bluuebunny/crossref_metadata_2025 huggingface dataset:
Deficiencies of Human Complement Component C4a and C4b and Heterozygosity in Length Variants ofRP-C4-CYP21-TNX(Rccx) Modules in Caucasians
Authors: Blanchong Carol A. , Zhou Bi , Rupert Kristi L. , Chung Erwin K. , Jones Karla N. , Sotos Juan F. , Zipf William B. , Rennebohm Robert M. , Yu C. Yung
Published: July 2002

The complement component C4 genes located in the major histocompatibility complex (MHC) class III region exhibit an unusually complex pattern of variations in gene number, gene size, and nucleotide polymorphism. Duplication or deletion of a C4 gene always concurs with its neighboring genes serine/threonine nuclear protein kinase RP, steroid 21-hydroxylase (CYP21), and tenascin (TNX), which together form a genetic unit termed the RCCX module. A detailed molecular genetic analysis of C4A and C4B and RCCX modular arrangements was correlated with immunochemical studies of C4A and C4B protein polymorphism in 150 normal Caucasians. The results show that bimodular RCCX has a frequency of 69%, whereas monomodular and trimodular RCCX structures account for 17.0 and 14.0%, respectively. Three quarters of C4 genes harbor the endogenous retrovirus HERV-K(C4). Partial deficiencies of C4A and C4B, primarily due to gene deletions and homoexpression of C4A proteins, have a combined frequency of 31.6%. This is probably the most common variation of gene dosage and gene size in human genomes. The seven RCCX physical variants create a great repertoire of haplotypes and diploid combinations, and a heterozygosity frequency of 69.4%. This phenomenon promotes the exchange of genetic information among RCCX constituents that is important in homogenizing the structural and functional diversities of C4A and C4B proteins. However, such length variants may cause unequal, interchromosomal crossovers leading to MHC-associated diseases. An analyses of the RCCX structures in 22 salt-losing, congenital adrenal hyperplasia patients revealed a significant increase in the monomodular structure with a long C4 gene linked to the pseudogene CYP21A, and bimodular structures with two CYP21A, which are likely generated by recombinations between heterozygous RCCX length variants.
The Semiconserved Head Structure of Plasmodium falciparum Erythrocyte Membrane Protein 1 Mediates Binding to Multiple Independent Host Receptors
Authors: Chen Qijun , Heddini Andreas , Barragan Antonio , Fernandez Victor , Pearce S. Frieda A. , Wahlgren Mats
Published: July 2002

Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature. Blockage of the blood flow, hampered oxygen delivery, and severe malaria may follow if binding is excessive. The NH2-terminal head structure (Duffy binding–like domain 1 [DBL1α]–cysteine-rich interdomain region [CIDR1α]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate–like glucosaminoglycan, and CD36. DBL2δ was found to mediate additional binding to PECAM-1/CD31. The exceptional binding activity of the PfEMP1 head structure and its relatively conserved nature argues that it holds an important role in erythrocyte sequestration and therefore in the virulence of the malaria parasite.
Inactivation and Secondary Structure in the D4/S4-5 Region of the SkM1 Sodium Channel
Authors: Filatov Gregory N. , Nguyen Thao P. , Kraner Susan D. , Barchi Robert L.
Published: July 2002

The D4/S4-5 interhelical region plays a role in sodium channel fast inactivation. Examination of S4-5 primary structure in all domains suggests a possible amphipathic helical conformation in which a conserved group of small hydrophobic residues occupies one contiguous surface with a more variable complement of nonpolar and polar residues on the opposite face. We evaluated this potential structure by replacing each residue in D4/S4-5 of the rat SkM1 skeletal muscle sodium channel with substitutions having different side chain properties. Of the 63 mutations analyzed, 44 produced functional channels. P1473 was intolerant of substitutions. Nonpolar substitutions in the conserved hydrophobic region were functionally similar to wild type, while charged mutations in this region before P1473 were nonfunctional. Charged mutations at F1466, M1469, M1470, and A1474, located on the opposite surface of the predicted helix, produced functional channels with pronounced slowing of inactivation, shifted voltage dependence of steady-state inactivation, and increased rate of recovery from inactivation. The substituted-cysteine-accessibility method was used to probe accessibility at each position. Residues L1465, F1466, A1467, M1469, M1470, L1472, A1474, and F1476C were easily accessible for modification by sulfhydryl reagents; L1464, L1468, S1471, and L1475 were not accessible within the time frame of our measurements. Molecular dynamics simulations of residues A1458 to N1477 were then used to explore energetically favorable local structures. Based on mutagenesis, substituted-cysteine-accessibility method, and modeling results, we suggest a secondary structure for the D4/S4-5 region in which the peptide chain is α-helical proximal to P1473, bends at this residue, and may continue beyond this point as a random coil. In this configuration, the entire resultant loop is amphipathic; four residues on one surface could form part of the binding site for the inactivation particle.
In Intact Cone Photoreceptors, a Ca2+-dependent, Diffusible Factor Modulates the cGMP-gated Ion Channels Differently than in Rods
Authors: Rebrik Tatiana I. , Korenbrot Juan I.
Published: July 2002

