system has interesting and perhaps informative analogies with small world networks and dataflow computing.
Collars and Consumers: Changing Images of American Manliness and Business
Authors: Turbin Carole
Published: July 2002

Detachable collars, essential to men’s appearance from the 1840s to the 1920s, have left a lasting legacy: the term ‘white collar’ and the “Arrow Man,” the centerpiece of Arrow collar advertisements from 1907 until 1931. The Arrow Man was the visual representation of the “New Man,” and Arrow collars were preserved in American culture through the lyrics of a 1934 Cole Porter song, “You’re the Top.” Both the Arrow collar and the Arrow Man derived from business decisions that reflected emerging and changing American consumer tastes and markets, an expanding middle class, and shifts in culture, especially in new ideal images of manliness that were less class-based, contributing to Americans’ impression that social distinctions were more blurred than in the past. The Arrow Man embodied in a single compelling image the resolution of social contradictions that persisted beneath the increased similarity of men of different backgrounds.
Extrapolating feedback processes from the present to the past
Authors: Raven J. A.
Published: July 2002

Extant terrestrial vegetation alters its physical environment via its albedo, and its influence on immediate temperature via stomatal and boundary–layer influences of energy dissipation as sensible and latent heat; aquatic vegetation also controls albedo (e.g. coccolithophorids) and, by competing with water for electromagnetic energy absorption, the depth of the mixed layer and hence the quantity of nutrients trapped for the spring bloom. Both aquatic and terrestrial vegetation have had, together with microbial and geological processes, an influence on O2and CO2levels, and hence on the availability and biological functioning of Fe, Mn, Cu, Zn, Se and P, and the relative competitive advantage of C3versus C4, crassulacean acid metabolism (CAM) and carbon concentration mechanism (CCM) organisms. Less directly, changes in primary productivity impact on the production of CH4and N2O which, like CO2, are greenhouse gases, while some (marine) primary producers yield dimethyl sulphide (and hence cloud condensation nuclei, with effects on cloudiness) and halocarbons (via, in part, O2–dependent processes), partly negating the O3attenuation of UV–B radiation. These effects can be related to the terrestrial embryophytic vegetation back to ca. 450 Ma, and to eukaryotic marine vegetation back to at least 1.7, and probably 2.1 Ga, with implications for inter alia C3versus C4, CAM and CCM photosynthesis, and Fe acquisition mechanisms. Even earlier (3.8 Ga onwards) prokaryotes may have influenced CO2levels and hence controlled (as they did later) surface temperature. By producing O2, they led to decreasing availability of Fe, Mn and P (and utility of Se?), and increasing availability of Cu (and Zn?) that shaped the biochemistry on which later biogeochemistry was based.
Nested biological variation and speciation
Authors: Foster Susan A. , Scott Robert J. , Cresko William A.
Published: July 2002

The modes of speciation that are thought to have contributed most to the generation of biodiversity require population differentiation as the initial stage in the speciation process. Consequently, a complete understanding of the mechanisms of speciation requires that the process be examined not just after speciation is complete, or nearly so, but also much earlier. Because reproductive isolation defines biological species, and it evolves slowly, study of the process may require a prohibitive span of time. Even if speciation could be observed directly, selection of populations in the process of speciation is typically difficult or impossible, because those that will ultimately undergo speciation cannot be distinguished from those that will differentiate but never assume the status of new biological species. One means of circumventing this problem is to study speciation in taxa comprising several sibling species, at least one of which exhibits extensive population differentiation. We illustrate this approach by exploring patterns of population variation in the post–glacial radiation of the threespine stickleback,Gasterosteus aculeatus. We focus on lacustrine populations and species within this complex, demonstrating parallel axes of divergence within populations, among populations and among species. The pattern that emerges is one of parallel relationships between phenotype and fitness at all three hierarchical levels, a pattern that facilitates exploration of the causes and consequences of speciation and secondary contact. A second outcome of this exploration is the observation that speciation can be the consequence of a cascade of effects, beginning with selection on trophic or other characteristics that in turn force the evolution of other population characteristics that precipitate speciation. Neither of these conclusions could have been reached without comparative studies of wild populations at several hierarchical levels, a conclusion reinforced by a brief survey of similar efforts to elucidate the process of speciation. We address the issues most likely to be resolved using this approach, and suggest that comparisons of natural variation within taxa at several hierarchical levels may substantially increase our understanding of the speciation process.
Rabies in Zimbabwe: reservoir dogs and the implications for disease control
Authors: Rhodes C. J. , Atkinson R. P. D. , Anderson R. M. , Macdonald D. W.
Published: July 2002