We investigated the modulation of cGMP-gated ion channels in single cone photoreceptors isolated from a fish retina. A new method allowed us to record currents from an intact outer segment while controlling its cytoplasmic composition by superfusion of the electropermeabilized inner segment. The sensitivity of the channels to agonists in the intact outer segment differs from that measured in membrane patches detached from the same cell. This sensitivity, measured as the ligand concentration necessary to activate half-maximal currents, K1/2, also increases as Ca2+ concentration decreases. In electropermeabilized cones, K1/2 for cGMP is 335.5 ± 64.4 μM in the presence of 20 μM Ca2+, and 84.3 ± 12.6 μM in its absence. For 8Br-cGMP, K1/2 is 72.7 ± 11.3 μM in the presence of 20 μM Ca2+ and 15.3 ± 4.5 μM in its absence. The Ca2+-dependent change in agonist sensitivity is larger in extent than that measured in rods. In electropermeabilized tiger salamander rods, K1/2 for 8Br-cGMP is 17.9 ± 3.8 μM in the presence of 20 μM Ca2+ and 7.2 ± 1.2 μM in its absence. The Ca2+-dependent modulation is reversible in intact cone outer segments, but is progressively lost in the absence of divalent cations, suggesting that it is mediated by a diffusible factor. Comparison of data in intact cells and detached membrane fragments from cones indicates that this factor is not calmodulin. At 40 μM 8Br-cGMP, the Ca2+-dependent change in sensitivity in cones is half-maximal at KCa = 286 ± 66 nM Ca2+. In rods, by contrast, KCa is ∼50 nM Ca2+. The difference in magnitude and Ca2+ dependence of channel modulation between photoreceptor types suggests that this modulation may play a more significant role in the regulation of photocurrent gain in cones than in rods.
Single-Channel Properties of Recombinant Acid-Sensitive Ion Channels Formed by the Subunits Asic2 and Asic3 from Dorsal Root Ganglion Neurons Expressed in Xenopus Oocytes
Authors: Zhang Ping , Canessa Cecilia M.
Published: July 2002

The acid-sensitive ion channels known as ASIC are gated by external protons. A set of these channels is expressed in dorsal root ganglion neurons where they may participate in the transduction of mechanical and nociceptive stimuli. Here, we have examined the single-channel properties of channels formed by the subunits ASIC2 and ASIC3 expressed in Xenopus oocytes using outside-out patches. The mean single-channel current-voltage relationship is linear with a slope conductance of 18 pS between −80 and −40 mV in 150 mM Na+ outside and 150 mM K+ inside the patch pipet. The selectivity for monovalent cations has the sequence Na+ > Li+ > K+. Divalent cations such as Ca2+ do not permeate, but instead block the channel when applied to the extracellular side. External protons increase the probability of channels being open to a maximum of 0.8 with an EC50 of 16 ± 4 μM and a Hill coefficient of 2.7 ± 0.3, whereas the mean single-channel current amplitude is independent of external pH. Analysis of the kinetics of single channels indicates the presence of at least four modes of activity (Mod1 to Mod4) in addition to an inactivated state. Three of the modes exhibit distinct kinetics, and can be unambiguously identified on the basis of open probability (PoMod1 = 0.5 ± 0.05; PoMod2 > 0.9 ± 0.05; PoMod3 < 0.1). Mode 4, which has a Po in the range of 0.5–0.8, may constitute a distinct mode or alternatively, it represents transitions between the other three modes of activity. Increasing [H+]o increases the frequency of entering the modes with high Po (modes 1, 2, and 4) and the time the channel spends in the modes with high activity.
Efficient Coupling of Ligand Binding to Channel Opening by the Binding Domain of a Modulatory (β) Subunit of the Olfactory Cyclic Nucleotide-Gated Channel
Authors: Young Edgar C. , Sciubba Daniel M. , Siegelbaum Steven A.
Published: July 2002

CNG channels in vivo are heteromers of homologous α and β subunits that each contain a six-transmembrane segment domain and a COOH-terminal cytoplasmic cyclic nucleotide binding domain (BD). In heterologous expression systems, heteromeric αβ channels activate with greater sensitivity to ligand than do homomeric α channels; however, ligand-gating of channels containing only β subunit BDs has never been studied because β subunits cannot form functional homomeric CNG channels. To characterize directly the contribution of the β subunit BD to ligand-gating, we constructed a chimeric subunit, X-β, whose BD sequence was that of the β subunit CNG5 from rat, but whose sequence outside the BD was derived from α subunits. For comparison, we constructed another chimera, X-α, whose sequence outside the BD was identical to that of X-β, but whose BD sequence was that of the α subunit CNG2 from catfish. When expressed in Xenopus oocytes, X-β and X-α each formed functional homomeric channels activated by both cAMP and cGMP. This is the first demonstration that the β subunit BD can couple ligand binding to activation in the absence of α subunit BD residues. Notably, both agonists activate X-β more effectively than X-α (higher opening efficacy and lower K1/2). The BD is believed to comprise two functionally distinct subdomains: (1) the roll subdomain (β-roll and flanking A- and B-helices) and (2) the C-helix subdomain. Opening efficacy was previously believed to be controlled primarily by the C-helix, but when we made additional chimeras by exchanging the subdomains between X-β and X-α, we found that both subdomains contain significant determinants of efficacy and agonist selectivity. In particular, only channels containing the roll subdomain of the β subunit had high efficacy. Thermodynamic linkage analysis shows that interaction between the two subdomains accounts for a significant portion of their contribution to activation energetics.
HEK293S Cells Have Functional Retinoid Processing Machinery
Authors: Brueggemann Lioubov I. , Sullivan Jack M.
Published: July 2002