Using detailed field study observations of the side–striped jackal (Canis adustus) and a simple stochastic model of the transmission dynamics of the virus and host demography, we discuss the epidemiology of rabies virus infection in the jackal population of Zimbabwe. Of the two jackal species in Zimbabwe, the other being the black–backed jackal (Canis mesomelas), the bulk of notified rabies cases are in side–striped jackals. Specifically, we show that the side–striped jackal population itself does not seem able to support rabies infection endemically, i.e. without frequent reintroduction from outside sources of infection. We argue that this is probably because the overall average jackal population density is too low to maintain the chain of infection. This study suggests that the disease is regularly introduced to jackals by rabid dogs from populations associated with human settlements. Given the rapidly rising dog population in Zimbabwe, estimates are derived of the future incidence of jackal rabies based on different dog vaccination scenarios.
A two–stage model for Cepaea polymorphism
Authors: Cook L. M.
Published: July 2002

The history of the study of snails in the genusCepaeais briefly outlined.Cepaea nemoralisandC. hortensisare polymorphic for genetically controlled shell colour and banding, which has been the main interest of the work covered. Random drift, selective predation and climatic selection, both at a macro– and micro–scale, all affect gene frequency. The usual approach to understanding maintenance of the polymorphism, has been to look for centripetal effects on frequency. Possible processes include balance of mutation pressure and drift, heterozygote advantage, relational balance heterosis, frequency–dependent predation, multi–niche selective balance, or some combination of these. Mutational balance is overlaid by more substantial forces. There is some evidence for heterosis. Predation by birds may protect the polymorphism, and act apostatically to favour distinct morphs. Although not substantiated forCepaea, many studies show that predators behave in the appropriate manner, while shell colour polymorphisms in molluscs occur most commonly in species exposed to visually searching predators. It is not known whether different thermal properties of the shells help to generate equilibria. Migration between colonies is probably greater than originally thought. The present geographical range has been occupied for less than 5000 generations. Climatic and human modification alter snail habitats relatively rapidly, which in turn changes selection pressures. A simple simulation shows that migration coupled with selection which fluctuates but is not centripetal, may retain polymorphism for sufficiently long to account for the patterns we see today. There may therefore be a two–stage basis to the polymorphism, comprising long–term but weak balancing forces coupled with fluctuating selection which does not necessarily balance but results in very slow elimination. Persistence of genetic variants in this way may provide the conditions for evolution of a balanced genome.
An overview of the evolution of overproduced esterases in the mosquito Culex pipiens
Authors: Raymond M. , Chevillon C. , Guillemaud T. , Lenormand T. , Pasteur N.
Published: July 2002

Insecticide resistance genes have developed in a wide variety of insects in response to heavy chemical application. Few of these examples of adaptation in response to rapid environmental change have been studied both at the population level and at the gene level. One of these is the evolution of the overproduced esterases that are involved in resistance to organophosphate insecticides in the mosquitoCulex pipiens. At the gene level, two genetic mechanisms are involved in esterase overproduction, namely gene amplification and gene regulation. At the population level, the co–occurrence of the same amplified allele in distinct geographic areas is best explained by the importance of passive transportation at the worldwide scale. The long–term monitoring of a population of mosquitoes in southern France has enabled a detailed study to be made of the evolution of resistance genes on a local scale, and has shown that a resistance gene with a lower cost has replaced a former resistance allele with a higher cost.
Possible mechanisms of anosognosia: a defect in self–awareness
Authors:   The American Association for Research into Nervous and Mental Diseases, Heilman K. M. , Barrett A. M. , Adair J. C.
Published: July 2002