Rhodopsin activation is measured by the early receptor current (ERC), a conformation-associated charge motion, in human embryonic kidney cells (HEK293S) expressing opsins. After rhodopsin bleaching in cells loaded with 11-cis-retinal, ERC signals recover in minutes and recurrently over a period of hours by simple dark adaptation, with no added chromophore. The purpose of this study is to investigate the source of ERC signal recovery in these cells. Giant HEK293S cells expressing normal wild-type (WT)-human rod opsin (HEK293S) were regenerated by solubilized 11-cis-retinal, all-trans-retinal, or Vitamin A in darkness. ERCs were elicited by flash photolysis and measured by whole-cell recording. Visible flashes initially elicit bimodal (R1, R2) ERC signals in WT-HEK293S cells loaded with 11-cis-retinal for 40 min or overnight. In contrast, cells regenerated for 40 min with all-trans-retinal or Vitamin A had negative ERCs (R1-like) or none at all. After these were placed in the dark overnight, ERCs with outward R2 signals were recorded the following day. This indicates conversion of loaded Vitamin A or all-trans-retinal into cis-retinaldehyde that regenerated ground-state pigment. 4-butylaniline, an inhibitor of the mammalian retinoid cycle, reversibly suppressed recovery of the outward R2 component from Vitamin A and 11-cis-retinal–loaded cells. These physiological findings are evidence for the presence of intrinsic retinoid processing machinery in WT-HEK293S cells similar to what occurs in the mammalian eye.
Setting up a first website for society publications
Authors: McKinty K. , Saadat S. , Smith F. J. , Donovan B. T.
Published: July 2002

A co‐operative project between the Association of Learned and Professional Society Publishers and Queen's University, Belfast, supported by the Electronic Libraries Programme, was set up to create a website and host the publications of five learned societies on an experimental basis. In the light of the experience gained, societies who have not taken the first steps in providing electronic services for their members and subscribers are offered advice on the structure, setup, and service requirements for their first website.
What can technology offer? Notes on technical developments for the non‐technical
Authors: Brown Iain D.
Published: July 2002

The internet is assuming an all‐pervasive presence on television, radio, telephones and in the papers. Yet in what ways can value be added to existing content? What does the internet really offer in terms of technology and content management? It is suggested that publishers can use the internet to their advantage through the repurposing of content.
The market for university press books in the United States: 1985–1999
Authors: Greco Albert N.
Published: July 2002

University press books play a pivotal role in the transmission of knowledge among academics and to serious readers outside universities. Yet the market for these books underwent substantive changes and posted lacklustre increases in net publishers' revenues and unit sales between 1985 and 1999. In this article, statistical data on university presses' net publishers' unit and dollar revenues, covering the years 1985 through 1999, are analysed to ascertain: (i) shifts in the channels of distribution; (ii) the future demand for university press books for the years 2000 through 2004; and (iii) the price elasticity of demand for these titles. Other issues addressed briefly include competition from commercial academic publishers, consolidation in the publishing industry, the rise in importance of the global market for university press books, and financial issues.
The useful archive
Authors: Anderson Kent
Published: July 2002

Archives have historically been remote and inaccessible, but the Internet wrests the archive from a passive role for custodians into an active role for publishers and readers. This paper examines the implications of a networked archive on archiving, reading, publishing, and access.
Print to electronic: measuring the operational and economic implications of an electronic journal collection
Authors: Montgomery Carol Hansen
Published: July 2002

This paper reports the methodology and initial results of an Institute for Library and Information Studies (IMLS)‐funded research study of the operational and economic impact of an academic library's migration to an all‐electronic journal collection. Initial results of measuring staff time indicate Information Services and Systems Operation departments constitute the majority of personnel costs for electronic journals. Technical Services and Circulation account for the majority of staff costs for print journals. Per title subscription costs appear to be substantially lower for electronic titles obtained through aggregator collections.
Getting it! The added value of helping users find information
Authors: Kaser Richard T.
Published: July 2002

This paper focuses on the evolving role of secondary publishers within the changing models of web‐assisted information provision. It concludes that the predicted demise of secondary publishing was premature. Instead, everybody is now delivering a service, not just a product and, despite the rhetoric of freeing the literature, even commercial web enterprises are moving towards the subscription model.
Book reviews
Authors: Storrie Eileen , Bell Hazel K.
Published: July 2002

The Peer‐Reviewed Journal: A Comprehensive Guide through the Editorial Process by Gary Michael Smith, Chatgris Press New Orleans, USA, 80 pp & 63 pp of Figs., $35.00, ISBN 0‐9658380‐0‐5

The Book in the United States Today edited by Richard Abel and Gordon Graham, Transaction Publishers, 1997., ix, 280 pages., Index., ISBN: 1‐56000‐972‐1 (pbk), $21.95 / £14.95.
Indexing the continuum of verbal texts
Authors: Wellisch Hans H.
Published: July 2002

Differentiates items on a continuum of verbal texts as: books (single‐author, small‐team, multiple‐author, encyclopedias); periodicals (journals, bulletins, bibliographic volume indexes, cumulations); databases. The requirements of their indexing, with varying problems of policy, language, depth, authors' names, and titles, in both printed and electronic form, are discussed.
Riding the iceberg: exploiting the Internet to promote one's organisation
Authors: Dixon Anne
Published: July 2002

An analysis of the electronic marketing options available to publishers, including Institute of Physics Publishing's experience of the effectiveness of some of those options. Particular emphasis is placed on Usenet and E‐Mail and what is deemed to be acceptable and unacceptable practice.
On the constructible numbers
Authors: Videla Carlos
Published: July 2002

Let

Ω
\Omega

be the field of constructible numbers, i.e. the numbers constructed from a given unit length using ruler and compass. We prove

Z

~

∩
Ω

\widetilde {\mathbb Z}\cap \Omega

is definable in

Ω
\Omega

.
Polynomial invariants of finite groups. A survey of recent developments
Authors: Smith Larry
Published: July 2002

The polynomial invariants of finite groups have been studied for more than a century now and continue to find new applications and generate interesting problems. In this article we will survey some of the recent developments coming primarily from algebraic topology and the rediscovery of old open problems.
Bochner-Kähler metrics
Authors: Bryant Robert
Published: July 2002

A Kähler metric is said to be Bochner-Kähler if its Bochner curvature vanishes. This is a nontrivial condition when the complex dimension of the underlying manifold is at least 

2
2

. In this article it will be shown that, in a certain well-defined sense, the space of Bochner-Kähler metrics in complex dimension 

n
n

has real dimension

n

+

1

n{+}1

and a recipe for an explicit formula for any Bochner-Kähler metric will be given. It is shown that any Bochner-Kähler metric in complex dimension 

n
n

has local (real) cohomogeneity at most 

n
n

. The Bochner-Kähler metrics that can be ‘analytically continued’ to a complete metric, free of singularities, are identified. In particular, it is shown that the only compact Bochner-Kähler manifolds are the discrete quotients of the known symmetric examples. However, there are compact Bochner-Kähler orbifolds that are not locally symmetric. In fact, every weighted projective space carries a Bochner-Kähler metric. The fundamental technique is to construct a canonical infinitesimal torus action on a Bochner-Kähler metric whose associated momentum mapping has the orbits of its symmetry pseudo-groupoid as fibers.
The effect of evenly spaced constant sites on the distribution of the random division of a molecular sequence.
Authors: Sneath P H
Published: July 2002

MOTIVATION: A modified Sherman statistic can be used to test whether the differences between two aligned sequences are distributed at random along the sequences, or whether they are clustered, which suggests anomalies of evolution such as partial gene recombination or functional constraints. The presence of evenly spaced constant sites (such as constancy at the second codon position in genes coding for proteins) lowers the statistic and makes the significance less than it should be. RESULTS: The magnitude of the constant-site effect is shown by simulation to depend mainly on the proportion of differences between two sequences and on the number of constant sites that are added after each variable site. This latter number can be estimated from the variance of sites in a sequence matrix at the first, second and third codon positions, to obtain a ratio that corrects the statistic. When expressed as standard errors, the uncorrected results are too low (typically half to one unit when almost all the variation is at the third codon position). Correction raises the standard errors to levels close to expectation. If the data show no marked ternary periodicity, the correction is very small. The method is illustrated with biological data that show close to random behaviour, and with data that exhibit strong clustering. AVAILABILITY: The software is available from the author and has also been placed on the EMBL file server (Software@embl-ebi.ac.uk). CONTACT: phas1@le.ac.uk
A platform for integrating threading results with protein
family analyses
Authors: Pazos Florencio , Rost Burkhard , Valencia Alfonso
Published: July 2002

Summary: We have developed a package for the interactive visualization of results from different threading programs. Additionally, we have integrated relevant information about protein sequence, function, evolution, and structure into the interface.

Availability: A detailed documentation of THREADLIZE, and the binaries for IRIX, SunOS and Linux are available at http://www.cnb.uam.es/~pazos/threadlize. The package is free for academic users.

Contact: valencia@cnb.uam.es

Supplementary information: http://www.cnb.uam.es/~pazos/threadlize
An ontology for bioinformatics applications.
Authors: Baker P G , Goble C A , Bechhofer S , Paton N W , Stevens R , Brass A
Published: July 2002