Anosognosia of hemiplegia is of interest for both pragmatic and theoretical reasons. We discuss several neuropsychological theories that have been proposed to explain this deficit. Although for psychological reasons people might deny deficits, the denial hypothesis cannot account for the hemispheric asymmetries associated with this disorder and cannot explain why some patients might deny one deficit and recognize another equally disabling deficit. There is some evidence that faulty feedback from sensory deficits, spatial neglect and asomatognosia might be responsible for anosognosia in some patients. However, these feedback hypotheses cannot account for anosognosia in all patients. Although the hemispheric disconnection hypothesis is appealing, disconnection is probably only a rare cause of this disorder. The feedforward intentional theory of anosognosia suggests that the discovery of weakness is dependent on attempted action and some patients might have anosognosia because they do not attempt to move. We present evidence that supports this theory. The presence of one mechanism of anosognosia, however, does not preclude the possibility that other mechanisms might also be working to produce this disorder. Although a large population study needs to be performed, we suspect that anosognosia might be caused by several of the mechanisms that we have discussed.

On the basis of the studies of impaired corporeal self–awareness that we have reviewed, we can infer that normal self–awareness is dependent on several parallel processes. One must have sensory feedback and the ability to attend to both one's body and the space where parts of the body may be positioned or acting. One must develop a representation of the body, and this representation must be continuously modified by expectations (feedforward) and knowledge of results (feedback).
The impact of molecular biology on neuroscience
Authors: Crick Francis
Published: July 2002

How our brains work is one of the major unsolved problems of biology. This paper describes some of the techniques of molecular biology that are already being used to study the brains of animals. Mainly as a result of the human genome project many new techniques will soon become available which could decisively influence the progress of neuroscience. I suggest that neuroscientists should tell molecular biologists what their difficulties are, in the hope that this will stimulate the production of useful new biological tools.
Introduction
Authors: Foyer Christine , Osmond Barry , Walker David
Published: July 2002

Research in photosynthesis continues to uncover surprising new phenomena. In these Discussion Meetings we drew attention to some of the paradigm shifts in contemporary research by concentrating on the importance of photoprotection, and of alternative photon and electron sinks, in the highly energetic primary processes of photosynthesis.We are most grateful to The Royal Society, and to the Novartis Foundation, for this opportunity to do so.
Evolutionary biology of language
Authors: Nowak Martin A.
Published: July 2002

Language is the most important evolutionary invention of the last few million years. It was an adaptation that helped our species to exchange information, make plans, express new ideas and totally change the appearance of the planet. How human language evolved from animal communication is one of the most challenging questions for evolutionary biology. The aim of this paper is to outline the major principles that guided language evolution in terms of mathematical models of evolutionary dynamics and game theory. I will discuss how natural selection can lead to the emergence of arbitrary signs, the formation of words and syntactic communication.
The evolution of replicators
Authors: Szathmáry Eörs
Published: July 2002

Replicators of interest in chemistry, biology and culture are briefly surveyed from a conceptual point of view. Systems with limited heredity have only a limited evolutionary potential because the number of available types is too low. Chemical cycles, such as the formose reaction, are holistic replicators since replication is not based on the successive addition of modules. Replicator networks consisting of catalytic molecules (such as reflexively autocatalytic sets of proteins, or reproducing lipid vesicles) are hypothetical ensemble replicators, and their functioning rests on attractors of their dynamics. Ensemble replicators suffer from the paradox of specificity: while their abstract feasibility seems to require a high number of molecular types, the harmful effect of side reactions calls for a small system size. No satisfactory solution to this problem is known. Phenotypic replicators do not pass on their genotypes, only some aspects of the phenotype are transmitted. Phenotypic replicators with limited heredity include genetic membranes, prions and simple memetic systems. Memes in human culture are unlimited hereditary, phenotypic replicators, based on language. The typical path of evolution goes from limited to unlimited heredity, and from attractor–based to modular (digital) replicators.
‘The surface management system’ (SuMS) database: a surface–based database to aid cortical surface reconstruction, visualization and analysis
Authors: Dickson James , Drury Heather , Van Essen David C.
Published: July 2002

Surface reconstructions of the cerebral cortex are increasingly widely used in the analysis and visualization of cortical structure, function and connectivity. From a neuroinformatics perspective, dealing with surface–related data poses a number of challenges. These include the multiplicity of configurations in which surfaces are routinely viewed (e.g. inflated maps, spheres and flat maps), plus the diversity of experimental data that can be represented on any given surface. To address these challenges, we have developed a surface management system (SuMS) that allows automated storage and retrieval of complex surface–related datasets.

SuMS provides a systematic framework for the classification, storage and retrieval of many types of surface–related data and associated volume data. Within this classification framework, it serves as a versioncontrol system capable of handling large numbers of surface and volume datasets. With built–in database management system support, SuMS provides rapid search and retrieval capabilities across all the datasets, while also incorporating multiple security levels to regulate access. SuMS is implemented in Java and can be accessed via a Web interface (WebSuMS) or using downloaded client software. Thus, SuMS is well positioned to act as a multiplatform, multi–user ‘surface request broker’ for the neuroscience community.
A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM)
Authors: Mazziotta John , Toga Arthur , Evans Alan , Fox Peter , Lancaster Jack , Zilles Karl , Woods Roger , Paus Tomas , Simpson Gregory , Pike Bruce , Holmes Colin , Collins Louis , Thompson Paul , MacDonald David , Iacoboni Marco , Schormann Thorsten , Amunts Katrin , Palomero-Gallagher Nicola , Geyer Stefan , Parsons Larry , Narr Katherine , Kabani Noor , Goualher Georges Le , Boomsma Dorret , Cannon Tyrone , Kawashima Ryuta , Mazoyer Bernard
Published: July 2002

Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four–dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono– and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post–mortem tissue to determine the probabilistic distribution of microscopic cyto– and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjectsin vivo, provides the first large scale opportunity to gain meaningful insights into the concordance or discordance in micro– and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype–phenotype–behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.
From teratocarcinomas to embryonic stem cells
Authors: Andrews Peter W.
Published: July 2002

The recent derivation of human embryonic stem (ES) cell lines, together with results suggesting an unexpected degree of plasticity in later, seemingly more restricted, stem cells (so–called adult stem cells), have combined to focus attention on new opportunities for regenerative medicine, as well as for understanding basic aspects of embryonic development and diseases such as cancer. Many of the ideas that are now discussed have a long history and much has been underpinned by the earlier studies of teratocarcinomas, and their embryonal carcinoma (EC) stem cells, which present a malignant surrogate for the normal stem cells of the early embryo. Nevertheless, although the potential of EC and ES cells to differentiate into a wide range of tissues is now well attested, little is understood of the key regulatory mechanisms that control their differentiation. Apart from the intrinsic biological interest in elucidating these mechanisms, a clear understanding of the molecular process involved will be essential if the clinical potential of these cells is to be realized. The recent observations of stem–cell plasticity suggest that perhaps our current concepts about the operation of cell regulatory pathways are inadequate, and that new approaches for analysing complex regulatory networks will be essential.
Chromosome-Specific Single-Locus FISH Probes Allow Anchorage of an 1800-Marker Integrated Radiation-Hybrid/Linkage Map of the Domestic Dog Genome to All Chromosomes
Authors: Breen Matthew , Jouquand Sophie , Renier Corinne , Mellersh Cathryn S. , Hitte Christophe , Holmes Nigel G. , Chéron Angélique , Suter Nicola , Vignaux Françoise , Bristow Anna E. , Priat Catherine , McCann E. , André Catherine , Boundy Sam , Gitsham Paul , Thomas Rachael , Bridge Wendy L. , Spriggs Helen F. , Ryder Ed J. , Curson Alistair , Sampson Jeff , Ostrander Elaine A. , Binns Matthew M. , Galibert Francis
Published: July 2002