MOTIVATION: An ontology of biological terminology provides a model of biological concepts that can be used to form a semantic framework for many data storage, retrieval and analysis tasks. Such a semantic framework could be used to underpin a range of important bioinformatics tasks, such as the querying of heterogeneous bioinformatics sources or the systematic annotation of experimental results. RESULTS: This paper provides an overview of an ontology [the Transparent Access to Multiple Biological Information Sources (TAMBIS) ontology or TaO] that describes a wide range of bioinformatics concepts. The present paper describes the mechanisms used for delivering the ontology and discusses the ontology's design and organization, which are crucial for maintaining the coherence of a large collection of concepts and their relationships. AVAILABILITY: The TAMBIS system, which uses a subset of the TaO described here, is accessible over the Web via http://img.cs.man.ac.uk/tambis (although in the first instance, we will use a password mechanism to limit the load on our server). The complete model is also available on the Web at the above URL.
BRCA1 can stimulate gene transcription by a unique mechanism
Authors: Nadeau Guy , Boufaied Nadia , Moisan Annie , Lemieux Karine M , Cayanan Charmagne , Monteiro Alvaro N A , Gaudreau Luc
Published: July 2002

Most familial breast and ovarian cancers have been linked to mutations in the BRCA1 gene. BRCA1 has been shown to affect gene transcription but how it does so remains elusive. Here we show that BRCA1 can stimulate transcription without the requirement for a DNA‐tethering function in mammalian and yeast cells. Furthermore, the BRCA1 C‐terminal region can stimulate transcription of the p53‐responsive promoter, MDM2. Unlike many enhancer‐specific activators, non‐tethered BRCA1 does not require a functional TATA element to stimulate transcription. Our results suggest that BRCA1 can enhance transcription by a function additional to recruiting the transcriptional machinery to a targeted gene.
A hybrid bacterial replication origin
Authors: Seitz Harald , Welzeck Michaela , Messer Walter
Published: July 2002

We constructed a hybrid replication origin that consists of the main part of oriC from Escherichia coli, the DnaA box region and the AT‐rich region from Bacillus subtilis oriC. The AT‐rich region could be unwound by E. coli DnaA protein, and the DnaB helicase was loaded into the single‐stranded bubble. The results show that species specificity, i.e. which DnaA protein can do the unwinding, resides within the DnaA box region of oriC.
GyrI: a counter‐defensive strategy against proteinaceous inhibitors of DNA gyrase
Authors: Chatterji Monalisa , Nagaraja Valakunja
Published: July 2002

DNA gyrase is the target of two plasmid‐encoded toxins CcdB and microcin B17, which ensure plasmid maintenance. These proteins stabilize gyrase–DNA covalent complexes leading to double‐strand breaks in the genome. In contrast, the physiological role of chromosomally encoded inhibitor of DNA gyrase (GyrI) in Escherichia coli is unclear and its mechanism of inhibition has not been established. We demonstrate that the mode of inhibition of GyrI is distinct from all other gyrase inhibitors. It inhibits DNA gyrase prior to, or at the step of, binding of DNA by the enzyme. GyrI reduces intrinsic as well as toxin‐stabilized gyrase–DNA covalent complexes. Furthermore, GyrI reduces microcin B17‐mediated double‐strand breaks in vivo, imparting protection to the cells against the toxin, substantiating the in vitro results. Thus, GyrI is an antidote to DNA gyrase‐specific proteinaceous poisons encoded by plasmid addiction systems.
Distribution and putative function of autonomic nerve fibres in the bill skin of the platypus (Ornithorhynchus anatinus)
Authors: Manger Paul R. , Keast Janet R. , Pettigrew John D. , Troutt Louise
Published: July 2002

The electroreceptors located in the bill skin of the platypus are modified secretory glands. The electroreceptive nerve terminals form bare endings in close proximity to the duct of these glands. In this study, we describe the autonomic innervation of the glands and a separate specialized autonomic innervation of the epidermal portion of the glandular duct. A range of immunohistochemical labels showed that the gland cells of the electroreceptors have a non–noradrenergic (putative parasympathetic) innervation. Phalloidin labelling revealed a ‘phincter’ of epidermal luminal cells that labelled strongly for actin. These actin–dense keratinocytes were seen to have a noradrenergic (putative sympathetic) innervation. Fine–diameter sensory fibres containing substance P (presumably C–fibre thermoreceptors or polymodal nociceptors) were observed to terminate in the superficial epidermis surrounding the pore of the gland. When the bill of the platypus is dry these pores were closed. However, when room temperature water was washed over the bill, the pores opened. It is proposed that this autonomic and sensory innervation, along with the actin sphincter, mediates the opening and closing of the pores. By doing this, the platypus prevents the desiccation of the bare electrosensory nerve terminals when it is out of the water, and it may also be a way to regulate the impedance of the internal electrical circuit presented to the water at the pores.
Haltere–mediated equilibrium reflexes of the fruit fly, Drosophila melanogaster
Authors: Dickinson Michael H.
Published: July 2002