We present here the first fully integrated, comprehensive map of the canine genome, incorporating detailed cytogenetic, radiation hybrid (RH), and meiotic information. We have mapped a collection of 266 chromosome-specific cosmid clones, each containing a microsatellite marker, to all 38 canine autosomes by fluorescence in situ hybridization (FISH). A 1500-marker RH map, comprising 1078 microsatellites, 320 dog gene markers, and 102 chromosome-specific markers, has been constructed using the RHDF5000-2 whole-genome radiation hybrid panel. Meiotic linkage analysis was performed, with at least one microsatellite marker from each dog autosome on a panel of reference families, allowing one meiotic linkage group to be anchored to all 38 dog autosomes. We present a karyotype in which each chromosome is identified by one meiotic linkage group and one or more RH groups. This updated integrated map, containing a total of 1800 markers, covers >90% of the dog genome. Positional selection of anchor clones enabled us, for the first time, to orientate nearly all of the integrated groups on each chromosome and to evaluate the extent of individual chromosome coverage in the integrated genome map. Finally, the inclusion of 320 dog genes into this integrated map enhances existing comparative mapping data between human and dog, and the 1000 mapped microsatellite markers constitute an invaluable tool with which to perform genome scanning studies on pedigrees of interest.
Free‐thiol Cys331 exposed during activation process is critical for native tetramer structure of cathepsin C (dipeptidyl peptidase I)
Authors: Horn Martin , Baudyš Miroslav , Voburka Zdeněk , Kluh Ivan , Vondrášek Jiří , Mareš Michael
Published: July 2002

The mature bovine cathepsin C (CC) molecule is composed of four identical monomers, each proteolytically processed into three chains. Five intrachain disulfides and three nonpaired cysteine residues per monomer were identified. Beside catalytic Cys234 in the active site, free‐thiol Cys331 and Cys424 were characterized. Cys424 can be classified as inaccessible buried residue. Selective modification of Cys331 results in dissociation of native CC tetramer into dimers. The 3D homology‐based model of the CC catalytic core suggests that Cys331 becomes exposed as the activation peptide is removed during procathepsin C activation. The model further shows that exposed Cys331 is surrounded by a surface hydrophobic cluster, unique to CC, forming a dimer–dimer interaction interface. Substrate/inhibitor recognition of the active site in the CC dimer differs significantly from that in the native tetramer. Taken together, a mechanism is proposed that assumes that the CC tetramer formation results in a site‐specific occlusion of endopeptidase‐like active site cleft of each CC monomeric unit. Thus, tetramerization provides for the structural basis of the dipeptidyl peptidase activity of CC through a substrate access‐limiting mechanism different from those found in homologous monomeric exopeptidases cathepsin H and B. In conclusion, the mechanism of tetramer formation as well as specific posttranslational processing segregates CC in the family of papain proteases.
Crystal structure of human L‐isoaspartyl‐O‐methyl‐transferase with S‐adenosyl homocysteine at 1.6‐Å resolution and modeling of an isoaspartyl‐containing peptide at the active site
Authors: Smith Craig D. , Carson Mike , Friedman Alan M. , Skinner Matthew M. , Delucas Lawrence , Chantalat Laurent , Weise Lance , Shirasawa Takuji , Chattopadhyay Debashish
Published: July 2002

Spontaneous formation of isoaspartyl residues (isoAsp) disrupts the structure and function of many normal proteins. Protein isoaspartyl methyltransferase (PIMT) reverts many isoAsp residues to aspartate as a protein repair process. We have determined the crystal structure of human protein isoaspartyl methyltransferase (HPIMT) complexed with adenosyl homocysteine (AdoHcy) to 1.6‐Å resolution. The core structure has a nucleotide binding domain motif, which is structurally homologous with the N‐terminal domain of the bacterial Thermotoga maritima PIMT. Highly conserved residues in PIMTs among different phyla are placed at positions critical to AdoHcy binding and orienting the isoAsp residue substrate for methylation. The AdoHcy is completely enclosed within the HPIMT and a conformational change must occur to allow exchange with adenosyl methionine (AdoMet). An ordered sequential enzyme mechanism is supported because C‐terminal residues involved with AdoHcy binding also form the isoAsp peptide binding site, and a change of conformation to allow AdoHcy to escape would preclude peptide binding. Modeling experiments indicated isoAsp groups observed in some known protein crystal structures could bind to the HPIMT active site.
Prostate boundary segmentation from 2D ultrasound images
Authors: Ladak Hanif M. , Mao Fei , Wang Yunqiu , Downey Dónal B. , Steinman David A. , Fenster Aaron
Published: July 2002