Flies display a sophisticated suite of aerial behaviours that require rapid sensory–motor processing. Like all insects, flight control in flies is mediated in part by motion–sensitive visual interneurons that project to steering motor circuitry within the thorax. Flies, however, possess a unique flight control equilibrium sense that is encoded by mechanoreceptors at the base of the halteres, small dumb–bell–shaped organs derived through evolutionary transformation of the hind wings. To study the input of the haltere system onto the flight control system, I constructed a mechanically oscillating flight arena consisting of a cylindrical array of light–emitting diodes that generated the moving image of a 30° vertical stripe. The arena provided closed–loop visual feedback to elicit fixation behaviour, an orientation response in which flies maintain the position of the stripe in the front portion of their visual field by actively adjusting their wing kinematics. While flies orientate towards the stripe, the entire arena was swung back and forth while an optoelectronic device recorded the compensatory changes in wing stroke amplitude and frequency. In order to reduce the background changes in stroke kinematics resulting from the animal's closed–loop visual fixation behaviour, the responses to eight identical mechanical rotations were averaged in each trial. The results indicate that flies possess a robust equilibrium reflex in which angular rotations of the body elicit compensatory changes in both the amplitude and stroke frequency of the wings. The results of uni– and bilateral ablation experiments demonstrate that the halteres are required for these stability reflexes. The results also confirm that halteres encode angular velocity of the body by detecting the Coriolis forces that result from the linear motion of the haltere within the rotating frame of reference of the fly's thorax. By rotating the flight arena at different orientations, it was possible to construct a complete directional tuning map of the haltere–mediated reflexes. The directional tuning of the reflex is quite linear such that the kinematic responses vary as simple trigonometric functions of stimulus orientation. The reflexes function primarily to stabilize pitch and yaw within the horizontal plane.
Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease
Authors: Cha Jang-Ho J. , Frey Ariel S. , Alsdorf Stephen A. , Kerner Julie A. , Kosinski Christoph M. , Mangiarini Laura , Penney John B. , Davies Stephen W. , Bates Gillian P. , Young Anne B.
Published: July 2002

Alterations in neurotransmitter receptors are a pathological hallmark of the neurodegeneration seen in Huntington's disease (HD). However, the significance of these alterations has been uncertain, possibly reflecting simply the loss of brain cells. It is not known for certain whether the alteration of neurotransmitter receptors occurs before the onset of symptoms in human HD. Recently we developed transgenic mice that contain a portion of a human
HD
gene and develop a progressive abnormal neurological phenotype. Neurotransmitter receptors that are altered in HD (receptors for glutamate, dopamine, acetylcholine and adenosine) are decreased in the brain of transgenic mice, in some cases before the onset of behavioural or motor symptoms. In transgenic mice, neurotransmitter receptor alterations occur before neuronal death. Further, receptor alterations are selective in that certain receptors, namely
N
-methyl-D-aspartate and γ-aminobutyric acid receptors, are unaltered. Finally, receptor decreases are preceded by selective decreases in the corresponding mRNA species, suggesting the altered transcription of specific genes. These results suggest that (i) receptor decreases precede, and therefore might contribute to, the development of clinical symptoms, and (ii) altered transcription of specific genes might be a key pathological mechanism in HD.
Do oxidative stress conditions impairing photosynthesis in the light manifest as photoinhibition?
Authors: Hideg Éva , Tamás Kálai , Hideg Kálmán , Vass Imre
Published: July 2002

We compared the effect of photoinhibition by excess photosynthetically active radiation (PAR), UV–B irradiation combined with PAR, low temperature stress and paraquat treatment on photosystem (PS) II. Although the experimental conditions ensured that the four studied stress conditions resulted in approximately the same extent of PS II inactivation, they clearly followed different molecular mechanisms. Our results show that singlet oxygen production in inactivated PS II reaction centres is a unique characteristic of photoinhibition by excess PAR. Neither the accumulation of inactive PS II reaction centres (as in UV–B or chilling stress), nor photo–oxidative damage of PS II (as in paraquat stress) is able to produce the special oxidizing conditions characteristic of acceptor–side–induced photoinhibition.
Gibberellin regulates Arabidopsis seed germination via RGL2, a GAI/RGA-like gene whose expression is up-regulated following imbibition
Authors: Lee Sorcheng , Cheng Hui , King Kathryn E. , Wang Weefuen , He Yawen , Hussain Alamgir , Lo Jane , Harberd Nicholas P. , Peng Jinrong
Published: July 2002

The germination of Arabidopsis seeds is promoted by gibberellin (GA). Arabidopsis GAI, and RGA are genes encoding key GA signal-transduction components (GAI and RGA) that mediate GA regulation of stem elongation. The Arabidopsisgenome contains two further genes, RGL1 and RGL2, that encode proteins (RGL1 and RGL2) that are closely related to GAI and RGA. Here, we show that RGL2 regulates seed germination in response to GA, and that RGL1, GAI, and RGA do not. In addition, we show thatRGL2 transcript levels rise rapidly following seed imbibition, and then decline rapidly as germination proceeds. In situ GUS staining revealed that RGL2 expression in imbibed seeds is restricted to elongating regions of pre-emergent and recently emerged radicles. These observations indicate that RGL2 is a negative regulator of GA responses that acts specifically to control seed germination rather than stem elongation. Furthermore, as RGL2 expression is imbibition inducible, RGL2 may function as an integrator of environmental and endogenous cues to control seed germination.
The role of aromatic residues in the hydrophobic core of the villin headpiece subdomain
Authors: Frank Benjamin S. , Vardar Didem , Buckley Deirdre A. , McKnight C. James
Published: July 2002

Small autonomously folding proteins are of interest as model systems to study protein folding, as the same molecule can be used for both experimental and computational approaches. The question remains as to how well these minimized peptide model systems represent larger native proteins. For example, is the core of a minimized protein tolerant to mutation like larger proteins are? Also, do minimized proteins use special strategies for specifying and stabilizing their folded structure? Here we examine these questions in the 35‐residue autonomously folding villin headpiece subdomain (VHP subdomain). Specifically, we focus on a cluster of three conserved phenylalanine (F) residues F47, F51, and F58, that form most of the hydrophobic core. These three residues are oriented such that they may provide stabilizing aromatic–aromatic interactions that could be critical for specifying the fold. Circular dichroism and 1D‐NMR spectroscopy show that point mutations that individually replace any of these three residues with leucine were destabilized, but retained the native VHP subdomain fold. In pair‐wise replacements, the double mutant that retains F58 can adopt the native fold, while the two double mutants that lack F58 cannot. The folding of the double mutant that retains F58 demonstrates that aromatic–aromatic interactions within the aromatic cluster are not essential for specifying the VHP subdomain fold. The ability of the VHP subdomain to tolerate mutations within its hydrophobic core indicates that the information specifying the three dimensional structure is distributed throughout the sequence, as observed in larger proteins. Thus, the VHP subdomain is a legitimate model for larger, native proteins.
Simple beam models for Monte Carlo photon beam dose calculations in radiotherapy
Authors: Fix Michael K. , Keller Harald , Rüegsegger Peter , Born Ernst J.
Published: July 2002

Monte Carlo (code GEANT) produced 6 and 15 MV phase space (PS) data were used to define several simple photon beam models. For creating the PS data the energy of starting electrons hitting the target was tuned to get correct depth dose data compared to measurements. The modeling process used the full PS information within the geometrical boundaries of the beam including all scattered radiation of the accelerator head. Scattered radiation outside the boundaries was neglected. Photons and electrons were assumed to be radiated from point sources. Four different models were investigated which involved different ways to determine the energies and locations of beam particles in the output plane. Depth dose curves, profiles, and relative output factors were calculated with these models for six field sizes from to and compared to measurements. Model 1 uses a photon energy spectrum independent of location in the PS plane and a constant photon fluence in this plane. Model 2 takes into account the spatial particle fluence distribution in the PS plane. A constant fluence is used again in model 3, but the photon energy spectrum depends upon the off axis position. Model 4, finally uses the spatial particle fluence distribution and off axis dependent photon energy spectra in the PS plane. Depth dose curves and profiles for field sizes up to were not model sensitive. Good agreement between measured and calculated depth dose curves and profiles for all field sizes was reached for model 4. However, increasing deviations were found for increasing field sizes for models 1–3. Large deviations resulted for the profiles of models 2 and 3. This is due to the fact that these models overestimate and underestimate the energy fluence at large off axis distances. Relative output factors consistent with measurements resulted only for model 4.
Automatic segmentation of breast lesions on ultrasound
Authors: Horsch Karla , Giger Maryellen L. , Venta Luz A. , Vyborny Carl J.
Published: July 2002

In this paper we present a computationally efficient segmentation algorithm for breast masses on sonography that is based on maximizing a utility function over partition margins defined through gray‐value thresholding of a preprocessed image. The performance of the segmentation algorithm is evaluated on a database of 400 cases in two ways. Of the 400 cases, 124 were complex cysts, 182 were benign solid lesions, and 94 were malignant lesions. In the first evaluation, the computer‐delineated margins were compared to manually delineated margins. At an overlap threshold of 0.40, the segmentation algorithm correctly delineated 94% of the lesions. In the second evaluation, the performance of our computer‐aided diagnosis method on the computer‐delineated margins was compared to the performance of our method on the manually delineated margins. Round robin evaluation yielded values of 0.90 and 0.87 on the manually delineated margins and the computer‐delineated margins, respectively, in the task of distinguishing between malignant and nonmalignant lesions.
A correction method for diamond detector signal dependence with proton energy
Authors: Fidanzio A. , Azario L. , De Angelis C. , Pacilio M. , Onori S. , Kacperek A. , Piermattei A.
Published: July 2002

Small dosimeters as solid state detectors can be useful for the dosimetric characterization and periodic quality control of radiotherapy proton beams. The calibration of solid state detectors for proton beams is not a solved problem especially for ophthalmologic proton beams, where these detectors present a LET‐dependent signal. In this work a PTW diamond detector has been selected because of its good signal reproducibility (0.3%) and stable response with accumulated dose. A method that takes into account the LET dependence of the diamond detector signal, at 62 MeV proton beam, is here proposed. In particular an empirical correction factor, has been determined as a function of the residual range quality index, to correct the diamond detector signal for a proton beam of incident effective energy A dedicated software allows us to use the diamond detector as an on‐line reference dosimeter, where an ionization chamber may be difficult to use, or for periodic quality control procedures. The article also reports a comparison between the signal dependence on proton energy of silicon, diamond, and radiochromic film detectors.
Dosimetric perturbations of linear array of β‐emitter seeds and metallic stent in intravascular brachytherapy
Authors: Ye Sung‐Joon , Li X. Allen , Zimmer John R. , Chu James C. , Choi Chan K.
Published: July 2002