Outlining, or segmenting, the prostate is a very important task in the assignment of appropriate therapy and dose for cancer treatment; however, manual outlining is tedious and time‐consuming. In this paper, an algorithm is described for semiautomatic segmentation of the prostate from 2D ultrasound images. The algorithm uses model‐based initialization and the efficient discrete dynamic contour. Initialization requires the user to select only four points from which the outline of the prostate is estimated using cubic interpolation functions and shape information. The estimated contour is then deformed automatically to better fit the image. The algorithm can easily segment a wide range of prostate images, and contour editing tools are included to handle more difficult cases. The performance of the algorithm with a single user was compared to manual outlining by a single expert observer. The average distance between semiautomatically and manually outlined boundaries was found to be less than 5 pixels (0.63 mm), and the accuracy and sensitivity to area measurements were both over 90%.
Calculation of beta‐ray dose distributions from ophthalmic applicators and comparison with measurements in a model eye
Authors: Cross W. G. , Hokkanen J. , Järvinen H. , Mourtada F. , Sipilä P. , Soares C. G. , Vynckier S.
Published: July 2002

Dose distributions throughout the eye, from three types of beta‐ray ophthalmic applicators, were calculated using the EGS4, ACCEPT 3.0, and other Monte Carlo codes. The applicators were those for which doses were measured in a recent international intercomparison [Med. Phys. 28, 1373 (2001)], planar applicators ofandand a concaveapplicator. The main purpose was to compare the results of the various codes with average experimental values. For the planar applicators, calculated and measured doses on the source axis agreed within the experimental errors (<10%) to a depth of 7 mm forand 5 mm forAt greater distances the measured values are larger than those calculated. For the concaveapplicator, there was poor agreement among available calculations and only those calculated by ACCEPT 3.0 agreed with measured values. In the past, attempts have been made to derive such dose distributions simply, by integrating the appropriate point‐source dose function over the source. Here, we investigated the accuracy of this procedure for encapsulated sources, by comparing such results with values calculated by Monte Carlo. An attempt was made to allow for the effects of the silver source window but no corrections were made for scattering from the source backing. In these circumstances, at 6 mm depth, the difference in the results of the two calculations was 14%–18% for a planarapplicator and up to 30% for the concave applicator. It becomes worse at greater depths. These errors are probably caused mainly by differences between the spectrum of beta particles transmitted by the silver window and those transmitted by a thickness of water having the same attenuation properties.
Depth dose enhancement of electron beams subject to external uniform longitudinal magnetic fields: A Monte Carlo study
Authors: Earl M. A. , Ma L.
Published: July 2002

We studied the dose distributions from electron beams subjected to a longitudinal magnetic field applied to them before they reach the phantom. We found that specific combinations of the length and intensity of the magnetic field produced enhancement of the peaks of the central‐axis depth‐dose distributions. TheEGS4Monte Carlo system was used in this study. In the simulations, a uniform axial magnetic field parallel to the electron beam direction was applied to the air gap between the collimation and the phantom. We extensively studied the simplified case of an 18 MeV electron beam point source. Dose deposition was calculated for various magnetic field strengths, distances through which the magnetic field was applied, collimation sizes, and source to collimation distances. The magnetic field strengths varied from 0 to 3 T, the source‐to‐collimation distances studied were 50 and 95 cm, the collimation sizes studied were 10×10 and 20×20 cm2, and the distance through which the field was applied ranged from 10 to 20 cm. Specific combinations of these variables resulted in as much as a 70% enhancement of the peak dose relative to the surface dose. Finally, to determine how the geometry of a real accelerator affects the resulting dose distribution, we performed a full simulation of an Elekta SL20 linear accelerator and compared the results with the ideal case.
Computer analysis of mammography phantom images (CAMPI): An application to the measurement of microcalcification image quality of directly acquired digital images
Authors: Chakraborty Dev P.
Published: July 2002