The radiation treatment with catheter‐based β‐emitter sources is under clinical trials to prevent restenosis following interventional coronary procedures. There are still large uncertainties in the dose calculation due to the complicated treatment geometry. We present the Monte Carlo simulations to account for the dosimetric perturbations due to neighboring trained seeds, proximal/distal gold markers, and a stainless steel stent. A catheter‐based β‐emitter system is modeled using the Monte Carlo code, MCNP4B. Dose distributions and dose rates are calculated in voxels around the long cylindrical trains of source with and without the stent (at 1.92 mm from the source axis). For the total activity of 70 mCi Bq), the dose around most of the source length (except for edge seeds and gold markers) varies from 40 to 0.23 cGy/s as the radial distance from the source axis increases from 0.64 to 6.4 mm. At the prescription range of the dose gradient is very steep and the contribution of neighboring seeds to the dose is significant. The dose enhancement due to neighboring seeds (the so‐called “train effect”) varies from 9% to 64% as increases from 0.64 to 5.2 mm. The doses at from the last edge seed and the gold marker are about 80% and 40% of that of the nonedge seed (8.7 cGy/s), respectively. The dose enhancement due to the secondary electrons and the primary electrons scattered with the stent is shown to be about 9.3% in the voxel including the stent. However, as increases beyond the stent the dose is slightly reduced by 4%–12%, compared to that without the stent.
Quality management of medical physics issues at the German heavy ion therapy project
Authors: Karger Christian P. , Hartmann Günther H. , Jäkel Oliver , Heeg Peter
Published: July 2002

For the commissioning and operation of the German Heavy Ion Therapy Project a quality assurance program was developed and successfully applied. The complete radiotherapy process using heavy ions was carefully analyzed and divided into three areas related to beam delivery and control, safety‐interlock system and medical physics issues. In this paper, the medical physics issues are addressed. Since the irradiation with heavy ions is a nonstandard modality, new concepts and ion specific tests were developed. As far as possible, national and international standard specifications for radiotherapy were adopted. For each aspect, a performance characteristic and a corresponding acceptance test were introduced. In addition, test characteristics for the constancy tests were established. For all tests, intervention thresholds and test frequencies were specified. Using the described protocol of acceptance tests, the commissioning was passed successfully. The heavy ion irradiation facility was approved by the governmental authorities on the basis of these test results. During clinical operation, constancy tests are performed at the beginning of each treatment period, in order to maintain the quality found during the acceptance tests. Up to now, 48 patients have been treated within 6 treatment periods of 4 weeks each. The concepts used and the tests developed for the quality assurance program may serve as an example of how to introduce systematically a quality assurance program for a new treatment modality.
Recognition of time-distorted sentences by normal-hearing and cochlear-implant listeners
Authors: Fu Qian-Jie , Galvin John J. , Wang Xiaosong
Published: July 2002

This study evaluated the effects of time compression and expansion on sentence recognition by normal-hearing (NH) listeners and cochlear-implant (CI) recipients of the Nucleus-22 device. Sentence recognition was measured in five CI users using custom 4-channel continuous interleaved sampler (CIS) processors and five NH listeners using either 4-channel or 32-channel noise-band processors. For NH listeners, recognition was largely unaffected by time expansion, regardless of spectral resolution. However, recognition of time-compressed speech varied significantly with spectral resolution. When fine spectral resolution (32 channels) was available, speech recognition was unaffected even when the duration of sentences was shortened to 40% of their original length (equivalent to a mean duration of 40 ms/phoneme). However, a mean duration of 60 ms/phoneme was required to achieve the same level of recognition when only coarse spectral resolution (4 channels) was available. Recognition patterns were highly variable across CI listeners. The best CI listener performed as well as NH subjects listening to corresponding spectral conditions; however, three out of five CI listeners performed significantly poorer in recognizing time-compressed speech. Further investigation revealed that these three poorer-performing CI users also had more difficulty with simple temporal gap-detection tasks. The results indicate that limited spectral resolution reduces the ability to recognize time-compressed speech. Some CI listeners have more difficulty with time-compressed speech, as produced by rapid speakers, because of reduced spectral resolution and deficits in auditory temporal processing.
A linear relation between the compressibility and density of blood
Authors: Wang S. H. , Lee L. P. , Lee J. S.
Published: July 2002

By considering the blood as a mixture of ultrafiltrate and protein concentrate, the additive nature of compressibility and density from the components is utilized to deduce a linear relation between the compressibility and density for blood. This deduction also indicates that the intercept and slope of the linear relation are independent of the hematocrit, plasma protein concentration, and hemoglobin concentration of red blood cells. To verify experimentally this linear relation, saline and plasma dilutions on porcine or canine blood flowing in an extracorporeal circuit were carried out. The hematocrit of the experiments ranges from 0% to 55% and the plasma protein concentration ranges from 10 to 90 g/l. A resonance device in the circuit measured the density ρb of blood at 37 °C and an ultrasound system measured the sound velocity cb. The range of density is from 1010 to 1060 g/l and that of sound velocity is from 1530 to 1580 m/s. The linear relation that best fits the data of compressibility [computed as (ρbcb2)−1] and density has a correlation coefficient of 0.9978. The linear relation is found to fit well the dependence of compressibility on density derived from the sound velocity data of human, horse, and porcine blood in the literature.