The purpose of this investigation was to apply the recently developed CAMPI (computer analysis of mammography phantom images) method to a Fischer Mammotest Stereotactic Digital Biopsy machine. Another aim was to further elucidate the nature of the empirically introduced CAMPI measures. Images of an American College of Radiology (ACR) accreditation phantom centered on the largest two speck groups were obtained on this machine under a variety of x‐ray conditions. An additional measure, alternative SNR (ASNR) is introduced which is complementary to the SNR measure. Analyses of the Mammotest images revealed that the mAs and kVp dependencies of the CAMPI measures could be understood from basic imaging physics principles. It is shown that: (1) the measures reflect the expected linearity of the digital detector and Poisson photon statistics; (2) under automatic exposure control (AEC) conditions the signal (SIG) measure is proportional to subject contrast; and (3) under AEC conditions the noise (NOI) measure is proportional to the square root of the average absorbed photon energy. Correspondence with basic imaging physics principles shows that the measures are significantly free of artifacts. Precision of the CAMPI measures exceeds that of human observers by orders of magnitude. CAMPI measures are expected to be more relevant to clinical mammography than Fourier metrics as the measurements are done on objects of arbitrary shape and size that were designed by the manufacturer to resemble various detection tasks in mammography. It is concluded that CAMPI can perform objective and highly precise evaluations of phantom image quality in mammography. It could be used as a sophisticated quality control tool, as a replacement for the current ACR/MQSA phantom evaluation program, and to evaluate the rapidly evolving digital mammography technology.
Effects of changes in stopping‐power ratios with field size on electron beam relative output factors
Authors: Zhang G. G. , Rogers D. W. O. , Cygler J. E. , Mackie T. R.
Published: July 2002

Stopping‐power ratios are a function of field size and vary with accelerators. To investigate how these variations affect relative output factor measurements made using ion chambers for electron beams, especially for small fields,is calculated using the Monte Carlo technique for different field sizes, beam energies, and accelerators and is compared to the data in TG‐21 or TG‐25, which are for mono‐energetic broad beams. For very small field sizes defined by cutouts, if the change inwithis ignored (i.e., TG‐25 is not carefully followed), there is an overestimate of relative output factors by up to 3%. Ignoring the field‐size effect on stopping‐power ratio adds an additional overestimate of up to one‐half percent, and using mono‐energetic stopping‐power ratio data instead of realistic beam data gives another error, but in the opposite direction, of up to 0.7%. Due to the cancellation of these latter two errors, following TG‐25 withdata for broad mono‐energetic beams will give the correct answer for the ROF measurement within 0.4% compared to usingdata for which the field‐size effect is considered for realistic electron beams.
The regional Monte Carlo method: A dose calculation method based on accuracy requirement
Authors: Woo M. K. , Scora D. J. , Wong E.
Published: July 2002

In this work we propose the regional Monte Carlo (RMC) method of dose calculation. This method combines the Monte Carlo (MC) algorithm and a non‐MC algorithm (such as the convolution method) for optimal speed and accuracy in dose calculation for both photon and electron beams and for various irradiation and patient geometries. For specific regions in the geometry where high accuracy is required but difficult to obtain with analytical or empirical calculations, such as critical organs surrounded by complicated inhomogeneities, the MC algorithm is used. For regions with simple geometries, or where a high degree of dose accuracy is not critical, the non‐MC algorithm is used to increase speed. There are two aspects of the RMC method. The first one involves determining critical regions and boundaries, and the other involves the actual implementation and mixing of the two computational algorithms. Two examples of different geometries are used to illustrate the different ways to apply the RMC method. The possibility to extend the method to more complicated geometries and inhomogeneities, as well as the ability of the method to incorporate different calculation algorithms, are also discussed.
Peak scatter factors for high energy photon beams
Authors: Li X. Allen
Published: July 2002

The peak scatter factor (PSF) for a photon beam is defined as the ratio of the total dose and the primary dose at the depth of dose maximum. The values of the PSF for photon beams ranging fromto 24 MV are calculated using the EGS4 Monte Carlo technique, to avoid measurement difficulties. The calculation shows that the effect of SSD on PSF for high energy photon beams is not significant for small fields, but can be as high as 1% for large fields. For thebeam, the calculation agrees with the data tabulated on BJR Supplement 25 to within 0.8%. The BJR value (1.054) offoris 0.6% lower than the present value due to the underestimation of scatters from the source capsule and collimators. For a given field size, PSF is varied by up to 2% when beam quality changes fromto 24 MV. For normalized PSF, the values of BJR Supplement 25 (which are assumed to be the same for beams ranging fromto 50 MV) agree well with the present calculation for small field sizes, but are higher than our data by up to 2% for large field sizes. The presently calculated PSFs are related to field size(s) by an empirical expression,wheremandnare the fitting parameters. This equation describes the PSFs within 0.4% (0.15% on average).
Dose enhancement by a thin foil of high‐Zmaterial: A Monte Carlo study
Authors: Li X. Allen , Chu James C. H. , Chen Weimin , Zusag Thomas
Published: July 2002

The purpose of this work is to study the dose enhancement by a thin foil (thickness of 0.2–4 mm) of high‐Zmaterial in a water phantom, irradiated by high‐energy photon beams. EGS4 Monte Carlo technique was used. Perturbations on the beam spectra due to the presence of the foils, and dose enhancement dependence of photon‐beam quality, beam incident angle, atomic number (Z), the thickness and size of the foil, and the depth of the foil situated in the phantom were studied. Analysis of photon and secondary‐electron spectra indicates that the dose enhancement near an inhomogeneity interface is primarily due to secondary electrons. A calculation for 1‐mm‐thick planar lead foil in a water phantom shows that the dose enhancements at 0.25, 1, 2 and 3 mm away from the foil in the backward region were 58%, 37%, 24% and 17%, respectively, for a 15 MV beam. Calculations for a variety of planar foils and photon beams show that dose enhancement: (a) increases withZ; (b) decreases with decreasing foil thickness when the foils are thinner than a certain value (1 mm for lead foil for 15 MV); (c) decreases with decreasing incident photon‐beam energies; (d) changes slightly for beam incident angles less than 45° and more prominently for larger angles; (e) increases with size of foil; and (f) is almost independent of the depth at which the foil is situated when the foil is placed beyond the range of secondary electrons. The dose enhancement calculation is also performed for a cylindrically shaped lead foil irradiated by a four‐field‐box. The dose enhancement of 34%/13% was obtained at 0.25/2 mm away from the cylindrical outer interface for a 15 MV four‐field‐box.
A practical technique for verification of three‐dimensional conformal dose distributions in stereotactic radiosurgery
Authors: Robar J. L. , Clark B. G.
Published: July 2002

The trend toward conformal techniques in stereotactic radiosurgery necessitates an accurate and practical method for verification of irregular three‐dimensional dose distributions. This work presents the design and evaluation of a phantom system facilitating the measurement of conformal dose distributions using one or more arrays of up to 20 radiographic films separated by 3.2 mm‐thick tissue‐equivalent spacers. Using Electron Gamma Shower version 4 (EGS4) Monte Carlo simulation, we show that for 6 MV radiosurgical photon beams this arrangement preserves tissue‐equivalence to within 1%. The phantom provides 0.25 mm in‐plane spatial resolution and multiple sets of films may be used to resample the dose volume in orthogonal planes. Dedicated software has been developed to automate the process of ordering and orienting of scanned film images, conversion of scanned pixel value to dose, resampling of one or more sets of film images and subsequent export of images in DICOM format for coregistration of planned and measured dose volumes. Calculated and measured isodose surfaces for a simple, circular‐beam treatment agree to within 1.5 mm throughout the dose volume. For conformal radiosurgical applications, the measured and planned dose distributions agree to within the uncertainty of the manufacture of irregularly shaped collimators. The sensitivity of this technique to minor spatial inaccuracies in beam shaping is also demonstrated.
A course in computer-based data acquisition
Authors: Hubin W. N.
Published: July 2002

The evolution of a course in computer-based data acquisition and analysis is described. The physics of the sensors, the physics of the system under study, and practical electrical measurement techniques are emphasized in this course, as well as computer hardware and software. Three experiments of particular physical interest are described in detail: heat flow in a metal plate, light-emitting diode characteristics, and the sounds generated by a speech chip.